ArticleLiterature Review

Cervical cancer and use of hormonal contraceptives: A systematic review

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Abstract

Human papillomavirus (HPV) is believed to be the most important cause of cervical cancer. Recent studies suggest that long duration use of oral contraceptives increases the risk of cervical cancer in HPV positive women. Results from published studies were combined to examine the relationship between invasive and in situ cervical cancer and duration and recency of use of hormonal contraceptives, with particular attention to HPV infection. 28 eligible studies were identified, together including 12531 women with cervical cancer. Compared with never users of oral contraceptives, the relative risks of cervical cancer increased with increasing duration of use: for durations of approximately less than 5 years, 5-9 years, and 10 or more years, respectively, the summary relative risks were 1.1 (95% CI 1.1-1.2), 1.6 (1.4-1.7), and 2.2 (1.9-2.4) for all women; and 0.9 (0.7-1.2), 1.3 (1.0-1.9), and 2.5 (1.6-3.9) for HPV positive women. The results were broadly similar for invasive and in situ cervical cancers, for squamous cell and adenocarcinoma, and in studies that adjusted for HPV status, number of sexual partners, cervical screening, smoking, or use of barrier contraceptives. The limited available data suggest that the relative risk of cervical cancer may decrease after use of oral contraceptives ceases. However, study designs varied and there was some heterogeneity between study results. Although long duration use of hormonal contraceptives is associated with an increased risk of cervical cancer, the public health implications of these findings depend largely on the extent to which the observed associations remain long after use of hormonal contraceptives has ceased, and this cannot be evaluated properly from published data.

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... These studies are limited, and the link between IUD usage and the development of precancerous cervical lesions and cervical cancer remains poorly understood (Smith et al. 2003;Appleby et al. 2007). Themicronucleusassaydetectsmicronuclei, whichserve as a highlysensitive marker of DNA damage. ...
... The existence of a possible relationship between LNG-IUS use and cervical cancer will affect women's health globally. Twolarge meta-analysis studies revealed a low risk of cervical cancer associated with IUD use (Castellsagué et al. 2011, Cortessis et al. 2017,while other studies found no relationship between IUD use and cervical cancer (Curtis et al. 2007;Lassise et al. 1991;Roura et al. 2016;Sandmire et al. 1976;Smith et al. 2003). These studies were limited because IUD exposure has never been classified. ...
... For these reasons, presumably, the authors wanted to draw attention to the smear findings. Some studies highlight the relationship between LNG-IUS and cancer (Loopik et al. 2020;Roura et al. 2016;Smith et al. 2003). Authors may also focus on this potential relationship due to the aforementioned concerns. ...
Preprint
Purpose: This study aimed to determine whether any relationships exist between the levonorgestrel-releasing intrauterine system (LNG-IUS) and micronuclei or other nuclear anomalies, including condensed chromatin, karyorrhexis, and karyolysis, on the cervical epithelium in young women. Methods: A prospective observational study was conducted. The study population comprised healthy women aged ≤40 years who were referred for birth control. Cervical smears that were obtained from 18 women before and three months after LNG-IUS insertion were tested for micronuclei and other nuclear anomaliesusing the micronucleus test. Results: The results revealed no statistically significant difference (P>0.05) in the frequency of micronucleated exfoliated cervical mucosa cells after LNG-IUS exposure. However, LNG-IUS was able to increase other nuclear alterations closely related to cytotoxicity. Conclusions: Data indicated that exposure to LNG-IUS may not be a factor in inducing chromosomal damage, but it can promote cytotoxicity.
... The link between cervical cancer and sexually transmitted diseases (STDs) has been well established. The long-term use of hormonal oral contraceptives is associated with increased risk (Smith et al., 2003). Furthermore, having multiple children has been shown to increase risk (Lukac et al., 2018), particularly in women previously infected with HPV. ...
... Specifically, the age of a patient and the number of years of hormonal contraceptive use seem to be important risk factors, agreeing with previous studies. From Figure 7, the women who took hormonal contraceptives for eight or more years appear to have a higher risk cervical cancer, which is in agreement with the findings of Smith et al. (2003). Surprisingly, as seen in Figure 6, Dx.HPV (i.e., whether the patient has had a previous diagnosis of HPV) was ranked to have middling importance, despite the known link between HPV and cervical cancer. ...
Preprint
Variable importance, interaction measures, and partial dependence plots are important summaries in the interpretation of statistical and machine learning models. In this paper we describe new visualization techniques for exploring these model summaries. We construct heatmap and graph-based displays showing variable importance and interaction jointly, which are carefully designed to highlight important aspects of the fit. We describe a new matrix-type layout showing all single and bivariate partial dependence plots, and an alternative layout based on graph Eulerians focusing on key subsets. Our new visualizations are model-agnostic and are applicable to regression and classification supervised learning settings. They enhance interpretation even in situations where the number of variables is large. Our R package vivid (variable importance and variable interaction displays) provides an implementation.
... Our findings showed that other factors such as history of multiple partners and hormonal contraceptive use also play an important role in the increased risk of HPV infection. These factors are also reported by studies on HPV risk in the general female population [2,65,66]. In fact, younger people and those with multiple partners tend to be more vulnerable to sexually transmitted infections as a whole. ...
... In fact, younger people and those with multiple partners tend to be more vulnerable to sexually transmitted infections as a whole. Additionally, studies have suggested that the use of hormonal contraceptives may be associated with increased risk of HPV infection and the development of cervical lesions, including cancer [66][67][68][69]. ...
Article
Objective We systematically investigated the prevalence of HPV, high-risk HPV and its genotype in women living with human immunodeficiency virus (WLHIV) in Brazil. Methods A systematic search was performed up to December 15, 2020. We included studies that used molecular methods for HPV detection in cervical samples and reported the prevalence of HPV in Brazilian WLHIV. The pooled prevalence of HPV, high-risk HPV (HR HPV) and HPV types and their 95% confidence interval (CI) were estimated. Subgroup analyses and meta-regression were conducted. Results A total of 37 studies accounting for 8,436 WLHIV were included. The pooled HPV prevalence was 62% (95%CI 55–68%; I²=96.98%; P <0.001). The pooled prevalence of high-risk HPV was 40% (95%CI, 54–68%; I²=94.23%; P <0.001). We found a wide variety of high-risk HPV genotypes. The high-risk HPV types most reported were HPV 16 (16%) and HPV 58 (6%). We found an increasing ratio of positivity from normal cervix to cancer. There were different factors associated with high-risk HPV, with low CD4+ count the most frequent. Conclusion The increase in the ratio of high-risk HPV positivity from normal cervix to carcinogenic lesions highlights the need to implement well-established testing for high-risk HPV in this population.
... Technological Forecasting & Social Change 162 (2021) 120375 found that smoking may influence the risk of progression from cervical HPV infection to cervical malignancy (Roura et al., 2014). Prolonged use of oral contraceptives increases the risk of cervical cancer amongst HPV positive women (Moreno et al., 2002;Smith et al., 2003). While these studies serve as useful references to treat cervical cancer, it remains unclear whether the reported risk factors are independent risk factors or whether they may act as cofactors to HPV infection in cervical carcer (Kjellberg et al., 2000). ...
... Regarding cervical cancer, various causal factors have been studied individually (Bailey et al., 2016;Bosch et al., 1992;Moreno et al., 2002;Plummer et al., 2003;Smith et al., 2003). However, how the co-occurrence of two or more factors affects the chance of cervical malignancy remains unclear (Kjellberg et al., 2000). ...
Article
The digitalisation in healthcare opens opportunities for more effective chronic disease management. Digitalised medical records are valuable data sources for identifying high-risk patients and facilitating early clinical intervention. However, the liberation of data has plagued adoption amongst physicians as massive data mean more difficult to identify important knowledge from the data. In the cervical cancer context, many patients are adherence to prescription medications only when symptoms appear, beyond the earlier point-in-time of the disease progression. Regular screening is the only way to detect abnormal cells that may develop into cancer if left untreated. Yet, without a comprehensive understanding of the relationship between risk factors and healthcare outcomes, inappropriate screening procedures may be conducted, lengthening the treatment process. Delay in the treatment process may have an irreversible influence on patients’ conditions as chronic diseases progress. This study demonstrates a data-mining framework which extracts knowledge that can advance cervical cancer screening processes in the form of association rules and improves the generalisation potential of the rules for deployment. The knowledge discovered serves as an additional supplement for physicians’ experience and uncovers appropriate screening strategies based on patients’ risk factors, increasing the chances of high-risk patients getting treated for cervical pre-cancers.
... Among them are early onset of sexual activity, multiple sex partners, parity, marital status, socioeconomic status, factors that influence persistent infection (genetics, sex hormones, immunological impairment as in human immunodeficiency virus (HIV) infection, sexually transmitted diseases (HPV, HIV, Herpes simplex virus [HSV], Chlamydia), factors related to HPV (genotype, numbers of viral copies), long term use of hormonal contraception, smoking and obesity. [2][3][4][5][6][7][8][9][10][11][12][13] HPV is very important risk factor necessary for development of cervical dysplasia and cancer. [14][15] After initiation of sexual activity, almost all women acquire infection with HPV. ...
Article
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Background The aim of the study was to evaluate if artificial neural networks can predict high-grade histopathology results after conisation from risk factors and their combinations in patients undergoing conisation because of pathological changes on uterine cervix. Patients and methods We analysed 1475 patients who had conisation surgery at the University Clinic for Gynaecology and Obstetrics of University Clinical Centre Maribor from 1993–2005. The database in different datasets was arranged to deal with unbalance data and enhance classification performance. Weka open-source software was used for analysis with artificial neural networks. Last Papanicolaou smear (PAP) and risk factors for development of cervical dysplasia and carcinoma were used as input and high-grade dysplasia Yes/No as output result. 10-fold cross validation was used for defining training and holdout set for analysis. Results Baseline classification and multiple runs of artificial neural network on various risk factors settings were performed. We achieved 84.19% correct classifications, area under the curve 0.87, kappa 0.64, F-measure 0.884 and Matthews correlation coefficient (MCC) 0.640 in model, where baseline prediction was 69.79%. Conclusions With artificial neural networks we were able to identify more patients who developed high-grade squamous intraepithelial lesion on final histopathology result of conisation as with baseline prediction. But, characteristics of 1475 patients who had conisation in years 1993–2005 at the University Clinical Centre Maribor did not allow reliable prediction with artificial neural networks for every-day clinical practice.
... Squamous cell carcinoma is not considered to be a hormone-dependent tumour, although the presence of ER and PR receptors was indicated in the uterine cervix [63]. Moreover, the long-term use of oral contraception increases the risk of cervical cancer [64]. ...
Article
Full-text available
Sudden cessation of ovary activity as a result of bilateral oophorectomy or chemo- or radiotherapy in premenopausal women is linked with more serious consequences that bear no comparison to natural menopause – to name just a few: higher rate of mortality, higher rate of colorectal and lung cancer, circulatory system diseases, cognitive disorders, Parkinson’s disease, psychological disorders, osteoporosis, and sexual disorders. The prolonged period of estrogens deficit in premenopausal age is connected with worsened quality of life. The progress in oncological care means that in many malignant diseases, also in the case of gynaecological malignancies, the percentage of survivors increases. This makes improving the quality of life more and more important. The purpose of this review is to establish, based on EBM data, the answer to whether replacement hormonal therapy, being the most effective treatment of menopause symptoms, can be recommended for women who have undergone bilateral oophorectomy because of gynaecological cancer. On the basis of collected data, derived from meta-analysis, and studies which have been published within the last 20 years, it seems that the use of the appropriate type of hormonal replacement therapy (HRT) in properly selected gynaecological cancer survivors (epithelial ovarian cancer – EOC, endometrial cancer, squamous cell carcinoma of the cervix) is safe and effective. It seems that benefits connected with better quality of life that stem from the use of appropriate HRT in gynaecological cancer survivors predominate the unfounded fear of disease recurrence in selected patients’ groups.
... Various side effects have been reported because of using oral contraceptives, including headache, nausea, breast tenderness, vaginal dryness, loss of libido, weight gain, irritability, and depression [17,18]. Some studies reported that the use of combined oral contraceptives is associated with an increased risk of breast cancer due to the carcinogenic nature of estrogen-progesterone contraceptives [19], cervical cancer [20], venous thromboembolism [21], and HIV [22,23]. Hence, due to the adverse effect of combined oral contraceptives, there is an immense need to focus on herbal analogs of these contraceptives, which can provide safe and effective contraception. ...
Article
Full-text available
While contraceptive drugs have enabled many people to decide when they want to have a baby, more than 100 million unintended pregnancies each year in the world may indicate the contraceptive requirement of many people has not been well addressed yet. The vagina is a well-established and practical route for the delivery of various pharmacological molecules, including contraceptives. This review aims to present an overview of different contraceptive methods focusing on the vaginal route of delivery for contraceptives, including current developments, discussing the potentials and limitations of the modern methods, designs, and how well each method performs for delivering the contraceptives and preventing pregnancy.
... 1 Depot medroxyprogesterone acetate or CHC use for 5 years or longer may increase the risk for carcinoma in situ and invasive cervical cancer in the setting of persistent human papillomavirus. 44 Limited evidence suggests that the implant does not increase risk. 1 Invasive cervical cancer may be reduced by 30% in women who have used IUCs. 45 Endometrial Cancer/Endometrial Hyperplasia or Endometrial Intraepithelial Neoplasia Endometrial cancer is on the rise in the United States with lifetime risk 3.1%. ...
Article
Women have the opportunity to meet personal contraceptive goals with convenient, highly reliable, and easily reversible methods. Long-acting reversible contraception represents an increasingly popular option for most women throughout the reproductive lifespan. Nonetheless, many women and their health care providers are challenged by coexisting medical issues. We aim to help clinicians individualize contraception and use shared decision-making to enhance patient satisfaction and continuation with their method.
... The main reason of poor prognosis in patients with CC is distant metastasis and lymph node metastasis. Early screening technology has led to reduced mortality in CC patients, but even in early CC, tumor metastasis leads to negative effect and results in about 40% of 5-year survival rate [4,5]. Therefore, it is important to exploit the underlying biological mechanisms of the disease. ...
Article
Full-text available
Objective: High mobility group box 3 (HMGB3) plays an important role in the development of various cancer. This study aims to explore whether HMGB3 regulates cervical cancer (CC) progression and elucidate the underlying mechanism. Methods: HMGB3 expression in clinical patients' tumor samples were determined by real-time quantitative polymerase chain reaction (qRT-PCR) and western blot. HMGB3 overexpression/knockdown were used to investigate its function. Cell apoptosis and cycle were detected by Annexin V/PI staining and flow cytometry. In vivo tumor model was made by subcutaneous injection of HeLa cells transfected with shRNAs targeting HMGB3 (sh-HMGB31) into the flank area of nude mice. Western blot was used to detect the levels of β-catenin, c-Myc, and matrix metalloproteinase-7 (MMP-7) in Hela and CaSki cells transfected with sh-HMGB3 or shRNAs targeting β-catenin. Results: Both messenger RNA and protein levels of HMGB3 were upregulated in CC tissues from patients. High expression level of HMGB3 had positive correlation with serosal invasion, lymph metastasis, and tumor sizes in CC patient. Functional experiments showed that HMGB3 could promote CC cell proliferation both in vitro and in vivo. The expression levels of c-Myc and MMP-7 were increased, resulting in regulating cell apoptosis, cell cycle, and activating Wnt/β-catenin pathway. Conclusions: Our data indicated that HMGB3 may serve as an oncoprotein. It could be used as a potential prognostic marker and represent a promising therapeutic strategy for CC treatment.
... HPV transmission can be reduced through the use of condoms [15]. Some studies have reported that smoking [16], multiparity [17], and long-term use of oral contraceptives [18] can double or triple the risk of precancer and cancer among women infected with carcinogenic types of HPV. There are two major kinds of anti-HPV vaccines approved for use to protect newly sexually active individuals against some of the most common HPV types and boost immunity, namely, therapeutic vaccines and prophylactic vaccines [7]. ...
Article
We formulate a mathematical model to explore the transmission dynamics of human papillomavirus (HPV). In our model, infected individuals can recover with a limited immunity that results in a lower probability of being infected again. In practice, it is necessary to revaccinate individuals within a period after the first vaccination to ensure immunity to HPV infection. Accordingly, we include vaccination and revaccination in our model. The model exhibits backward bifurcation as a result of imperfect protection after recovery and because the basic reproduction number is less than one. We conduct sensitivity analysis to identify the factors that markedly affect HPV infection rates and propose an optimal control problem that minimizes vaccination and screening cost. The optimal controls are characterized according to Pontryagin's maximum principle and numerically solved by the symplectic pseudospectral method.
... HPV transmission can be reduced through the use of condoms [15]. Some studies have reported that smoking [16], multiparity [17], and long-term use of oral contraceptives [18] can double or triple the risk of precancer and cancer among women infected with carcinogenic types of HPV. There are two major kinds of anti-HPV vaccines approved for use to protect newly sexually active individuals against some of the most common HPV types and boost immunity, namely, therapeutic vaccines and prophylactic vaccines [7]. ...
... Aunque el uso prolongado de anticonceptivos hormonales es uno de los factores de riesgo de cáncer de cérvix(83,84), y teniendo en cuenta que en el estado español hasta el 75% de las mujeres de entre 18 y 65 años se han realizado una citología en los últimos 3 años (85), la realización rutinaria de citologías en el momento de la consulta anticonceptiva no estaría indicada(82), aunque puedan ser una oportunidad para valorar la adherencia a los programas de cribado.En cuanto a los dispositivos intrauterinos es necesario destacar que los criterios de elegibilidad para el uso de anticonceptivos establecen algunas contraindicaciones para las mujeres con cáncer de cérvix (4).En el caso de las mujeres con alto riesgo o con una ITS establecida y en las mujeres con alto riesgo de VIH o con una infección por VIH, existen contraindicaciones para la inserción de dispositivos intrauterinos (4). En el caso del VIH, aunque existen anticonceptivos indicados para las mujeres con riesgo de VIH o con una infección por VIH, es importante aconsejar el uso del preservativo de manera adicional.Aunque no existen estudios que hayan comparado el riesgo de enfermedad inflamatoria pélvica (EIP) en mujeres con una ITS dependiendo de si usaban un DIU o no, una revisión sistemática valoró los resultados de seis estudios observacionales en los que compararon los resultados de usuarias de DIU de cobre dependiendo de si tenían una ITS o no en el momento de la inserción(86). ...
... Consistent finding was reported by one systematic review study which revealed that women who have used oral contraceptives for 5 or more years have a higher risk of cervical cancer than women who have never used oral contraceptives. This means, the longer a woman uses oral contraceptives, the greater the increase in her risk of cervical cancer (Smith et al., 2003). Similar findings were observed by Schemik (2008), who said that long term use of oral contraceptives may lead to a more frequent persistence of HPV. ...
Article
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Cervical cancer is the most common and lethal form of cancer occurring among women of subSaharan Africa and Ethiopia. Despite its wider occurrence, cervical cancer is preventable and curable if it is diagnosed and treated in its pre-cancerous stage. Recognizing the risk factors associated with precervical cancer lesion is important to design appropriate strategies for prevention of cervical cancer.However, studies on risk factors associated with pre-cervical cancer lesion in women are limited in Ethiopia as well as in the study location. A hospital based unmatched case control study was conducted at Hawassa university, Comprehensive Specialized Hospital. Bivariate logistic regression analysis was conducted to assess the strength of association between the outcome and explanatory variables. Association was declared when p-value is < 0.05. Predictive variables whose P-value is <0.25 in crude analysis were included in the final multivariate analysis. A backward stepwise approach was conducted and statistically significant association was declared based on adjusted odd ratio (AOR), 95% confidence interval (CI) and P-value <0.05. Findings from multivariate analysis showed contraceptive use [AOR: 5.16, CI (2.97-8.96)], pattern of irregular menstrual bleeding [AOR: 6.03, CI(3.40-10.69)], history of STI [AOR: 4.02, CI (2.28-7.10)] and HIV/AIDS reactive status [AOR: 7.41, CI (4.38- 12.56)] were found to be independent predictors of pre- cervical cancer lesion. Being using contraceptive, having STI history, having irregular menstrual bleeding pattern and having HIV/AIDS reactive status increase the risk of developing pre-cervical cancer. These high risk groups should be encouraged to have regular screening for pre-cervical cancer. Key words: Pre-cervical cancer, visual inspection with acetic acid (VIA), risk factors, cervical cancer.
... 36 The use of exogenous estrogen therapy is a risk factor known in the literature for both adenoid and cervical carcinoma. 37 Exposure to estrogens is implicated not only in the metaplasia process, but also in the particular susceptibility of the transformation zone to the evolution of neoplastic lesions. 38 Unlike what we know for cervical squamous carcinoma, smoking does not appear to be a risk factor for adenocarcinoma, which can be seen in our study, since only 4 (13%) patients were smokers or former smokers. ...
Article
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Objective To observe if the histopathological result of a conization performed after cervical adenocarcinoma in situ diagnosis is compatible with the histopathological analysis of a subsequent hysterectomy. Methods The present descriptive and observational research consisted of the analysis of the medical records of 42 patients who were diagnosed with in situ adenocarcinoma postconization. The analysis consisted of whether there was compatibility between the histopathological reports of conization and hysterectomy and if there was an association between adenocarcinoma in situ and another neoplasia (squamous disease). Interpretation of any immunohistochemistry reports obtained was also performed. In addition, clinical and epidemiological data were also analyzed. Results A total of 42 conizations were performed, 33 (79%) were cold knife conizations and 9 (21%) were loop electrosurgical excision procedures (LEEPs). Of the patients analyzed, 5 (10%) chose not to undergo subsequent hysterectomy to preserve fertility or were < 25 years old. Out of the 37 patients with adenocarcinoma in situ who underwent subsequent hysterectomy, 6 (16%) presented with residual disease. This finding proved incompatible with the finding of the conizations, which had ruled out invasive cancer. Conclusion The prevalence of adenocarcinoma in situ increased in the past years. There is still a large part of the medical literature that advocates the use of conservative treatment for this disease, even though it is common knowledge that it is a multifocal disease. However, the majority of studies advocate that hysterectomy should remain the preferred treatment for women who have already completed their reproductive purpose.
... Family planning options · Pearl Index · Combined oral contraceptives · Contraindication · Thrombotic risk nicht relevant. Eine Invasion des HP-Virus scheint durch die Einnahme von KOK erleichtert zu sein [18,19]. ...
Article
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Zusammenfassung Die Frage nach sicheren kontrazeptiven Maßnahmen stellt sich häufig im gynäkologischen Alltag. Aufgrund der Fülle an effektiven kontrazeptiven Methoden muss die geeignete Maßnahme für jeden einzeln bestimmt werden. Kombinierte orale Kontrazeptiva (KOK) sind aufgrund ihrer Benutzerfreundlichkeit und ihrer Sicherheit eine häufig verschriebene und akzeptierte Form der Kontrazeption. Die klassische Pille besteht aus einem Östrogen- und Gestagenanteil. Durch den Östrogenanteil ergibt sich ein erhöhtes Risiko für kardiovaskuläre Komplikationen. Gerade bei Patientinnen mit Vorerkrankungen ist wegen eines erhöhten Risikos bezüglich kardiovaskulärer Komplikationen bei der Verschreibung von hormonellen kontrazeptiven Maßnahmen ein genaues Hinschauen notwendig und gegebenenfalls auf eine andere Kontrazeption auszuweichen. Dabei ist das Wissen über die Kontraindikationen sowie einflussreiche Risikofaktoren entscheidend. Je größer das Risiko für ein kardiovaskuläres Ereignis eingestuft wird, desto eher wird man eine Östrogengabe vermeiden wollen. Im Folgenden werden das Prinzip der kombinierten oralen Kontrazeption dargestellt, die Kontraindikationen präsentiert, Risikopatienten definiert und anhand von einigen Beispielen ein Plan für eine risikoarme Kontrazeption erstellt.
... In Ethiopia and Kenya, women with longterm use of oral contraceptives were associated with an increased risk of cervical cancer compared to women who do not use oral contraceptives [50,57]. A meta-analysis study of 28 case-control studies concluded that long-term use of oral contraceptive is an important risk factor of cervical cancer [58]. Moreover, an animal model study indicated that mouse treated with longer duration of estrogen developed cervical cancer than mouse treated with short duration of estrogen [59]. ...
... Several epidemiological studies and a systematic review published in 2003 reported an association between HPVrelated cervical cancer and use of COCs; the data was not confirmed in a recent meta-analysis, suggesting that this association is related to the fact that condoms are seldom used in patients on CHCs, with a consequent higher incidence of HPV infections [47][48][49][50][51][52][53][54][55][56]. ...
Article
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Even though fertility is reduced, conception and delivery are possible in all stages of CKD. While successful planned pregnancies are increasing, an unwanted pregnancy may have long-lasting deleterious effects, hence the importance of birth control, an issue often disregarded in clinical practice. The evidence summarized in this position statement is mainly derived from the overall population, or other patient categories, in the lack of guidelines specifically addressed to CKD. Oestroprogestagents can be used in early, non-proteinuric CKD, excluding SLE and immunologic disorders, at high risk of thromboembolism and hypertension. Conversely, progestin only is generally safe and its main side effect is intramestrual spotting. Non-medicated intrauterine devices are a good alternative; their use needs to be carefully evaluated in patients at a high risk of pelvic infection, even though the degree of risk remains controversial. Barrier methods, relatively efficacious when correctly used, have few risks, and condoms are the only contraceptives that protect against sexually transmitted diseases. Surgical sterilization is rarely used also because of the risks surgery involves; it is not definitely contraindicated, and may be considered in selected cases. Emergency contraception with high-dose progestins or intrauterine devices is not contraindicated but should be avoided whenever possible, even if far preferable to abortion. Surgical abortion is invasive, but experience with medical abortion in CKD is still limited, especially in the late stages of the disease. In summary, personalized contraception is feasible, safe and should be offered to all CKD women of childbearing age who do not want to get pregnant.
... Findings indicated that HPV is a necessary cause of cervical cancer; this means that the other risk factors can increase the risk of cervical cancer, but they are not able to develop this kind of cancer in the absence of HPV [5]. In this regard, potential cofactors involved in the cervical cancer pathogenesis are divided into three classes: 1) Environmental risk factors such as using hormonal birth control [6,7], smoking [8], parity (the number of sex partners) [9], and have a history of being infected with other sexually transmitted agents [10][11][12]. ...
Article
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Cervical cancer is the fourth-ranked cancer in the world and is associated with a large number of deaths annually. Chemotherapy and radiotherapy are known as the common therapeutic approaches in the treatment of cervical cancer, but because of their side effects and toxicity, researchers are trying to discovery alternative therapies. Beta-glucans, a group of glucose polymers that are derived from the cell wall of fungi, bacteria, and etc. it has been showed that beta-glucans have some anti-cancer properties which due to their impacts on adaptive and innate immunity. Along to these impacts, these molecules could be used as drug carriers. In this regard, the application of beta-glucans is a promising therapeutic option for the cancer prevention and treatment especially for cervical cancer. Herein, we have summarized the therapeutic potential of beta-glucans alone or as adjuvant therapy in the treatment of cervical cancer. Moreover, we highlighted beta-glucans as drug carriers for preventive and therapeutic purposes.
... Results such as age, beginning of active sexual life, number of sexual partners, promiscuity, number of vaginal deliveries, condom use, smokers, cervical injury, history of sexually transmitted infections, use of hormonal contraceptives were not associated with infection of human papillomavirus in our study. Other studies have found an association between HPV and these factors (23)(24)(25)(26)(27)(28)(29) . Sathian et al. and Bosch et al. mention that promiscuity and the number of sexual partners are factors of HPV infection (30,31) and the study by Francheschi et al. mentions that there is a relationship between HPV infection and the age of first sexual intercourse (32) . ...
Article
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Background: Human papillomavirus is cause of cervical cancer, one of the most common cancers among women. Objective: To determine the prevalence of human papillomavirus and associated factors in patients with unknown cytology. Methods: In gynecology patients with unknown cytology attended at Lambayeque Regional Hospital, at the northern coast of Peru, from April through June 2019, DNA extraction for human papillomavirus identification performed on cervical samples was based on the salting out method. Samples were processed by polymerase chain reaction. All samples were amplified for MY09 and MY11 primers, and PC04 / GH20 primers. Bivariate analysis used the chi-square and t-student tests. Results: 29.9% of the patients studied were infected with human papillomavirus. No statistically significant difference was found between human papillomavirus infection and age, age at first sexual intercourse, promiscuity, number of vaginal deliveries, cervical lesion, history of sexually transmitted infections, use of hormonal contraceptive or condoms, and smoking.
... Cervical cancer is the third most common gynaecological cancer and can be differentiated into squamous cell and adenocarcinoma. Due to the association of the combined oral contraceptive pill in the development of adenocarcinomas, 19 concerns have been raised on the use of HRT for survivors of cervical cancer. While one multicentre case-control study demonstrated a positive but not a significant association in the use of estrogen-only HRT with adenocarcinoma but not with squamous carcinoma, 20 there is limited data beyond this study. ...
Article
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Objective The aim of this study was to identify prescribing patterns at a specialist menopause service in a central London teaching hospital for women following treatment for a malignancy. Study design This was a prospective cohort study with data collected over a seven-month period from December 2019 to June 2020. All women reviewed at the specialist menopause services following treatment of a malignancy, BRCA carriers and Lynch syndrome were included in the study, with management options divided into three categories: hormonal, non-hormonal and no treatment. Main outcome measures The primary outcome of this study was to identify prescribing patterns for all women reviewed following a diagnosis of a malignancy, as well as those with genetic mutations necessitating risk-reducing prophylactic bilateral salpingo-oopherectomy (BSO). Results Altogether 71 women were included in this study, with the majority of women post management of a non-gynaecological malignancy (51/71, 72%), of which breast cancer was the most common (37/71, 52%). While non-hormonal treatment was the most popular among those treated for breast cancer, for all other malignancies, hormonal treatment was more widespread. Fourteen women also had genetic mutations, with all of these women commencing hormonal treatment post risk reducing surgery. Conclusion With the exception of those with a history of hormone-sensitive breast cancer, the use of hormonal treatment for menopausal symptoms remained widespread. While this was a relatively small study, the need for long-term follow-up across specialist menopause services, to assess the risk of recurrence is vital.
... Although hormonal contraception is highly effective, it does not fulfill the needs of all women. Hormonal contraceptives can have a myriad of side effects such as irregular bleeding, weight gain, pulmonary embolism, and increased risk for cervical and breast cancer [139,140]. These side effects, along with misconceptions of infertility caused by hormonal contraceptives, are driving forces to their discontinuation [141]. ...
Article
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There is a high global prevalence of HIV, sexually transmitted infections (STIs), and unplanned pregnancies. Current preventative daily oral dosing regimens can be ineffective due to low patient adherence. Sustained release delivery systems in conjunction with multipurpose prevention technologies (MPTs) can reduce high rates of HIV/STIs and unplanned pregnancies in an all-in-one efficacious, acceptable, and easily accessible technology to allow for prolonged release of antivirals and contraceptives. The concept and development of MPTs have greatly progressed over the past decade and demonstrate efficacious technologies that are user-accepted with potentially high adherence. This review gives a comprehensive overview of the latest oral, parenteral, and vaginally delivered MPTs in development as well as drug delivery formulations with the potential to advance as an MPT, and implementation studies regarding MPT user acceptability and adherence. Furthermore, there is a focus on MPT intravaginal rings emphasizing injection molding and hot-melt extrusion manufacturing limitations and emerging fabrication advancements. Lastly, formulation development considerations and limitations are discussed, such as nonhormonal contraceptive considerations, challenges with achieving a stable coformulation of multiple drugs, achieving sustained and controlled drug release, limiting drug–drug interactions, and advancing past preclinical development stages. Despite the challenges in the MPT landscape, these technologies demonstrate the potential to bridge gaps in preventative sexual and reproductive health care.
... A meta-analysis by the International Collaboration of Epidemiological Studies of Cervical Cancer et al. from 2007 of individual data from 24 epidemiologic studies found that among current oral contraceptive (OC) users, the risk of invasive cervical cancer increased with duration of use (adjusted odds ratio, aOR = 1.90, 95% CI 1.69, 2.13, for individuals with 5 or more years of use compared to never users) [7] , suggesting that OCs may promote HPV-induced carcinogenesis. However, the extent to which these findings are affected by confounding factors, such as sexual and lifestyle behaviors including frequency of screening, is not clear [8] . Further, these studies did not differentiate between COCs and progestin-only OCs [ 5 , 7 ], and the extent to which other hormonal contraceptives (HC) affect risk of progression of hrHPV infection to cervical dysplasia/cancer is also not clear. ...
Article
Objective Studies on the effect of long-term use of combined oral contraceptives (COCs) on cervical dysplasia and/or cancer risk have been inconsistent. Less is known about the effects of other forms of hormonal contraception (HC). We examine whether HC use increases the risk of incident cervical intraepithelial neoplasia (CIN) 2, 3 and/or cancer after accounting for preexisting human papillomavirus (HPV) infection. Study Design Systematic review of prospective studies on HC use as risk factor for cervical dysplasia with HPV infection documented prior to outcome assessment including PubMed and EMBASE records between January 2000 and February 2020 (Prospero #CRD42019130725). Results Among 9 eligible studies, seven described recency and type of HC use and therefore comprise the primary analysis; two studies limit comparisons to ever versus never use and are summarized separately. All seven studies explored the relationship between oral contraceptive (OC) use and cervical dysplasia/cancer incidence: two found increased risk (adjusted odds ratio, aOR=1.5-2.7), one found no association but decreased risk when restricted to women with persistent HPV (adjusted hazard ratio=0.5), and four found no association. None of the seven studies differentiated between COC and progestin-only pills (POPs) by use recency or duration. The only study that included injectable progestin-only contraception (DMPA) found increased CIN3 incidence among current versus never users (aOR=1.6). The one study that included Norplant found no association. Two studies included intrauterine device (IUD) use, but did not differentiate between hormonal and copper IUDs, and found no association. Conclusion We found no consistent evidence that OC use is associated with increased risk for cervical dysplasia/cancer after controlling for HPV infection. There were too few studies of progestin-only injectables, implants or IUDs to assess their effect on cervical dysplasia/cancer risk. Implications Use of single self-reported HC measures and insufficient distinction by hormonal constituent cloud our understanding of whether some HCs increase risk for cervical cancer. Methodologically rigorous studies with distinct HCs measured as time-varying exposures are needed to inform cervical cancer prevention efforts and improve our understanding of cervical cancer etiology.
... Расчет отношения шансов (ОШ) показал, что прием КОК в течение 5 лет и более приводит к 4-кратному повышению риска РШМ среди женщин с положительным результатом на ДНК ВПЧ. В другом исследовании показано повышение риска на 10% при использовании КОК менее 5 лет, на 60% -в течение 5-9 лет и отмечено удвоение риска при использовании в течение 10 лет и более [36]. Это, безусловно, определяет необходимость тестирования пользователей КОК на ДНК ВПЧ [37] и динамичного наблюдения за состоянием шейки матки. ...
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Despite all prevention and education campaigns, the rate of unintended pregnancies is 40% of the more than 200 million pregnancies occurring worldwide. About half of them end in abortion. Women in the 2030 age group, where abortions peak, have not yet fulfilled their reproductive plans. The lack of competent post-abortion rehabilitation for women, including contraception counselling, results in one in three choosing a less effective method, and one in four not using any contraceptive methods at all. According to the The World Health Organization Guidelines for Safe Abortion, all women should use hormonal contraception after spontaneous or induced abortion. Combined oral contraceptives (OCs) with 30 mcg ethinyl estradiol in combination with drospirenone, which has strong antigonadotropic activity, can effectively suppress hypothalamic-pituitary-ovarian axis excitability after abortion. OCs can be used to prevent neural tube defects in the case of pregnancy after withdrawal of OCs. The use of folate-containing OCs is a sensible means of folate supplementation in women of reproductive age that may guarantee a future healthy pregnancy and overall health.
... One of the meta-analysis reported that cervical cancer risk increased in the group with more than 5 years of usage, compared with groups with no history of usage (RR 1.9; 95% CI: 1.69-2.13). The risk decreased after stop using; and after 10 years or more, the risk would be the same as the group without history of usage [29][30][31].( [32] Staging is important in determining disease spread, prognosis, management plan, and comparing therapeutic methods. Clinical staging was based on Federation International Of Gynaecology And Obstetrics (FIGO) classification from 2018 [34]. ...
Article
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Cervical cancer mostly caused by Human Papilloma Virus. Staging and therapy have been extensively studied, and highly correlated with the cellular development of oncogenesis. Mutation was caused by E6 and E7 oncoprotein, also inactivation of 2 tumor suppressor factors (pRB and p53). P53 also regulated MMP1, which dysregulation of MMP transcription would promote tumor metastasis, because of its role in extracellular matrix degradation in tumor invasion. Clinical staging of Cervical Cancer was based on Federation International of Gynaecology and Obstetrics (FIGO) classification from 2018. Management was divided into Surgery, Radiotherapy, and Chemotherapy.
... Clinicians should reassure women with endometriosis about the risk of malignancy associated with the use of hormonal contraceptives (Smith et al., 2003;Zucchetto et al., 2009;Gierisch et al., 2013;Havrilesky et al., 2013;Braganza et al., 2014;Berlanda et al., 2016;Wentzensen et al., 2016;Butt et al., 2018;Michels et al., 2018). ...
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Study question: How should endometriosis be diagnosed and managed based on the best available evidence from published literature? Summary answer: The current guideline provides 109 recommendations on diagnosis, treatments for pain and infertility, management of disease recurrence, asymptomatic or extrapelvic disease, endometriosis in adolescents and postmenopausal women, prevention and the association with cancer. What is known already: Endometriosis is a chronic condition with a plethora of presentations in terms of not only the occurrence of lesions, but also the presence of signs and symptoms. The most important symptoms include pain and infertility. Study design size duration: The guideline was developed according to the structured methodology for development of ESHRE guidelines. After formulation of key questions by a group of experts, literature searches and assessments were performed. Papers published up to 1 December 2020 and written in English were included in the literature review. Participants/materials setting methods: Based on the collected evidence, recommendations were formulated and discussed within specialist subgroups and then presented to the core guideline development group (GDG) until consensus was reached. A stakeholder review was organized after finalization of the draft. The final version was approved by the GDG and the ESHRE Executive Committee. Main results and the role of chance: This guideline aims to help clinicians to apply best care for women with endometriosis. Although studies mostly focus on women of reproductive age, the guideline also addresses endometriosis in adolescents and postmenopausal women. The guideline outlines the diagnostic process for endometriosis, which challenges laparoscopy and histology as gold standard diagnostic tests. The options for treatment of endometriosis-associated pain symptoms include analgesics, medical treatments and surgery. Non-pharmacological treatments are also discussed. For management of endometriosis-associated infertility, surgical treatment and/or medically assisted reproduction are feasible. While most of the more recent studies confirm previous ESHRE recommendations, there are five topics in which significant changes to recommendations were required and changes in clinical practice are to be expected. Limitations reasons for caution: The guideline describes different management options but, based on existing evidence, no firm recommendations could be formulated on the most appropriate treatments. Also, for specific clinical issues, such as asymptomatic endometriosis or extrapelvic endometriosis, the evidence is too scarce to make evidence-based recommendations. Wider implications of the findings: The guideline provides clinicians with clear advice on best practice in endometriosis care, based on the best evidence currently available. In addition, a list of research recommendations is provided to stimulate further studies in endometriosis. Study funding/competing interests: The guideline was developed and funded by ESHRE, covering expenses associated with the guideline meetings, with the literature searches and with the dissemination of the guideline. The guideline group members did not receive payments. C.M.B. reports grants from Bayer Healthcare and the European Commission; Participation on a Data Safety Monitoring Board or Advisory Board with ObsEva (Data Safety Monitoring Group) and Myovant (Scientific Advisory Group). A.B. reports grants from FEMaLE executive board member and European Commission Horizon 2020 grant; consulting fees from Ethicon Endo Surgery, Medtronic; honoraria for lectures from Ethicon; and support for meeting attendance from Gedeon Richter; A.H. reports grants from MRC, NIHR, CSO, Roche Diagnostics, Astra Zeneca, Ferring; Consulting fees from Roche Diagnostics, Nordic Pharma, Chugai and Benevolent Al Bio Limited all paid to the institution; a pending patent on Serum endometriosis biomarker; he is also Chair of TSC for STOP-OHSS and CERM trials. O.H. reports consulting fees and speaker's fees from Gedeon Richter and Bayer AG; support for attending meetings from Gedeon-Richter, and leadership roles at the Finnish Society for Obstetrics and Gynecology and the Nordic federation of the societies of obstetrics and gynecology. L.K. reports consulting fees from Gedeon Richter, AstraZeneca, Novartis, Dr KADE/Besins, Palleos Healthcare, Roche, Mithra; honoraria for lectures from Gedeon Richter, AstraZeneca, Novartis, Dr KADE/Besins, Palleos Healthcare, Roche, Mithra; support for attending meetings from Gedeon Richter, AstraZeneca, Novartis, Dr KADE/Besins, Palleos Healthcare, Roche, Mithra; he also has a leadership role in the German Society of Gynecological Endocrinology (DGGEF). M.K. reports grants from French Foundation for Medical Research (FRM), Australian Ministry of Health, Medical Research Future Fund and French National Cancer Institute; support for meeting attendance from European Society for Gynaecological Endoscopy (ESGE), European Congress on Endometriosis (EEC) and ESHRE; She is an advisory Board Member, FEMaLe Project (Finding Endometriosis Using Machine Learning), Scientific Committee Chair for the French Foundation for Research on Endometriosis and Scientific Committee Chair for the ComPaRe-Endometriosis cohort. A.N. reports grants from Merck SA and Ferring; speaker fees from Merck SA and Ferring; support for meeting attendance from Merck SA; Participation on a Data Safety Monitoring Board or Advisory Board with Nordic Pharma and Merck SA; she also is a board member of medical advisory board, Endometriosis Society, the Netherlands (patients advocacy group) and an executive board member of the World Endometriosis Society. E.S. reports grants from National Institute for Health Research UK, Rosetrees Trust, Barts and the London Charity; Royalties from De Gruyter (book editor); consulting fees from Hologic; speakers fees from Hologic, Johnson & Johnson, Medtronic, Intuitive, Olympus and Karl Storz; Participation in the Medicines for Women's Health Expert Advisory Group with Medicines and Healthcare Products Regulatory Agency (MHRA); he is also Ambassador for the World Endometriosis Society. C.T. reports grants from Merck SA; Consulting fees from Gedeon Richter, Nordic Pharma and Merck SA; speaker fees from Merck SA, all paid to the institution; and support for meeting attendance from Ferring, Gedeon Richter and Merck SA. The other authors have no conflicts of interest to declare. Disclaimer: This guideline represents the views of ESHRE, which were achieved after careful consideration of the scientific evidence available at the time of preparation. In the absence of scientific evidence on certain aspects, a consensus between the relevant ESHRE stakeholders has been obtained. Adherence to these clinical practice guidelines does not guarantee a successful or specific outcome, nor does it establish a standard of care. Clinical practice guidelines do not replace the need for application of clinical judgement to each individual presentation, nor variations based on locality and facility type. ESHRE makes no warranty, express or implied, regarding the clinical practice guidelines and specifically excludes any warranties of merchantability and fitness for a particular use or purpose (Full disclaimer available at www.eshre.eu/guidelines.).
... Un grupo pequeño de pacientes era fumadora y usaba anticonceptivos hormonales por largo tiempo (>5 años), estos son factores de riesgo importantes en la infección por VPH (Hellberg & Stendahl, 2005). El uso prologando de anticonceptivos hormonales incrementa el riesgo de una infección persistente de VPH (Smith et al., 2003). Las mujeres fumadoras tienen mayor riesgo de tener CC por una infección persistente de VPH (Hellberg & Stendahl, 2005). ...
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Introduction: human papillomavirus causes cancers in women around the globe. Objective: To determine the prevalence of human papillomavirus in obstetrics and gynecology patients at the Regional Hospital of Lambayeque. Methods: Descriptive study, cross sectional. 187 patients’ samples were analyzed between April and May 2019. Human papillomavirus DNA samples were extracted using the Salting Out method. The Polymerase Chain Reaction technique was used to amplify the viral DNA, using the primers PC04 / GH20 and MY09 / MY11. Descriptive statistics and bivariate analysis were used. Results: a mean of 45 years was found, a mean of a sexual partner and 2 vaginal deliveries, 23 patients with cervical lesions, a history of STIs (5), hormonal contraceptives (135), condom use (177), smoker (22). It was found that 53 had a positive result (29.94 %) and 124 patients were negative for the test (70.06 %), they were infected with the human papillomavirus. No statistical correlation was found for human papillomavirus and age, age of first sexual intercourse, promiscuity, number of vaginal deliveries, cervical lesions, history of sexually transmitted infections (STIs), use of hormonal contraceptives, use of condoms, and smoking. Conclusion: there is a high percentage of the human papillomavirus in patients who are cared for in the OB / GYN area.
... Epithelial cells infected from high-risk human papillomaviruses are associated with cervical cancer [13]. A persistent infection by HPV can be developed by other factors like use of hormonal contraceptives, which can lead to cervical cancer in women [14]. According to International Agency for Research on Cancer (IARC), 12 HPV types (HPV- 16,18,31,33,35,39,45,51,52,56,58 and 59) are referred to as Group 1 human carcinogens and termed as high-risk HPV types [15]. ...
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Cervical cancer has the highest mortality rate worldwide. In the quest for reducing such a high mortality rate, advancements in diagnosis as well as treatment are being undertaken at various scales across the globe. With the recent advancements in the applications of nanotechnology, simple, rapid and inexpensive diagnostic methods for cervical cancer, i.e., human papillomavirus (HPV), especially high-risk oncogenic subtypes 16 and 18 have started to gain attention of health care practitioners. This review outlines the current applications of biosensors for the diagnosis of HPV, as compared to the conventional techniques for measuring HPV that have some limitations. The traditional methods used for cervix cancer are less sensitive, whereas nanotechnology has greatly improved the sensitivity. Due to cancer incidence and mortality growing rapidly worldwide, the prevalence and risk factors are also discussed in this review.
... The progression of CC, from normal cervical mucosal epithelium to cervical intraepithelial neoplasia (CIN) grade 1, 2, and 3, to CC (3) is associated with persistent high-risk human papillomavirus (HPV) infection (4). Furthermore, a number of risk factors, including early sexual activity (5), multiple sexual partners (6), long-term use of oral contraceptives (7), genetic factors [active oncogenes, including PIK3CA (8), ATAD2 (9) and CRNDE (10); tumor suppressor genes, including p53 (11), Ras association domain family 1 isoform A (12) and NOL7 (13)], tobacco use [current smoker, started smoking age ≤15 years, smoking duration ≥30 years, ≥20 cigarettes/day (14)] and other viral infections (such as HIV, herpes simplex virus (HSV) type II and bacterial infections caused by Chlamydia trachomatis) (15) have been associated with CC progression. ...
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Cervical Cancer is one of the leading causes of cancer-associated mortality in women. The present study aimed to identify key genes and pathways involved in cervical cancer (CC) progression, via a comprehensive bioinformatics analysis. The GSE63514 dataset from the Gene Expression Omnibus database was analyzed for hub genes and cancer progression was divided into four phases (phases I-IV). Pathway enrichment, protein-protein interaction (PPI) and pathway crosstalk analyses were performed, to identify key genes and pathways using a criterion nodal degree ≥5. Gene pathway analysis was determined by mapping the key genes into the key pathways. Co-expression between key genes and their effect on overall survival (OS) time was assessed using The Cancer Genome Atlas database. A total of 3,446 differentially expressed genes with 107 hub genes were identified within the four phases. A total of 14 key genes with 11 key pathways were obtained, following extraction of ≥5 degree nodes from the PPI and pathway crosstalk networks. Gene pathway analysis revealed that CDK1 and CCNB1 regulated the cell cycle and were activated in phase I. Notably, the following terms, 'pathways in cancer', 'focal adhesion' and the 'PI3K-Akt signaling pathway' ranked the highest in phases II-IV. Furthermore, FN1, ITGB1 and MMP9 may be associated with metastasis of tumor cells. STAT1 was indicated to predominantly function at the phase IV via cancer-associated signaling pathways, including 'pathways in cancer' and 'Toll-like receptor signaling pathway'. Survival analysis revealed that high ITGB1 and FN1 expression levels resulted in significantly worse OS. CDK1 and CCNB1 were revealed to regulate proliferation and differentiation through the cell cycle and viral tumorigenesis, while FN1 and ITGB1, which may be developed as novel prognostic factors, were co-expressed to induce metastasis via cancer-associated signaling pathways, including PI3K-Art signaling pathway, and focal adhesion in CC; however, the underlying molecular mechanisms require further research.
... Los métodos de planificación familiar han sido uno de los factores más discutidos en el riesgo de aparición de estas lesiones, el más fuertemente asociado es el uso prolongado de anticonceptivos de tipo hormonal (Mendoza et al., 2012;Serrano et al., 2004, Sriamporn et al., 2004Smith et al., 2003;Chih et al., 2014). Un estudio realizado por la International Agency for Research on Cancer, encontró que el uso de anticonceptivos orales durante cinco a diez años o más incrementaba el riesgo de cáncer de cuello uterino (Moreno et al., 2002), otros estudios sugieren que el uso prolongado de anticonceptivos orales puede incrementar hasta dos veces el riesgo de padecer cáncer de cérvix (Cibula et al., 2010;La Vecchia et al., 2014). ...
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En este libro se presentan los resultados originales de investigación obtenidos por el grupo Histopatología, de la Facultad de Medicina de la Universidad de Cartagena, dirigidos por las autoras, en relación con el estudio de la prevención, detección temprana y diagnóstico del cáncer de cuello uterino y sus lesiones precursoras. Inicialmente se hace una contextualización teórica sobre aspectos generales del cáncer de cuello uterino y sus lesiones precursoras, que incluye la patogenia de la enfermedad, su relación con el Virus del Papiloma Humano y los marcadores postulados para mejorar la precisión y reproducibilidad del estudio citológico e histológico de las lesiones. Los capítulos siguientes presentan varios estudios que analizan los factores de riesgo para las lesiones premalignas del cuello uterino, el conocimiento, la actitud y las prácticas en relación a la tamización para su detección temprana, y la adherencia al manejo de las mismas, en el contexto de las mujeres de la región Caribe colombiana. También se analizan los métodos de diagnóstico citológico e histopatológico, junto con marcadores recientemente desarrollados, en relación a su desempeño para el diagnóstico oportuno de las lesiones premalignas del cuello uterino y el reconocimiento preciso de las lesiones potencialmente generadoras de una lesión tumoral invasiva. Por último, para poner en contexto la relevancia del diagnóstico oportuno de estas lesiones en la prevención del cáncer de cuello uterino, se presenta la experiencia acumulada de una entidad de referencia de la región Caribe colombiana en el manejo de un programa de detección temprana de esta neoplasia. Siendo el cáncer de cuello uterino un problema de salud pública que afecta en forma predominante las poblaciones de bajo desarrollo socioeconómico como la nuestra, esta investigación busca aportar evidencias que contribuyan al mejoramiento en la oportunidad de un diagnóstico oportuno y preciso de sus lesiones precursoras que redunde en lograr en forma efectiva la disminución de las cifras de esta enfermedad en nuestras mujeres.
... HPV remains as one of the most prevalent causative agents for cervical cancer (Lowy and Schiller, 1998). Other risk factors attributed to the persistent HPV infection include unsafe sexual practices, smoking habits, and long-term use of oral contraceptives (Smith et al., 2003;Cancer, 2006;Žitkutė and Bumbuliene, 2016). ...
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Background: Cervical cancer is the third leading cause of death in Malaysia, and Human Papilloma Virus (HPV) is the principal aetiology that is responsible for its development. This study was aimed to determine the prevalence and distribution of HPV types among different age groups, ethnicity, and areas in Malaysia. Materials and methods: A total of 764 women aged 20-74 years old within the cities of Johor Bahru, Kuala Lumpur, Ipoh, Penang, and Kota Kinabalu underwent both cervical cytological assessment and HPV DNA analysis. Cervical cytology glass slides were prepared using the liquid base technique (Path TEZT TM). HPV DNA was extracted using TANBead® Nucleic Acid Extraction Kit (Taiwan Advanced Nonotech Inc.), then the types were further identified using a DR.HPV Genotyping IVD kit. Results: The prevalence of HPV infection was 14.0% (107/764) with high-risk type at 10.7% (82/764) and low-risk type at 3.27% (25/764). The most common high-risk HPV types were HPV-52, 66, 33, 39, and 58 whereas low-risk HPV types were HPV-6, 40, and 81. The majority of HPV infections (80.37%) were detected in women with normal cytology results. The most prevalent HPV type among Chinese is 33 (n=6) followed by 16, 44, 58, 66 and 68 (n=5). Among Malays, HPV 16 and 51 were the two most prevalent types (n=2). The sensitivity of the HPV DNA test compared to cytology was 100% with a specificity of 88.37%. Conclusion: This study revealed that the most common high-risk HPV type among women living in urban areas in Malaysia is HPV 52, unfortunately which is not the type of infection the current HPV vaccine is covered for protection among females. These findings may contribute beneficial information to health care providers for the appropriate use of HPV vaccine in the prevention of cervical cancer in Malaysia.
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OTU deubiquitinase 5 (OTUD5), as a member of the ovarian tumor protease (OTU) family, was previously reported to play important roles in DNA repair and immunity. However, little is known about its function in tumors. Cervical cancer is a malignant tumor that seriously endangers the lives of women. Here, we found that low expression of OTUD5 in cervical cancer is associated with poor prognosis. Its expression is associated with tumor stage, metastatic nodes and tumor subtypes such as those related to the phosphatidylinositol–3–kinase (PI3K)–AKT signaling, epithelial-mesenchymal transition (EMT) and hormones. In addtion, we analyzed the coexpressed genes, related miRNAs, transcription factors, kinases, E3s and interacting proteins of OTUD5. We demonstrated that OTUD5 affects the expression levels of WD repeat domain 45 (WDR45), ubiquitin-specific peptidase 11 (USP11), GRIP1 associated protein 1 (GRIPAP1) and RNA binding motif protein 10 (RBM10). Moreover, hsa-mir-137, hsa-mir-1913, hsa-mir-937, hsa-mir-607, hsa-mir-3149 and hsa-mir-144 may inhibit the expression of OTUD5. Furthermore, we performed enrichment analysis of 22 coexpressed genes, 33 related miRNAs and 30 interacting proteins. In addition to ubiquitination and immunology related processes, they also participate in Hippo signaling, insulin signaling, EMT, histone methylation and phosphorylation kinase binding. Our study for the first time analyzed the expression of OTUD5 in cervical cancer and its relationship with clinicopathology and provided new insights for further study of its regulatory mechanism in tumors.
Article
The present study explores the application of the micro-Raman spectroscopy technique to discriminate normal and cervicitis condition from cervical malignancy by analyzing the Raman signatures of tissues and plasma samples of the same subjects. The Raman peaks from tissue samples at 1026 cm⁻¹,1298 cm⁻¹ and 1243 cm⁻¹ are attributed to glycogen, fatty acids and collagen and are found to be reliable signatures capable of identifying cervicitis and normal condition from cervical cancer. The Raman signatures from plasma samples belonging to carbohydrates (578 cm⁻¹), lipids (1059 cm⁻¹) and nucleic acids (1077 cm⁻¹,1341 cm⁻¹ and 1357 cm⁻¹) are quite useful to classify various stages of cervix at par with tissue based diagnosis. The PCA-SVM based classification of the spectral data indicates the potential of Raman spectroscopy based liquid biopsy to rule out false diagnosis of cervicitis as cervical malignancy.
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Objective We assessed the relationship between Chlamydia trachomatis infection, duration of oral contraceptive (OC) use and cervical atypia among young adult Finnish women. Design A longitudinal study. Setting and participants Women who were included in this study participated in a community-randomised trial on the effectiveness of human papillomavirus (HPV) vaccination and C. trachomatis screening at ages 18.5 and 22 years in Finland. They completed questionnaires on both visits about sexual behaviours. The cytology test results at age 18.5 and 22 years were also available for those women. The total number of participants in this study at 18.5 years of age were 11 701 and at 22 years of age were 6618. Main outcome measure ORs with 95% CIs using univariable and multivariable logistic regression were used to assess the association between C. trachomatis infection, duration of OC and squamous intraepithelial lesions (SIL). Results There were 940 cytological SIL cases at the first screening visit and 129 cytological SIL cases at the second screening visit. Among the 22 years old, more than fourfold adjusted risk of SIL was associated with C. trachomatis positivity. The HPV16/18, condom use, smoking and number of sexual partners adjusted joint effect of prolonged OC use and C. trachomatis was significantly increased (OR 4.7, 95% CI 1.7 to 12.8) in the 22-year-old women. This observed joint effect was 1.6 times higher than expected on a multiplicative scale. On additive scale, the observed relative excess risk from interaction was 1.8. Conclusion The risk of SIL in HPV vaccinated women is significantly increased if they are C. trachomatis positive and have used OC for 5 or more years. The biological basis may be lack of condom facilitated protection against sexually transmitted diseases. Trial registration number NCT00534638 .
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Background Human papillomavirus (HPV) infection is one of the most common sexually transmitted infections. However, only a small percentage of high-risk (HR) HPV infections progress to cervical precancer and cancer. In this study, we investigated the role of the cervicovaginal microbiome (CVM) in the natural history of HR-HPV. Methods This study was nested within the placebo arm of the Costa Rica HPV Vaccine Trial that included women aged 18–25 years of age. Cervical samples from two visits of women with an incident HR-HPV infection (n = 273 women) were used to evaluate the prospective role of the CVM on the natural history of HR-HPV. We focus specifically on infection clearance, persistence, and progression to cervical intraepithelial neoplasia grade 2 and 3 (CIN2+). The CVM was characterized by amplification and sequencing the bacterial 16S V4 rRNA gene region and the fungal ITS1 region using an Illumina MiSeq platform. OTU clustering was performed using QIIME2. Functional groups were imputed using PICRUSt and statistical analyses were performed using R. Results At Visit 1 (V1) abundance of Lactobacillus iners was associated with clearance of incident HR-HPV infections (Linear Discriminant Analysis (LDA)>4.0), whereas V1 Gardnerella was the dominant biomarker for HR-HPV progression (LDA>4.0). At visit 2 (V2), increased microbial Shannon diversity was significantly associated with progression to CIN2+ (p = 0.027). Multivariate mediation analysis revealed that the positive association of V1 Gardnerella with CIN2+ progression was due to the increased cervicovaginal diversity at V2 (p = 0.040). A full multivariate model of key components of the CVM showed significant protective effects via V1 genus Lactobacillus, OR = 0.41 (0.22–0.79), V1 fungal diversity, OR = 0.90 (0.82–1.00) and V1 functional Cell Motility pathway, OR = 0.75 (0.62–0.92), whereas V2 bacterial diversity, OR = 1.19 (1.03–1.38) was shown to be predictive of progression to CIN2+. Conclusion This study demonstrates that features of the cervicovaginal microbiome are associated with HR-HPV progression in a prospective longitudinal cohort. The analyses indicated that the association of Gardnerella and progression to CIN2+ may actually be mediated by subsequent elevation of microbial diversity. Identified features of the microbiome associated with HR-HPV progression may be targets for therapeutic manipulation to prevent CIN2+. Trial registration ClinicalTrials.gov NCT00128661.
Article
Objectives Studies investigating the safety of hormone replacement therapy in cervical cancer have predominantly included patients with squamous disease. Pathological studies have identified estrogen receptor positivity in cervical adenocarcinomas. A recent small case-control study suggested a trend towards reduced survival with hormone replacement therapy in cervical adenocarcinomas. Our objective was to determine if hormone replacement therapy use in patients treated for cervical adenocarcinomas is detrimental to survival. Study design A retrospective review of all women under the age of 50 with stage 1B-2B cervical adenocarcinomas diagnosed between 1 November 2000 and 24 September 2019. Women were categorised into three groups: ovaries conserved (OVCON); or iatrogenic menopause with (IM-HRT) or without (IM-NOHRT) hormone replacement therapy. Hormone replacement therapy use was defined on an intention to treat basis. Statistical analysis was performed using Kaplan-Meier and Cox proportional hazards methods. Main outcome measures Overall (OS), disease specific (DSS) and progression free (PFS) survival. Results A total of 58 women (mean age 38.5 ± 6.6) were included in the study of whom 25 (43.1%) had OVCON, 20 (34.4%) had IM-HRT and 13 (22.4%) had IM-NOHRT. No menopause-associated deaths occurred. Although five-year DSS was 73% in IM-NOHRT compared to 95% in IM-HRT and 95% in OVCON, these differences were not statistically significant. Five-year PFS was 68% in IM-NOHRT compared to 90% in IM-HRT and 81% in OVCON but again, these differences were not statistically significant. Conclusion In this small study, hormone replacement therapy does not appear to be detrimental to survival in cervical adenocarcinomas. There is a trend towards improved survival with hormone replacement therapy. Larger studies are required to substantiate these findings.
Chapter
This chapter focuses on various modern birth control methods, including combined oral contraceptives, progestogen-only pills, progestogen-only injectables, progestogen-only implants, intrauterine devices, barrier contraceptives, and emergency contraceptive pills. Each contraceptive method is covered in detail, including mechanism of action, effectiveness, health benefits, advantages, disadvantages, risks, and side-effects.
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Pharmacogenetic study of TP53 gene polymorphisms has not been conducted extensively in cervical cancer. The aim of this study was to assesses the TP53 codon 72 and codon 47 polymorphisms and their relation to cervical cancer risk in Bangladeshi women. 134 cervical cancer patients and 102 age matched healthy controls were included from two institutions in Bangladesh. Polymerase chain reaction-restriction fragment length polymorphism (PCR–RFLP) method was used for genotyping two TP53 single nucleotide polymorphisms (codon 72 and codon 47) in patients and controls. The results indicate that the TP53 Arg/Pro heterozygosity (adjusted OR 2.32, 95% CI 1.28–4.34, p = 0.01), Pro/Pro mutant homozygosity (adjusted OR 4.15, 95% CI 1.75–9.86, p = 0.001), along with the combined genotype (Arg/Pro + Pro/Pro) (adjusted OR 2.83, 95% CI 1.61–4.97, p < 0.001) significantly increases the risk of cervical cancer. Moreover, the cervical cancer patients with a first-degree relative cancer patient possesses 4.45 folds more risk (p = 0.019) of carrying a proline allele in codon 72 of the TP53 gene compared to those patients who do not have any first-degree relative with cancer. Finally, polymorphism in the codon 47 of the TP53 gene did not significantly increase the risk of cervical cancer in Bangladeshi women. To conclude, this is the first study to identify that polymorphism in the TP53 codon 72 significantly increases the risk of cervical cancer in a female population in Bangladesh.
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Purpose of the study . To assess the chances of development of squamous intraepithelial cervical lesions of high degree (H‑SIL) in patients infected with human papillomavirus (HPV). Patients and methods . 75 HPV positive patients. The main group — with a histological diagnosis of H‑SIL (n=50), the control group — with a histological diagnosis without H‑SIL (n=25). Liquid-based cytology, colposcopy, cervical excision; HPV test, diagnosis of sexually transmitted infections — PCR in real time; a comprehensive bacteriological study. Assessment tool interconnections — odds ratio, categorical data analysis — statistical packages STATISTICA 6.0 and SPSS 22 "Statistical Package for the Social Sciences". Results . In the age group up to 30 years, the chances of H‑SIL development are 26 times higher, 30–40 years — 38 times higher compared to patients over 50 years (p<0.05). With a menstrual cycle of more than 35 days, the chances of H‑SIL development are 71 times greater than in patients with a normal menstrual cycle (p<0.05).Comparison of the chances of the presence of abnormal colposcopic patterns — the presence of significant lesions related to the II degree of colposcopic changes increases the chances of H‑SIL 8.4 times compared to the normal colposcopic pattern. The chances of development of H‑SIL in patients with colposcopy results of minor lesions (I degree), do not differ from those who have a normal colposcopic picture (p>0.05). The presence of chronic inflammatory diseases of the pelvic organs. Earlier treatment of cervical diseases by destruction reduces the risk of H‑SIL 0.08 times. The presence of chronic diseases of the pelvic organs increases the risk of H‑SIL 24 times (p<0.05). Conclusion . The group at greatest risk of having H‑SIL -women 30–40 years, whose menstrual cycle is more than 35 days, with significant lesions according to the results of colposcopic examination, chronic diseases of the pelvic organs, which had not previously been carried out destruction of the cervix.
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Perimenopause represents a transition period of a woman’s life during which physiological, affective, psychological, and social changes mark progression from a woman’s fertile life to menopause, with wide sexual hormones fluctuations until the onset of hypergonadotropic hypogonadic amenorrhea. Contraception during menopause should not only avoid unwanted pregnancies, but also improve quality of life and prevent wide range of condition affecting this population. Hormonal contraceptives confer many noncontraceptive benefits for women approaching menopause: treatment of abnormal uterine bleeding, relief from vasomotor symptoms, endometrial protection in women using estrogen therapy, musculoskeletal protection, and mood disorders protection. The main point remains selecting the most adequate contraceptive option for each woman, considering her risk factor, comorbidities, and keeping in mind the possibility of continuing contraception until reaching menopause and even further, creating a bridge between perimenopause and menopause hormonal therapy. Correct perimenopause management should rely on individualized medical therapy and multidisciplinary approach considering lifestyle and food habits as part of general good health of a woman.
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Background Factors that lead human papillomavirus (HPV) infections to persist and progress to cancer are not fully understood, especially among vaccinated women. We evaluated co-factors for acquisition, persistence and progression of non-HPV16/18 infections in a cohort of HPV-vaccinated women. Methods We analyzed 2,153 18-25-year-old women randomized to the HPV-vaccine arm of CVT. Women were HPV-DNA-negative for all types at baseline and followed for ~11 years. Acquisition was a type-specific cervical infection not present/detected at the previously scheduled visit. Persistence was a type-specific incident infection that persisted for ≥1-year with no intervening negatives. Progression of persistent incident infections to CIN2+ was based on histological findings by expert pathologists. GEE methods were used to account for correlated observations. Time-dependent factors evaluated were age, sexual behavior, marital status, hormonal-related factors, number of full-term pregnancies (FTP), smoking behavior, and baseline-BMI. Results 1,777 incident oncogenic non-HPV16/18 infections were detected in 12,292 visits (average 0.14 infections per visit). Age and sexual behavior-related variables were associated with oncogenic non-HPV16/18 acquisition. 26% of incident infections persisted for ≥1-year. None of the factors evaluated were statistically associated with persistence of oncogenic non-HPV16/18 infections. Risk of progression to CIN2+ increased with increasing age (p-trend=0.001), injectable contraceptives use [relative risk 2.61 (95%CI 1.19–5.73) ever vs. never] and increasing FTP (p-trend=0.034). Conclusion In a cohort of HPV16/18-vaccinated women, age and sexual behavior variables are associated with acquisition of oncogenic non-HPV16/18 infections, no notable factors are associated with persistence of acquired oncogenic non-HPV16/18 infections, and age, parity and hormonally-related exposures are associated with progression to CIN2+.
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Human Papillomavirus (HPV) and other germane parameters are considered the leading cause of cervical cancer in women in this study. Our aim is to create awareness about HPV and cervical cancer among both males and females in Nigeria. We developed a risk-score (HAT-Human Papillomavirus Assessment Test) which was used to determine the risk factor(s) with the highest/lowest risk factors for HPV associated infections in both men and women, and cervical cancer progression in women.
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The purpose of this review is to describe the existing literature regarding the relationship between the vaginal microbiome, human papillomavirus persistence, and cervical cancer risk, as well as to discuss factors that mediate these relationships. Data suggest that alterations in the vaginal microbiome affect the risk of human papillomavirus infection and persistence, which has downstream effects on cervical dysplasia and cancer risk. The homeostatic Lactobillus species L. crispatus, L. gasseri, L. jensenii act to promote a healthy vaginal environment, while L. iners and pathogens causing bacterial vaginosis are associated with increased inflammation, human papillomavirus infection, cervical dysplasia, and potentially cancer. There are, however, still several large gaps in the literature, particularly related to the modifiable and non-modifiable factors that affect the vaginal microbiome and ensuing risk of pre-cancerous and cancerous lesions. Evidence currently suggests that endogenous and exogenous hormones, tobacco products, and sexual practices influence vaginal microbiome composition, but the nuances of these relationships and how changes in these factors affect dysplasia risk are yet to be delineated. Other studies examining how diet, exercise, race, socioeconomic status, and genetic factors influence the vaginal microbiome are difficult to interpret in the setting of multiple confounders. Future studies should focus on how changes in these modulatory factors might promote a healthy vaginal microbiome to prevent or treat dysplasia in the lower female genital tract.
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Objective: The US screening and management guidelines for cervical cancer are based on the absolute risk of precancer estimated from large clinical cohorts and trials. Given the widespread transition toward screening with human papillomavirus (HPV) testing, it is important to assess which additional factors to include in clinical risk assessment to optimize management of HPV-infected women. Materials and methods: We analyzed data from HPV-infected women, ages 30-65 years, in the National Cancer Institute-Kaiser Permanente Northern California Persistence and Progression study. We estimated the influence of HPV risk group, cytology result, and selected cofactors on immediate risk of cervical intraepithelial neoplasia grade 3 or higher (CIN 3+) among 16,094 HPV-positive women. Cofactors considered included, age, race/ethnicity, income, smoking, and hormonal contraceptive use. Results: Human papillomavirus risk group and cytology test result were strongly correlated with CIN 3+ risk. After considering cytology and HPV risk group, other cofactors (age, race/ethnicity, income, smoking, and hormonal contraceptive use) had minimal impact on CIN 3+ risk and did not change recommended management based on accepted risk thresholds. We had insufficient data to assess the impact of long-duration heavy smoking, parity, history of sexually transmitted infection, or immunosuppression. Conclusions: In our study at the Kaiser Permanente Northern California, the risk of CIN 3+ was determined mainly by HPV risk group and cytology results, with other cofactors having limited impact in adjusted analyses. This supports the use of HPV and cytology results in risk-based management guidelines.
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Background: Cervical Carcinoma is considered the commonest cancer of the female reproductive system, and it has been identified as a chief public health problem all over the world. In Saudi Arabia, it is responsible about 7% of all recently diagnosed females' carcinomas and it is the 6 th leading cause of cancer deaths among Saudi females. Though cervical cancer is a significant health problem, it's cause is still to be vague. Aim: This study intends to identify the predictors of cervical cancer screening based on the health belief model among Saudi females at maternal and child hospital, Najran. Setting: This study has been conducted in maternal and child hospital (MCH) outpatient clinics. MCH is the largest and only specialized hospital in the Najran region, Kingdom of Saudi Arabia. Research Design: Descriptive correlational research design. Subject A convenience sample of all Saudi females who visited the MCH outpatient department between June till the end of December 2019. Inclusion criteria were Saudi married women aged 20-65 years of age. Tools: Interviewing schedule includes four main parts was used for data collection. The four parts are socio-demographic data logic , obstetric and gyneco , knowledge about cervical cancer, and health belief model history Current study results shows that only 0.7% of the study participants had Results:. scale a history of taking the HPV vaccine. Besides, the total health belief score is moderate edge 68.5% of them. In addition, 71% of the study participant have total fair knowl among regarding cervical cancer. A statistically significant relationship is observed between p women's total HBM scores and their age. Another statistically significant relationshi ical cancer between women's knowledge and their perceived suability and barriers to cerv Although most of the study participants Conclusions and Recommendation: is found. are University educated, they have a moderate health belief and good knowledge d be ding cervical cancer. Accordingly, an intensive educational intervention shoul regar directed to all Saudi females in all settings to increase their health belief and knowledge regarding cervical cancer.
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Extracting useful information from structured and unstructured biological data is crucial in the health industry. Some examples include medical practitioner’s need to identify breast cancer patient in the early stage, estimate survival time of a heart disease patient, or recognize uncommon disease characteristics which suddenly appear. Currently there is an explosion in biological data available in the data bases. But information extraction and true open access to data are require time to resolve issues such as ethical clearance. The emergence of novel IT technologies allows health practitioners to facilitate the comprehensive analyses of medical images, genomes, transcriptomes, and proteomes in health and disease. The information that is extracted from such technologies may soon exert a dramatic change in the pace of medical research and impact considerably on the care of patients. The current research will review the existing technologies being used in heart and cancer research. Finally this research will provide some possible solutions to overcome the limitations of existing technologies. In summary the primary objective of this research is to investigate how existing modern machine learning techniques (with their strength and limitations) are being used in the indent of heartbeat related disease and the early detection of cancer in patients. After an extensive literature review these are the objectives chosen: to develop a new approach to find the association between diseases such as high blood pressure, stroke and heartbeat, to propose an improved feature selection method to analyze huge images and microarray databases for machine learning algorithms in cancer research, to find an automatic distance function selection method for clustering tasks, to discover the most significant risk factors for specific cancers, and to determine the preventive factors for specific cancers that are aligned with the most significant risk factors. Therefore we propose a research plan to attain these objectives within this chapter. The possible solutions of the above objectives are: new heartbeat identification techniques show promising association with the heartbeat patterns and diseases, sensitivity based feature selection methods will be applied to early cancer patient classification, meta learning approaches will be adopted in clustering algorithms to select an automatic distance function, and Apriori algorithm will be applied to discover the significant risks and preventive factors for specific cancers. We expect this research will add significant contributions to the medical professional to enable more accurate diagnosis and better patient care. It will also contribute in other area such as biomedical modeling, medical image analysis and early diseases warning.
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Gynecological neoplasms pose a serious threat to women’s health. It is estimated that in 2020, there were nearly 1.3 million new cases worldwide, from which almost 50% ended in death. The most commonly diagnosed are cervical and endometrial cancers; when it comes to infertility, it affects ~48.5 million couples worldwide and the number is continually rising. Ageing of the population, environmental factors such as dietary habits, environmental pollutants and increasing prevalence of risk factors may affect the reproductive potential in women. Therefore, in order to identify potential risk factors for these issues, attention has been drawn to trace elements. Trace mineral imbalances can be caused by a variety of causes, starting with hereditary diseases, finishing with an incorrect diet or exposure to polluted air or water. In this review, we aimed to summarize the current knowledge regarding trace elements imbalances in the case of gynecologic cancers as well as female fertility and during pregnancy.
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Variable importance, interaction measures, and partial dependence plots are important summaries in the interpretation of statistical and machine learning models. In this paper we describe new visualization techniques for exploring these model summaries. We construct heatmap and graph-based displays showing variable importance and interaction jointly, which are carefully designed to highlight important aspects of the fit. We describe a new matrix-type layout showing all single and bivariate partial dependence plots, and an alternative layout based on graph Eulerians focusing on key subsets. Our new visualizations are model-agnostic and are applicable to regression and classification supervised learning settings. They enhance interpretation even in situations where the number of variables is large. Our R package vivid (variable importance and variable interaction displays) provides an implementation.
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Die Präventivmedizin hat übergreifende gemeinsame Ziele (Verhinderung von Krankheiten, Verhinderung des Fortschreitens und der Ausbreitung von Krankheiten, Minderung von Folgeschäden), die für beide Geschlechter gelten. Im Hinblick auf die Alterungsprävention gibt es neben den Gemeinsamkeiten für Frauen spezifische Aspekte und Strategien basierend auf 2 Konzepten: Sexuelle und Reproduktive Gesundheit und Rechte für Frauen auf der einen Seite und den Life Course Approach, bei dem deutlich wird, dass Alterungsprävention ein lebenlanger Prozess ist
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A case-control study of 293 patients with in situ cervical cancer and 801 community controls was conducted between 1982 and 1984 in five geographic areas in the United States. Relative risk (RR) was elevated among women reporting multiple sexual partners (RR for greater than or equal to 5 partners = 5.0), a history of an abnormal Papanicolaou smear (RR = 5.0), interval since last Papanicolaou smear (RR for greater than or equal to 10-year interval versus 0- to 2-year interval = 4.1), use of oral contraceptives (RR for greater than or equal to 10 years use = 1.4), a history of nonspecific genital infection (RR = 2.6), and smoking (RR for current smokers = 1.9). Risk was low among diaphragm users (RR for greater than 2 years use = 0.5). Neither age at first coitus nor number of births was predictive of risk of in situ disease. Comparisons between this analysis and risk factors previously identified for invasive cervical cancer in this same study indicate that the risk factors were quite similar.
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Oberie M W (Division of Reproductive Health, Centers for Disease Control, Atlanta GA 30333, USA), Rosero-Bixby L, Irwin K L, Fortney J A, Lee N C, Whatley A S, Bonhomme M G. Cervical cancer risk and use of depot-medroxyprogesterone acetate in Costa Rica. International Journal of Epidemiology 1988, 17: 718–723. The relationship between cervical cancer and the use of depot-medroxyprogesterone acetate (DMPA) was examined in a nationwide case-control study in Costa Rica. Cases were women ages 25–58 years of age with invasive squamous cell cancer (N=149) or carcinoma in situ (CIS, N=415) reported by the National Tumor Registry during 1982–84. Controls (N=764) were randomly selected during a nationwide household survey. Using logistic regression, we adjusted for known risk factors for cervical cancer. DMPA use was associated with a risk of CIS of 1.1 (95% confidence interval 0.6–1.8) and a risk of invasive cancer of 1.4 (95% confidence interval 0.6–3.1). The slightly elevated risks observed may be the result of chance or a detection bias. One limitation of this study is that few women had used DMPA for longer than two years.
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To examine the relationship between cervical cancer and oral contraceptive (OC) use, we analyzed data from a population-based, case-control study in Costa Rica. Women aged 25 to 58 years in whom cervical cancer was diagnosed and reported to the National Tumor Registry were examined as two separate case groups: invasive cervical cancer and carcinoma in situ (CIS). Controls were women aged 25 to 58 years identified through a national survey. Women who had used OCs had no increased risk of invasive cervical cancer compared with women who had never used OCs (relative risk, 0.8; 95% confidence interval, 0.5 to 1.3). Women who had used OCs had an increased risk of CIS compared with those who had never used OCs (relative risk, 1.6; 95% confidence interval, 1.2 to 2.2). However, further analyses indicated that this increased risk was confined to those who had recently used OCs. Also, the risk of CIS was not elevated in subgroups in which a history of cervical smears was not strongly linked to OC use. The elevated risk of CIS among OC users may therefore reflect a bias caused by enhanced detection of disease rather than a causal association. (JAMA 1988;259:59-64)
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A case-control study of 525 histologically confirmed cases of cervical intraepithelial neoplasia grade III and 512 controls was done in Spain and Colombia to assess the role of various risk factors taking into account the effect of human papillomavirus (HPV). The presence of HPV DNA, assessed by a polymerase chain reaction-based method, was the strongest risk factor identified. In Spain the adjusted odds ratio (OR) and 95% confidence interval (CI) (numbers in parentheses) were 56.9 (24.8-130.6) and, in Colombia, were 15.5 (8.2-29.4). In addition to HPV, the multivariate analysis revealed independent effects of early age at first intercourse (in Spain ORa, 4.3; 95% CI, 2.0-9.3 for ages < 17 versus 20+ years and in Colombia ORa, 9.0; 95% CI, 2.6-30.9 for ages < 14 versus 20+ years), and antibodies to Chlamydia trachomatis (in Spain ORa, 2.3; 95% CI, 1.1-4.5; and in Colombia ORa, 1.7; 95% CI, 1.1-2.7). High parity showed a significant effect only in Colombia (ORa, 2.0; 95% CI, 1.0-5.0 for > or = 6 versus 1) while number of partners of the woman and specially of her husband showed a strong effect in Spain only (ORa, 6.9; 95% CI, 3.1-15.3 for partners of the husband > or = 21 versus 1-5). Smoking and use of oral contraceptives did not show significant or consistent associations. Among HPV-DNA positive women early age at first intercourse and high parity increased the risk of cervical intraepithelial neoplasia III but the effect was statistically significant only for the former.(ABSTRACT TRUNCATED AT 250 WORDS)
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A case-control study of 525 cases of cervical intraepithelial neoplasia grade III (CIN III) and 512 controls was conducted in Spain and Colombia between 1985 and 1988 to assess the role of human papillomavirus (HPV) in the etiology of CIN III. HPV DNA in cytological scrapes from the cervix was assessed by Virapap and by polymerase chain reaction (PCR) based on the L1 consensus primers. A subsample of 268 specimens was also tested for HPV DNA using Southern hybridization. In Spain, the PCR-based prevalences of HPV DNA were 70.7% among cases and 4.7% among controls. Odds ratio (OR) and 95% confidence interval (numbers in parentheses) for HPV DNA were 56.9 (24.8-130.6). In Columbia HPV DNA was detected by PCR in 63.2% of the cases and in 10.5% of the controls. The OR was 15.5 (8.2-29.4). The estimated fractions of CIN III attributable to HPV were 72.4% in Spain and 60.3% in Colombia. HPV 16 was the predominant viral type and showed the strongest association with CIN III; in Spain the OR was 295.5 (44.8-1946.4) and in Colombia the OR was 27.1 (10.6-69.5). HPV DNA of unknown type was frequent in HPV-positive cases (18.3% in Spain and 38.0% in Colombia) and controls (66.7% in Spain and 47.4% in Colombia). The comparison of results from Virapap and PCR indicated that PCR is the method of choice for epidemiological studies. These data strongly support the hypothesis of the viral origin of CIN III, the common etiology of CIN III and invasive cervical cancer, and the causal nature of the association between HPV and CIN III.
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A hospital-based case-control study was undertaken to examine the role of human papillomavirus (HPV) in the development of invasive cervical cancer in Brazil. The study included 199 histologically confirmed incident cases and 225 age-frequency-matched controls selected from a wide range of diagnostic categories. A polymerase chain reaction technique was used to detect HPV DNA in cervical specimens collected with spatula and brush. HPV DNA was detected in 84% of the cases compared with 17% of controls. Grouping HPV types 16, 18, 31 and 33, 66% of the cases were positive compared with only 6% of the controls. In addition to HPV, number of sexual partners, early age at first intercourse, parity and duration of oral contraceptive use were significantly associated with an increased risk of cervical cancer. A history of previous Papanicolaou smears was significantly associated with a decreased risk. After adjustment, only presence of HPV DNA, parity and history of previous smears remained as independent risk factors. The adjusted odds ratios of cervical cancer associated with HPV 16, 18, 31, and 33 was 69.7 (95% confidence interval 28.7-169.6) and with unidentified types was 12.0 (5.1-28.5). The very high risks found in this study further implicate this virus in the aetiology of cervical cancer.
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It has now been established that infection with human papillomavirus (HPV) is necessary for the development of most cervical cancers. HPV is not sufficient for the development of cancer. Other exposures or host factors are necessary for cancer to occur. As part of an ongoing, population-based case-control study of invasive cervical cancer, we investigated the role of cigarette smoking, oral contraceptive (OC) use, and herpes simplex virus type 2 (HSV-2) as potential cofactors with HPV in the development of cervical cancer. Residents of three counties in western Washington State who were diagnosed with invasive squamous cell cervical cancer (n = 314) from January 1986 through December 1992 were interviewed about their sexual, reproductive, contraceptive, and cigarette smoking histories. Similar information was obtained from control women identified through random digit dialing (n = 672). The sera from 206 cases and 522 controls were tested for both HPV 16 capsid antibodies and HSV-2 antibodies. PCR was used to test paraffin-embedded tumor tissues for the presence of HPV DNA types 6, 16, 18, 31, 33, 35, and 39. Women with cervical cancer were more likely to be current smokers at diagnosis than population controls [relative risk (RR), 2.5; 95% confidence interval (CI), 1.8-3.4]. The risk associated with smoking was present to a similar extent among women positive and negative for HPV as measured by HPV 16 capsid antibodies and HPV DNA in the tumor tissue (cases). OC use was only important if first use was at an early age, particularly ages < or = 17 years (RR, 2.3; 95% CI, 1.4-3.8). There was only a slight risk for cervical cancer associated with antibodies to HSV-2 (RR, 1.2; 95% CI, 0.9-1.7). However, when we stratified by markers of HPV exposure, we found a significant increase in risk associated with HSV-2 among women negative for HPV 16 antibodies (RR, 2.0; 95% CI, 1.3-3.0), which was strengthened when we confined our analysis to cases whose tumors were HPV DNA negative (RR, 3.6; 95% CI, 1.6-8.0). There was no indication that cigarette smoking, OC use, or HSV-2 infection influence the ability of HPV infection to cause invasive cervical cancer. OC use may only be important in the etiology of invasive squamous cell cervical tumors if the use occurs at a critical time in the development of a woman's reproductive tract, at ages < or = 17 years. The majority of risk associated with HSV-2 was confined to HPV-negative tumors, indicating a possible separate pathway to disease that may account for 5-10% of invasive cervical cancers.
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Human papillomaviruses (HPV) types 16 and 18 are clearly involved in the etiology of cervical cancer, but the evidence for the carcinogenicity of other HPV types is limited. Cofactors involved in the progression from infection with HPV to high-grade precursors and cancer have not been clearly defined by the results of previous studies. We conducted a hospital-based, case-control study of invasive cervical cancer to investigate risk in relation to HPV infection and its epidemiologic cofactors in Hat-Yai, Thailand. A total of 338 patients with squamous cell carcinoma, 39 patients with adenocarcinoma/adenosquamous carcinoma, and 261 control subjects were included in the study and were interviewed to obtain information with regard to cervical cancer risk factors. HPV DNA presence in cervical exfoliated cells or frozen biopsy specimens was determined by a polymerase chain reaction assay. HPV DNA was detected in 95% of patients with squamous cell carcinoma, 90% of those with adenocarcinoma/adenosquamous carcinoma, and 16% of control subjects. For patients with squamous cell carcinoma, the most common types of HPV found were type 16 (60% of the positives), type 18 (18%), type 58 (3%), type 52 (3%), and type 31 (2%). For patients with adenocarcinoma/adenosquamous carcinoma, the most common HPV types found were type 18 (60% of the positives), type 16 (37%), and type 45 (3%). The risk factors that remained associated with risk of both histologic types after adjustment for HPV and their mutual confounding effects were limited education, increasing number of sexual partners, history of venereal diseases, and interval since last Pap smear (i.e., cytologic) test. Among patients with squamous cell carcinoma, some association with smoking was also observed. New preventive strategies for cervical cancer will require the consideration of multiple HPV types.
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Among the numerous human papillomavirus (HPV) types, only types 16 and 18 have been formally classified as human carcinogens. To evaluate the associations of 33 HPV types and other risk factors with squamous cell carcinoma and adenocarcinoma of the cervix, we performed a hospital-based, case-control study in the Philippines. The study included 356 case subjects who had histologically confirmed cervical cancer (323 incident cases of squamous cell carcinoma and 33 incident cases of adenocarcinoma/adenosquamous carcinoma) and 381 control subjects. Information on risk factors was obtained by personal interview. HPV DNA was detected in exfoliated cervical cells and biopsy specimens by use of a polymerase chain reaction assay. HPV DNA was detected in 93.8% of case subjects with squamous cell carcinoma and in 90.9% of case subjects with adenocarcinoma/adenosquamous carcinoma compared with 9.2% of control subjects, giving age-adjusted odds ratios of 156 (95% confidence interval [CI] = 87-280) for squamous cell carcinoma and 111 (95% CI = 31-392) for adenocarcinoma/adenosquamous carcinoma. Fifteen different HPV types were detected in squamous cell carcinoma, and six different HPV types were detected in adenocarcinoma/adenosquamous carcinoma. Among HPV types other than types 16 and 18, the associations of HPV with risk of squamous cell carcinoma were strongest for HPV45. In addition to HPV, high parity, low socioeconomic status, and smoking were also associated with both types of cervical cancer. As has been shown for squamous cell carcinoma, HPV is the central cause of adenocarcinoma/adenosquamous carcinoma of the uterine cervix. The observed associations of less prevalent HPV types with cervical cancer have important implications for cervical cancer prevention strategies.
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HPV types 16 and 18 have been categorized as human carcinogens based on their strong associations with cervical cancer in previous case‐control studies. Recent IARC studies in the Philippines, Thailand and Morocco show strong associations between invasive cervical cancer and less common HPV types, including HPV 31, 33, 45, 51, 52 and 58. We present results of a further IARC case‐control study conducted in Asunción, Paraguay, to examine the association between specific HPV types and invasive cervical cancer as well as risk factors other than HPV. One‐hundred thirteen incident histologically confirmed invasive cervical cancer cases and 91 age‐matched hospital controls were recruited. A standardized questionnaire was administered to investigate known and suspected risk factors for cervical cancer. For HPV status determination, cervical biopsy specimens from case subjects and exfoliated cervical cells from control subjects were obtained. HPV DNA was ascertained using a GP5+/6+ PCR‐based assay capable of detecting more than 33 HPV types. Overall HPV prevalence was 97% in the cervical cancer cases and 20% in the control subjects. As a single infection, HPV 16 was the predominant type with a prevalence of 48% among case subjects and 5.5% among control subjects. Significant associations with the risk of cervical cancer were detected as follows: any HPV type (OR = 114; 95% CI: 36–361); HPV 16 (OR = 910); HPV 18 (infinite OR); HPV 31 (OR = 110); HPV 33 (OR = 261); HPV 45 (OR = 129); and HPV 58 (OR = 36). In the multivariate model, risk factors other than HPV significantly associated with cervical cancer risk were a higher number of lifetime sexual partners, lower educational status and never having had a Pap smear. Strong associations were found between invasive cervical cancer and specific HPV types 16, 18, 31, 33, 45 and 58. Int. J. Cancer 85:486–491, 2000. © 2000 Wiley‐Liss, Inc.
Article
A recent report that 93 per cent of invasive cervical cancers worldwide contain human papillomavirus (HPV) may be an underestimate, due to sample inadequacy or integration events affecting the HPV L1 gene, which is the target of the polymerase chain reaction (PCR)‐based test which was used. The formerly HPV‐negative cases from this study have therefore been reanalysed for HPV serum antibodies and HPV DNA. Serology for HPV 16 VLPs, E6, and E7 antibodies was performed on 49 of the 66 cases which were HPV‐negative and a sample of 48 of the 866 cases which were HPV‐positive in the original study. Moreover, 55 of the 66 formerly HPV‐negative biopsies were also reanalysed by a sandwich procedure in which the outer sections in a series of sections are used for histological review, while the inner sections are assayed by three different HPV PCR assays targeting different open reading frames (ORFs). No significant difference was found in serology for HPV 16 proteins between the cases that were originally HPV PCR‐negative and ‐positive. Type‐specific E7 PCR for 14 high‐risk HPV types detected HPV DNA in 38 (69 per cent) of the 55 originally HPV‐negative and amplifiable specimens. The HPV types detected were 16, 18, 31, 33, 39, 45, 52, and 58. Two (4 per cent) additional cases were only HPV DNA‐positive by E1 and/or L1 consensus PCR. Histological analysis of the 55 specimens revealed that 21 were qualitatively inadequate. Only two of the 34 adequate samples were HPV‐negative on all PCR tests, as against 13 of the 21 that were inadequate ( p < 0·001). Combining the data from this and the previous study and excluding inadequate specimens, the worldwide HPV prevalence in cervical carcinomas is 99·7 per cent. The presence of HPV in virtually all cervical cancers implies the highest worldwide attributable fraction so far reported for a specific cause of any major human cancer. The extreme rarity of HPV‐negative cancers reinforces the rationale for HPV testing in addition to, or even instead of, cervical cytology in routine cervical screening. Copyright © 1999 John Wiley & Sons, Ltd.
Article
A case-control study among white women in Los Angeles County was conducted to investigate etiologic factors that might explain the high rates of invasive cervical cancer among Latinas. Two hundred patients with invasive squamous cell carcinoma of the uterine cervix and matched (age, sex, preferred language, and neighborhood) controls were interviewed, 98 pairs in English and 102 pairs in Spanish. Seven factors were found to contribute independently and significantly (P<.01) to risk, each after adjustment for the other six: years since last Pap smear, years of education (protective), frequency-years of douching, pack-years of smoking, years of barrier contraceptive use (protective), number of sexual partners before age 20, and recognized episodes of genital warts. An eighth variable, interval in years between menarche and first intercourse, was the second variable to enter the stepwise logistic regression analysis but lost its statistical significance when sexual partners before age 20 entered the model. Together, these eight variables accounted for almost 99% of the risk. There were no significant interactions between any of these variables and age, language of interview, or birth in a Latin country. There was no increased risk associated with use of oral contraceptives, either before or after adjustment for the other significant factors. Compared to English-speaking controls, Spanish-speaking controls smoked less, douched less, had fewer sexual partners before 20, and had essentially the same average interval between menarche and first intercourse and the same average number of episodes of genital warts; however, they had had a longer interval since their last Pap smear, fewer years of barrier contraceptive use, and fewer years of education. Education, presumably a correlate of an inadequately measured etiologic risk factor (possibly papillomavirus infection), was responsible for the greatest difference in risk between the Spanish- and English-speaking cases.
Article
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To determine whether the long-acting progestational contraceptive, depot-medroxyprogesterone acetate (DMPA), alters risk of cervical cancer, a hospital-based case-control study was conducted in two hospitals in Bangkok, Thailand, and in one hospital each in Chiang Mai, Thailand, Mexico City, Mexico, and Nairobi, Kenya. Information on prior use of DMPA, screening for cervical cancer, and the suspected risk factors for this disease was ascertained from interviews of 2,009 women with invasive squamous cell cervical cancer and 9,583 controls. For selected subsets of these women, a smoking history was also elicited, blood specimens were collected for measurement of antibodies against herpes simplex and cytomegaloviruses, and information on sexual behavior was obtained from interviews with their husbands. The relative risk (and 95% confidence interval) of invasive squamous cell cervical carcinoma in women who ever used DMPA was estimated to be 1.11(0.96, 1.29). No trends in risk with duration of use or times since initial or most recent exposure were observed. These results provide reassurance that prolonged use of DMPA does not enhance risk of invasive squamous cell cervical carcinomas, even after a potential latent period of over a decade.
Article
Data from a hospital-based case-control study collected in 11 participating centers in 9 countries were analyzed to determine whether use of combined oral contraceptives alters risk of invasive squamous-cell cervical cancer. Information on prior use of oral contraceptives, screening for cervical cancer, and suspected risk factors for this disease were ascertained from interviews of 2361 cases and 13,644 controls. A history of smoking and anal and genital warts was obtained, and blood specimens were collected for measurement of antibodies against herpes simplex and cytomegalo viruses, from selected sub-sets of these women, as was a sexual history from interviews of husbands. The relative risk of invasive squamous-cell cervical carcinoma was estimated to be 1.31, with a 95% confidence interval that excluded one, in women who ever used combined oral contraceptives. Risk of this disease increased significantly with duration of use after 4 to 5 years from first exposure, and declined with the passage of time after cessation of use to that of non-users in about 8 years. No sources of bias or confounding were identified that offered plausible explanations for these findings. The strength of these results, and their consistency with those from other studies, suggest that a causal relationship may exist between use of combined oral contraceptives and squamous-cell cervical carcinoma. Women who have used these products for 4 or more years, and who most recently used them within the past 8 years, should receive high priority for cervical cytologic screening.
Article
Of 47 000 women followed since 1968, those who had used oral contraceptives (ever-users) had a significantly higher incidence rate of cervical cancer than never-users. After standardisation of rates by age, parity, smoking, social class, number of previously normal cervical smears, and history of sexually transmitted disease, the excess was 41 per 100 000 woman-years for carcinoma-in-situ and 8 per 100 000 woman-years for invasive cervical cancer. Incidence increased with increasing duration of use: the standardised incidence rate for cervical cancer in women who had taken the pill for more than 10 years was four times that in never-users. Ever-users had a lower incidence of other uterine cancers (deficit 5 per 100 000 woman-years); a lower incidence of ovarian cancer was also found (deficit 4 per 100 000), but was not statistically significant. Overall, ever-users had an excess incidence for genital tract cancers of 37 per 100 000 woman-years. This excess was mainly from carcinoma-in-situ of the cervix; the excess incidence of invasive cervical cancer was offset by the deficits in other uterine and ovarian cancers. Standardised mortality rates from genital cancer were similar in ever-users and never-users. Of relevance to clinical practice is the substantially different distribution of primary cancer sites: cervical cancer accounted for 75% of the invasive genital cancers and 74% of deaths from genital cancer in ever-users, but only 31% of the invasive cancers and 30% of deaths in never-users.
Article
Binary response variables special logistical analyses some complications some related approaches more complex responses. Appendices: Theoretical background Choice of explanatory variables in multiple regression Review of computational aspects Further results and exercises.
Article
Data from a hospital-based case-control study collected in 11 participating centers in 9 countries were analyzed to determine whether use of combined oral contraceptives alters risk of invasive squamous-cell cervical cancer. Information on prior use of oral contraceptives, screening for cervical cancer, and suspected risk factors for this disease were ascertained from interviews of 2361 cases and 13,644 controls. A history of smoking and anal and genital warts was obtained, and blood specimens were collected for measurement of antibodies against herpes simplex and cytomegalo viruses, from selected sub-sets of these women, as was a sexual history from interviews of husbands. The relative risk of invasive squamous-cell cervical carcinoma was estimated to be 1.31, with a 95% confidence interval that excluded one, in women who ever used combined oral contraceptives. Risk of this disease increased significantly with duration of use after 4 to 5 years from first exposure, and declined with the passage of time after cessation of use to that of non-users in about 8 years. No sources of bias or confounding were identified that offered plausible explanations for these findings. The strength of these results, and their consistency with those from other studies, suggest that a causal relationship may exist between use of combined oral contraceptives and squamous-cell cervical carcinoma. Women who have used these products for 4 or more years, and who most recently used them within the past 8 years, should receive high priority for cervical cytologic screening.
Article
In a case-control study conducted in Latin America, the relationship of injectable contraceptive (IC) use to risk of in vasive cervical cancer was analyzed while controlling for a variety of other risk factors, including female and spouse sexual behavior and infection with human papillomaviruses (HPV). Thirty-two cases and 82 controls reported ever having used IC. Women reporting use of IC for less than 5 years had an adjusted RR of 0.5 (95% CI = 0.3-0.9), but users for 5 or more years had an RR of 2.4 (95% Cl = 1.0-5.7). The effect of prolonged 1C use was stronger for women reporting first use 10 or more years before interview (adjusted RR = 3.4, 95% Cl = 1.1-24.9) and more than 5 years since last use (adjusted RR = 5.3, 95% Cl = 1.1-10.0). Cervical cancer risk associated with prolonged IC use was particularly high among women who reported never having had a Pap smear or having had one 2 or more years before interview (adjusted RR = 6.3, 95% CI = 2.1-18.7). The reduced cervical cancer risk associated with short-term use of IC may reflect intensive Pap smear screening as the method is initiated. Although hampered by small numbers, these results suggest an adverse effect of prolonged IC use on cervical cancer risk, particularly among women who cease participation in screening programs after terminating usage, and indicate that long-term IC users should be monitored for cervical disease until more conclusive results are available.
Article
Human papillomavirus (HPV) is probably a necessary but definitely not a sufficient cause of cervical carcinoma. However, it remains unclear which factors, in addition to HPV, are important for the development of cervical carcinoma and its precursor lesions. To address this issue, we conducted a case-control study nested in a population-based cohort consisting of women participating in cytological screening in one Swedish county, any time during 1969 through 1995. Detailed information on sexual practice, smoking habits and oral contraceptive (OC) use were collected through telephone interviews with 422 case patients diagnosed with cervical carcinoma in situ and 422 control subjects. All cytological smears were analyzed for presence of HPV16/18 by a polymerase chain reaction (PCR)-based method. Odds ratios (OR) were used as measures of relative risk. After multivariate adjustment, a 2-fold higher risk was observed among current smokers compared with never smokers [OR 1.94; 95% confidence interval (CI 1.32–2.85)], an association apparently confined to women younger than 45 years. Current use of OCs was associated with a 4-fold increased risk overall (OR 3.64; 95% CI 1.91–6.93) with a monotonic increase with increasing duration of use (p for trend < 0.001). The number of sexual partners was significantly, positively associated with risk among HPV 16/18-negative (p for trend < 0.005) but not among HPV 16/18-positive women. Our data confirm the association between smoking and cervical carcinoma in situ, which might be age-dependent. Our results further indicate a relation with OC use and the risk for cervical carcinoma in situ. Int. J. Cancer 81:357–365, 1999. © 1999 Wiley-Liss, Inc.
Article
HPV types 16 and 18 have been categorized as human carcinogens based on their strong associations with cervical cancer in previous case-control studies. Recent IARC studies in the Philippines, Thailand and Morocco show strong associations between invasive cervical cancer and less common HPV types, including HPV 31, 33, 45, 51, 52 and 58. We present results of a further IARC case-control study conducted in Asunción, Paraguay, to examine the association between specific HPV types and invasive cervical cancer as well as risk factors other than HPV. One-hundred thirteen incident histologically confirmed invasive cervical cancer cases and 91 age-matched hospital controls were recruited. A standardized questionnaire was administered to investigate known and suspected risk factors for cervical cancer. For HPV status determination, cervical biopsy specimens from case subjects and exfoliated cervical cells from control subjects were obtained. HPV DNA was ascertained using a GP5+/6+ PCR-based assay capable of detecting more than 33 HPV types. Overall HPV prevalence was 97% in the cervical cancer cases and 20% in the control subjects. As a single infection, HPV 16 was the predominant type with a prevalence of 48% among case subjects and 5.5% among control subjects. Significant associations with the risk of cervical cancer were detected as follows: any HPV type (OR = 114; 95% CI: 36–361); HPV 16 (OR = 910); HPV 18 (infinite OR); HPV 31 (OR = 110); HPV 33 (OR = 261); HPV 45 (OR = 129); and HPV 58 (OR = 36). In the multivariate model, risk factors other than HPV significantly associated with cervical cancer risk were a higher number of lifetime sexual partners, lower educational status and never having had a Pap smear. Strong associations were found between invasive cervical cancer and specific HPV types 16, 18, 31, 33, 45 and 58. Int. J. Cancer 85:486–491, 2000. © 2000 Wiley-Liss, Inc.
Article
Use of oral contraceptives could increase risk of cervical cancer; however the effect of human papillomavirus (HPV), the main cause of cervical cancer, is not usually taken into account. We aimed to assess how use of oral contraceptives affected risk of cervical cancer in women who tested positive for HPV DNA. We pooled data from eight case-control studies of patients with histologically confirmed invasive cervical carcinoma (ICC) and from two studies of patients with carcinoma in situ (ISC). Information about use of oral contraceptives was obtained from personal interviews. Effects were estimated as odds ratios, with logistic-regression models adjusted for possible confounders. 1465 of 1561 (94%) patients with ICC, 211 of 292 (72%) with ISC, and 255 of 1916 (13%) controls were positive for HPV DNA. Compared with never-users, patients who had used oral contraceptives for fewer than 5 years did not have increased risk of cervical cancer (odds ratio 0.73; 95% CI 0.52-1.03). The odds ratio for use of oral contraceptives was 2.82 (95% CI 1.46-5.42) for 5-9 years, and 4.03 (2.09-8.02) for use for 10 years or longer, and these risks did not vary by time since first or last use. Long-term use of oral contraceptives could be a cofactor that increases risk of cervical carcinoma by up to four-fold in women who are positive for cervical HPV DNA. In the absence of worldwide information about HPV status, extra effort should be made to include long-term users of oral contraceptives in cervical screening programmes.
Article
To evaluate the association between human papillomavirus (HPV) and cervical cancer, we performed a population-based case-control study in Colombia and Spain, the former country having an incidence rate of cervical cancer about 8 times higher than the latter. It included 436 cases of histologically confirmed invasive cervical cancer and 387 randomly selected population controls. Information on demographic variables, sexual behaviour and other risk factors was obtained by interview. HPV-DNA was measured in cervical-swab specimens with 3 hybridization assays: ViraPap™, Southern hybridization (SH) and polymerase chain reaction (PCR). The presence of HPV-DNA and detection of types 16, 18, 31, 33 and 35 were strongly associated with cervical cancer in each country regardless of the assay used. For both countries combined the adjusted odds ratios and 95% confidence intervals were: ViraPap OR = 25.9 (10.0–66.7); SH OR = 6.8 (3.4–13.4); and PCR OR = 28.8 (15.7–52.6). HPV-16 was the most common type detected in both cases and controls. Our results indicate that there is a very strong association between HPV 16, 18, 31, 33 and 35 and invasive cervical cancer and that this association is probably causal. © 1992 Wiley-Liss, Inc.
Article
The Collaborative Group on Hormonal Factors in Breast Cancer has brought together and reanalysed the worldwide epidemiological evidence on breast cancer risk and use of hormonal contraceptives. Original data from 54 studies, representing about 90% of the information available on the topic, were collected, checked and analysed centrally. The 54 studies were performed in 26 countries and include a total of 53,297 women with breast cancer and 100,239 women without breast cancer. The studies were varied in their design, setting and timing. Most information came from case-control studies with controls chosen from the general population; most women resided in Europe or North America and most cancers were diagnosed during the 1980s. Overall 41% of the women with breast cancer and 40% of the women without breast cancer had used oral contraceptives at some time; the median age at first use was 26 years, the median duration of use was 3 years, the median year of first use was 1968, the median time since first use was 16 years, and the median time since last use was 9 years. The main findings, summarised elsewhere, are that there is a small increase in the risk of having breast cancer diagnosed in current users of combined oral contraceptives and in women who had stopped use in the past 10 years but that there is no evidence of an increase in the risk more than 10 years after stopping use. In addition, the cancers diagnosed in women who had used oral contraceptives tended to be less advanced clinically than the cancers diagnosed in women who had not used them. Despite the large number of possibilities investigated, few factors appeared to modify the main findings either in recent or in past users. For recent users who began use before age 20 the relative risks are higher than for recent users who began at older ages. For women whose use of oral contraceptives ceased more than 10 years before there was some suggestion of a reduction in breast cancer risk in certain subgroups, with a deficit of tumors that had spread beyond the breast, especially among women who had used preparations containing the highest doses of oestrogen and progestogen. These findings are unexpected and need to be confirmed. Although these data represent most of the epidemiological evidence on the topic to date, there is still insufficient information to comment reliably about the effects of specific types of oestrogen or of progestogen. What evidence there is suggests, however, no major differences in the effects for specific types of oestrogen or of progestogen and that the pattern of risk associated with use of hormonal contraceptives containing progestogens alone may be similar to that observed for preparations containing both oestrogens and progestogens. On the basis of these results, there is little difference between women who have and have not used combined oral contraceptives in terms of the estimated cumulative number of breast cancers diagnosed during the period from starting use up to 20 years after stopping. The cancers diagnosed in women who have used oral contraceptives are, however, less advanced clinically than the cancers diagnosed in never users. Further research is needed to establish whether the associations described here are due to earlier diagnosis of breast cancer in women who have used oral contraceptives, to the biological effects of the hormonal contraceptives or to a combination of both. Little information is as yet available about the effects on breast cancer risk of oral contraceptive use that ceased more than 20 years before and as such data accumulate it will be necessary to re-examine the worldwide evidence.
Article
To assess the hypothesis that oral contraceptives (OCs) increase the risk of cervical adenocarcinomas, we conducted a six-center case-control study of 124 patients with adenocarcinomas, 139 with squamous cell carcinomas, and 307 population controls. Women between the ages of 18 and 69 who were newly diagnosed with cervical adenocarcinomas between 1992 and 1996 were eligible. Healthy female controls and a second case group of incident cervical squamous cell carcinomas were matched to the adenocarcinoma cases. All participants were interviewed regarding OCs, other risk factors for cervical carcinoma, and utilization of cytological screening, and a PCR-based test determined HPV genotype of cervical samples for both case groups and controls. Use of OCs was positively and significantly associated with adenocarcinomas and positively but weakly associated with squamous cell carcinomas. Associations between OCs and invasive adenocarcinomas (n = 91), squamous cell carcinoma in situ (n = 48), and invasive squamous cell carcinomas (n = 91) disappeared after accounting for HPV infection, sexual history, and cytological screening, but a positive association remained between current use of OCs and cervical adenocarcinoma in situ (n = 33). This association persisted after stratification by screening and sexual history and after restriction according to HPV status, but small numbers made it difficult to exclude detection bias, selection bias, or residual confounding by HPV as potential explanations Current OC use was associated with cervical adenocarcinomas in situ, but we saw no other evidence that OCs independently increase the risk of cervical carcinomas.
Article
Background. Although the possible influence of oral contraceptives on risk of cervical carcinoma in situ has been the subject of multiple prior investigations, the results have been inconsistent. Methods. Data from a multinational, collaborative case-control study were analysed to investigate further this possible relationship. To assess potential screening bias, some statistical analyses were restricted to subgroups of cases with and without symptoms at the time of their diagnosis. Results. Relative risk estimates in relation to various features of oral contraceptive use tended to be highest for asymptomatic disease, lowest for disease presenting with vaginal bleeding, and intermediate for disease presenting with other symptoms, suggesting the presence of a screening bias. In women with vaginal bleeding, who are least likely to have been detected by routine screening, no elevated risk of cervical carcinoma in situ was observed in relation to ever having used combined oral contraceptives, but there was an increased risk in users of over 60 months' duration. An increasing trend in risk with duration of use was most pronounced in these women who first used oral contraceptives in the past 5–10 years; and in women who used oral contraceptives for more than 60 months, risk declined with time since last use. Conclusion. These findings could reflect a reversible effect of long-term use of oral contraceptives at an intermediate stage in the carcinogenic process, or a non-causal relationship due to unidentified sources of bias or confounding
Article
Data from a hospital-based case-control study collected between 1979 and 1988 in 10 participating hospitals in eight countries were analyzed to determine whether use of combined oral contraceptives atters the risks of invasive adenocarcinomas and adenosquamous carcinomas of the uterine cervix. Information on prior use of oral contraceptives, suspected risk factors for cervical cancer, and history of cytologic screening was ascertained from interviews with 271 women with adenocarcinomas, 106 with adenosquamous carcinomas, and a large pool of hospitalized controls, from which 2,887 were matched to the cases included in this report. History of smoking and anogenrtal warts and blood specimens for measurement of herpes simplex and cytomegalovirus antibodies were obtained from subsets of these women, as was a sexual history from a subset of their husbands. The epidemiologic features and associations with oral contraceptives were similar for adenocarcinoma and adenosquamous carcinoma. For both types combined, risk increased with duration of oral contraceptive use, was highest in recent and current users, and declined with time since cessation of use. These trends in risk were strongest for cancers that occurred in women under age 35 years, and the association with risk was somewhat stronger for high compared with low progestin potency products. The strength of the observed relation with oral contraceptives was about the same as has been observed for invasive squamous cell cervical carcinomas. Women who have used oral contraceptives should be considered at increased risk of adenomatous cervical carcinomas. Am J Epidemiol 1996; 144: 281–9.
Article
A population-based case-control study of cervical cancer was conducted in Spain and Colombia to assess the relationship between cervical cancer and exposure to human papillomavirus (HPV), selected aspects of sexual and reproductive behaviour, use of oral contraceptives, screening practices and smoking. The study included 436 cases of histologically confirmed squamous-cell carcinoma and 387 age-stratified controls randomly selected from the general population that generated the cases. The presence of HPV DNA in cervical scrapes was assessed by PCR-based methods and was the strongest risk factor (OR = 23.8; 13.4-42.0). Risk estimates for any other factor were only slightly modified after adjusting for HPV status. Among women found positive for HPV DNA, only the use of oral contraceptives was a risk factor for cervical cancer (OR = 6.5; 1.3-31.4 for ever vs. never use). Patients with cervical cancer who were HPV DNA-negative retained most of the established epidemiological features of this disease. This suggests that some instances of HPV infection went undetected or that other sexually transmitted factor(s) contribute to the causation of cervical cancer. Early age at first intercourse (OR = 4.3; 2.1-9.0 for age < 16 vs. 24+) and early age at first birth (OR = 5.0; 1.8-14.2 for age < 16 vs. 24+) were associated with increased risk of cervical cancer; these effects were independent of one another. Low educational level was a risk factor (OR = 2.5; 1.6-3.9). Number of sexual partners was in our study a surrogate for HPV infection. Smoking and parity after age 24 were weakly and inconsistently associated with the risk of cervical cancer. Previous screening (OR = 0.7; 0.5-1.0) and ever having undergone a Caesarean section (OR = 0.4; 0.2-0.8) were protective factors.