[show abstract][hide abstract] ABSTRACT: ABSTRACT The role of nuclear morphometry as a prognostic factor in breast cancer is well documented. The aim of this study was to evaluate this role in breast cancer in Saudi patients and to compare it with the experience in some African and European studies.
Primary tumors from 135 patients were analyzed using an image overlay drawing system (Prodit Morphometry Program), for the following nuclear features: area, perimeter, diameter, and roundness.
The mean nuclear area (NA) was 93 microm(2) (range 45-168 microm(2)). The values of NA were higher in lymph node-positive patients than lymph node-negative patients and in advanced stages than early cancer. NA was significantly larger in patients with high grade tumor (p<0.0001) and in cases with tumor invasion (p<0.01). NA also was significantly larger in recurrent cases (103 microm(2)) than in non-recurrent ones (91 microm(2)). In univariate (Kaplan-Meier) analysis, NA was a significant predictor of disease-free survival (DFS) (log rank p<0.01), but not disease-specific survival (DSS). In multivariate (Cox) survival analysis, NA lost its significance as an independent predictor; response to treatment (p=0.0001) and tumor grade (p=0.030) being the only predictors of DFS. In a similar analysis for DSS, recurrence (p=0.040) and stage (p=0.003) were the only independent predictors.
Nuclear morphometric profiles are helpful in identifying aggressive tumor phenotype (i.e. cases at risk for recurrence). The cut-off (93 mum(2)) of NA might be applied as quantitative criterion for Saudi female breast cancer to separate patients into good and poor prognosis groups. Mean NA of Saudi patients was markedly higher than the reported mean NA in the other studies and these differences might be due to technical variations or genetic bases.
[show abstract][hide abstract] ABSTRACT: Human papillomavirus (HPV) infections are associated with sexual behavior. Changes in the sexual habits of couples and their impact on male genital and oral HPV infections were determined during 7 years of follow-up (FU). At baseline and 7 years FU, urethral, semen/penile, and oral samples were collected from 46 men and cervical and oral samples of their spouses for HPV DNA detection. Demographic data and risk factors of spouses were recorded by questionnaire at both time points and analyzed for concordance. HPV genotyping was done with the Multimetrix® kit. At baseline, 29.5 % of the male genital and 11 % of their oral samples tested positive. Incident genital HPV infection was found in 23 % and oral infection in 10.9 % of men. Genotype-specific persistence was detected in one man (HPV53) in genital samples. Moderate to almost perfect concordance of changes in sexual habits during FU among spouses were found. Changing partners [p = 0.028; odds ratio (OR) = 15; 95 % confidence interval (CI) 1.355-166.054] and marital status (p = 0.001; 95 % CI 0.000-0.002) increased the risk of incident genital HPV infections. The overall outcome of genital HPV disease in men was linked to the frequency of sexual intercourse (p = 0.023; 95 % CI 0.019-0.026) and changes in marital status (p = 0.022; 95 % CI 0.019-0.026), while oral HPV infections were associated with the number of sexual partners (p = 0.047; 95 % CI 0.041-0.052). Taken together, asymptomatic genital HPV infections among the men were common. The risk of incident genital HPV infections increased among men reporting a change of sexual partner during FU, implicating that a stable marital relationship protects against oral and genital HPV infection.
European Journal of Clinical Microbiology 02/2014; · 3.02 Impact Factor
[show abstract][hide abstract] ABSTRACT: Persistent high-risk human papillomavirus (HR-HPV) infection is the key event in the progression of HPV lesions, and more data are urgently needed on asymptomatic oral HPV infections in men. Asymptomatic fathers-to-be (n = 131, mean age 28.9 years) were enrolled in the cohort, sampled by serial oral scrapings at baseline and at 2-month, 6-month, 12-month, 24-month, 36-month, and 7-year follow-up visits to accomplish persistent and cleared HPV infections. HPV genotyping was performed using nested PCR and Multimetrix® assay. Covariates of persistent and cleared oral HPV infections were analysed using generalised estimating equation (GEE) and Poisson regression. Altogether, 17 HPV genotypes were detected in male oral mucosa point prevalence, varying from 15.1 % to 31.1 %. Genotype-specific HPV persistence was detected in 18/129 men the mean persistence time ranging from 6.0 to 30.7 months. History of genital warts decreased (p = 0.0001; OR = 0.41, 95 % CI 0.33-0.51) and smoking increased (p = 0.033, OR = 1.92, 95 % CI 1.05-3.50) the risk of persistent species 7/9 HPV infections. Of the 74 HPV-positive men, 71.6 % cleared their infection actuarial and crude clearance times, varying between 1.4 and 79.6 months. No independent predictors were identified for species 7/9 clearance. At the last follow-up-visit, 50.1 % of the fathers had oral mucosal changes, correlating only with smoking (p = 0.046). To conclude, most of the persisting oral infections in males were caused by HPV16. Smoking increased while previous genital warts decreased oral HR-HPV persistence. No predictors of HR-HPV clearance were disclosed.
European Journal of Clinical Microbiology 09/2013; · 3.02 Impact Factor
[show abstract][hide abstract] ABSTRACT: Despite compelling evidence from the genetic background and clinical studies indicating that cyclooxygenase-2 (COX2) up-regulation is a key step in carcinogenesis of colorectal carcinoma (CRC), controversy regarding its role as a prognostic factor exists. However, all evidence indicates that increased COX2 activity promotes progression of CRC. This study, aimed to evaluate the expression of COX2 in CRC, and correlate it with different patient clinicopathological data, emphasizing on the role of COX2 as a prognostic factor for CRC.
In the present study, archival samples from 145 patients with stage I, II, III, or IV CRC treated during 1981-1990 at the Turku University Hospital (Finland) were used (as microarray blocks) to analyze COX2 expression by immunohistochemistry (IHC).
Higher levels of COX2 expression were associated with higher TNM class (p<0.06), and higher Dukes' stage (p<0.045). In contrast, there was no significant correlation with age, gender, tumor grade or lymph node status. However, univariate survival analysis of metastases showed borderline association with COX2 expression in that patients with metastases with COX2-positive tumors were alive for shorter periods of time compared with patients whose tumors had no COX2 expression (p<0.023, log-rank).
COX-2 expression has shown a significant correlation with tumor stage and hence is assumed to be a prognostic factor in our cohort of colorectal cancer patients.
Anticancer research 08/2013; 33(8):3137-43. · 1.71 Impact Factor
[show abstract][hide abstract] ABSTRACT: Aim: To verify the impact of breast cancer screening in women aged 40-49 years in one region of Brazil.
This is a cross-sectional study, targeted to asymptomatic women aged 40-69 years who had breast cancer screening mammography performed between January 2003 and December 2007. Logistic regression was used to estimate the risk of breast cancer by age groups (40-49, 50-59, 60-69 years).
Of the 27,133 screened women, 51.9% (14,082) were aged between 40-49 years. The odds ratio (OR) of breast cancer among the 45-49 year age cohort was not significantly different from that of 60 to 69-year-old women (OR=0.64; 95% Confidence Interval 0.39 to 1.03).
The risk of breast cancer among women aged 45 to 49 years is equivalent to that of women aged 60 to 69 years, indicating that breast cancer screening in this region of Brazil should start at the age of 45 years or immediately thereafter.
Anticancer research 06/2013; 33(6):2651-5. · 1.71 Impact Factor
[show abstract][hide abstract] ABSTRACT: To assess the prediction potential of a 5-biomarker panel for detecting high-risk human papillomavirus (HR-HPV) infections and/or cervical intraepithelial neoplasia (CIN) progression. Five biomarkers, lipocalin, plasminogen activator inhibitor-2, p300, interleukin-10, and stratifin, were assessed in cervical biopsies from 225 women of the Latin American Screening Study. Competing-risks regression models were constructed to assess their predictive power for (i) HR-HPV outcomes (negative, transient, or persistent infection) and (ii) CIN outcomes (no progression, incident CIN1, CIN2, or CIN3). p300, LCN2, stratifin were significantly associated with prevalent HR-HPV but lost their significance in multivariate analysis. In the multivariate model, only p300 was an independent predictor of CIN3 (odds ratio=2.63; 95% confidence interval, 1.05-6.61; P=0.039). In univariate competing-risks regression, lipocalin predicted permanent HR-HPV-negative status, but in the multivariate model, IL-10 emerged as a independent predictor of HPV-negative status (subhazard ratio=4.04; 95% confidence interval, 1.81-9.01; P=0.001). The clinical value of the panel in predicting longitudinal outcomes of HR-HPV infection and/or incident CIN is limited.
International journal of gynecological pathology: official journal of the International Society of Gynecological Pathologists 05/2013; · 2.07 Impact Factor
[show abstract][hide abstract] ABSTRACT: To perform a systematic review and formal meta-analysis of the literature reporting on HPV detection in bronchial squamous cell papillomas (SCP).
The literature was searched up to June 2012. The effect size was calculated as event rate (95% CI), with homogeneity testing using Cochran's Q and I(2) statistics. Meta-regression was used to test the impact of study-level covariates (HPV detection method, geographic origin) on effect size, and potential publication bias was estimated using funnel plot symmetry.
Fifteen studies were eligible, covering 89 bronchial SCPs from different geographic regions. Altogether, 38 (42.7%) cases tested HPV-positive; effect size 0.422 (95% CI: 0.311-0.542; fixed effects model), and 0.495 (95% CI: 0.316-0.675; random effects model). In meta-analysis stratified by i) HPV detection technique and ii) geographic study origin, the between-study heterogeneity was not significant for either; p = 0.348, and p = 0.792, respectively. In maximum likelihood meta-regression, HPV detection method (p = 0.150) and geographic origin of the study (p = 0.164) were not significant study-level covariates. Some evidence for publication bias was found only among in situ hybridization (ISH)-based studies and among studies from Europe, but with a negligible effect on summary effect size estimates. In sensitivity analysis, the meta-analytic results were robust to all one-by-one study removals.
In formal meta-regression, the variability in HPV detection rates reported in bronchial SCPs is not explained by the HPV detection method or geographic origin of the study.
[show abstract][hide abstract] ABSTRACT: There are no previous longitudinal studies on genotype-specific natural history of human papillomavirus (HPV) infections in oral mucosa of women.
In the Finnish Family HPV Study, 329 pregnant women were enrolled and followed up. HPV-genotyping of oral scrapings was performed with nested PCR and Multimetrix® test (Progen, Heidelberg, Germany). Incidence and clearance times and rates for each HPV-genotype identified in oral mucosa were determined. Predictors for incident and cleared HPV infections for species 7/9 genotypes were analyzed using Poisson regression model.
Altogether, 115 baseline HPV-negative women acquired incident oral HPV infection, and 79 women cleared their infection. HPV16 and multiple HPVs most frequently caused incident infections (65% and 12%) in 13.3 and 17.1 months respectively, followed by HPV58, HPV18 and HPV6 (close to 5% each) in 11-24 months. HPV58, HPV18 and HPV66 were the most common to clear. HPV6 and HPV11 had the shortest clearance times, 4.6 months and 2.5 months, and the highest clearance rates, 225.5/1000 wmr and 400/1000 wmr, respectively. The protective factors for incident oral HPV-species 7/9 infections were 1) new pregnancy during follow-up and 2) having the same sexual partner during FU. Increased clearance was related with older age and a history of atopic reactions, whereas previous sexually transmitted disease and new pregnancy were associated with decreased clearance.
HPV16 was the most frequent genotype to cause an incident oral HPV-infection. Low risk HPV genotypes cleared from oral mucosa more quickly than high risk HPV genotypes. Pregnancy affected the outcome of oral HPV infection.
PLoS ONE 01/2013; 8(1):e53413. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: Since first suggested (in 1983), the etiological role for human papillomavirus (HPV) in sinonasal carcinomas has been subject to constantly increasing interest. To perform systematic review and formal meta-analysis of the literature reporting on HPV detection in sinonasal squamous cell carcinomas (SCC), literature was searched through May 2012. The effect size was calculated as event rates (95% CI), with homogeneity testing using Cochran Q and I(2) statistics. Meta-regression was used to test the impact of study-level covariates (HPV detection method, geographic origin, papilloma type) on effect size, and potential publication bias was estimated using funnel plot symmetry. Thirty-five studies were eligible, covering 492 sinonasal SCCs from different geographic regions. Altogether, 133 (27.0%) cases tested HPV-positive; effect size 0.305 (95% CI, 0.260-0.355; fixed effects model), and 0.330 (95% CI, 0.249-0.423; random effects model. In meta-analysis stratified by (i) HPV detection technique and (ii) geographic study origin, the between-study heterogeneity was significant only for the latter; P = .526, and P = .0001, respectively. In maximum likelihood meta-regression, HPV detection method (P = .511) and geographic origin of the study (P = .812) were not significant study-level covariates. Some evidence for publication bias was found only among polymerase chain reaction-based studies and among studies from Europe and North America but with negligible effect on summary effect size estimates. In sensitivity analysis, all meta-analytic results were robust to all one-by-one study removals. In formal meta-regression, the variability in HPV detection rates reported in sinonasal SCCs was not explained by the HPV detection method or geographic origin of the study.
[show abstract][hide abstract] ABSTRACT: Clinical staging and histological grading after surgery have been the "gold standard" for predicting prognosis and planning for adjuvant therapy of colorectal cancer (CRC). With the recent development of molecular markers, it has become possible to characterize tumors at the molecular level. This is important for stage II and III CRCs, in which clinicopathological features do not accurately predict heterogeneity, e.g., in their tumor response to adjuvant therapy. In the present study, archival samples from 141 patients with stage I, II, III, or IV CRC treated during 1981-1990 at Turku University Hospital (Finland) were used (as microarray blocks) to analyze MUC2 expression by immunohistochemistry. Altogether, 49.7 % of all tumors were positive for MUC2. There was no significant correlation between MUC2 expression and age (P < 0.499), tumor invasion (P < 0.127), tumor staging (P < 0.470), histological grade (P < 0.706), lymph node involvement (P < 0.854), or tumor metastasis (P < 0.586). However, loss of MUC2 expression was significantly associated with disease recurrence (P < 0.031), tumor localization (P < 0.048), and with borderline significance with gender (P < 0.085). In univariate (Kaplan-Meier) survival analysis, positive MUC2 significantly predicted longer disease-free survival (DFS) and disease-specific survival (DSS) as well. However, in multivariate (Cox) survival analysis, MUC2 lost its power as an independent predictor of DFS and DSS. Our results implicate the value of MUC2 expression in predicting disease recurrence and long-term survival in CRC.
[show abstract][hide abstract] ABSTRACT: Since first suggested (in 1982), etiological role for human papillomavirus (HPV) in esophageal papillomas has aroused increasing interest. The objective of this study was to perform systematic review and formal meta-analysis of the literature reporting on HPV detection in esophageal squamous cell papillomas (ESCP). Literature was searched through May 2012. The effect size was calculated as event rates (95% CI), with homogeneity testing using Cochran's Q and I(2) statistics. Meta-regression was used to test the impact of study-level covariates (HPV detection method, geographic origin) on effect size, and potential publication bias was estimated using funnel plot symmetry. Thirty nine studies were eligible, covering 427 ESCPs from different geographic regions. Altogether, 132 (30.9%) cases tested HPV positive; effect size 0.375 (95% CI 0.319-0.434) using the fixed-effects (FE) model and 0.412 (95% CI 0.295-0.540) using the random-effects model. In meta-analysis stratified by (i) HPV detection technique and (ii) geographic study origin, the between-study heterogeneity was not significant (p = 0.071 and p = 0.105, respectively). In meta-regression, HPV detection method (p = 0.260) and geographic origin (p = 0.436) were not significant study-level covariates accounting for the heterogeneity in HPV prevalence. Some evidence for publication bias was found only for PCR-based studies, with a marginal impact on summary effect size estimates. In sensitivity analysis, all meta-analytic results were robust to all one-by-one study removals. In stratified meta-analysis and formal meta-regression, the variability in HPV detection rates in ESCPs is not explained by the HPV detection method or geographic origin of the study.
[show abstract][hide abstract] ABSTRACT: The features of Libyan patients with breast cancer have not been fully investigated. The aim of this study was to evaluate the expression patterns of estrogen (ER) and progesterone receptor (PR), as well as nuclear morphometric features, in patients with breast cancer, and to correlate them with clinicopathological features and prognosis.
Data for a total of 62 female Libyan patients with breast cancer, diagnosed between 2000 and 2006, were retrospectively studied. Their clinical and pathological data were collected and analysed. Immunohistochemical evaluation of ER and PR expression was also performed. Further more nuclear morphometry was carried out.
Of the 62 patients, disease in 10 was of the lobular type, 43 had invasive ductal and 9 had other carcinoma types; 47 out of 62 had lymph node involvement. Positive hormonal receptor expression was more common among those with lymph node-negative than lymph node-positive tumours. ER- and PR-positive patients appeared to have a better survival than ER- and PR-negative patients. The most significant difference, with respect to survival, was found between those bearing tumors with completely negative hormonal staining (J score 0) and those with positive staining (J score 1, 2 and 3). Larger nuclear size was associated with lymph node involvement and high-grade tumours (p<0.01 and p<0.0001, respectively), with shorter survival, larger tumour size and higher stage.
The cut-off points for defining the groups with good or worse prognosis might be set, between score 0 and 1 (corresponding to 1% or fewer positive cells). Patients with ER- and PR-positive cancer had better overall survival than patients with hormonal receptor-negative cancer. In our hospital setting, ER and PR expressions and mean nuclear area (MNA) in breast carcinoma may be prognostically useful markers in guiding future treatment in prospective studies.
Anticancer research 08/2012; 32(8):3485-93. · 1.71 Impact Factor
[show abstract][hide abstract] ABSTRACT: Strong expression of carbonic anhydrase IX (CA IX), hypoxia-inducible factor-1α (HIF-1α), ezrin and glucose transporter-1 (GLUT-1) were previously shown to be interrelated and to affect clinicopathological prognostic factors. In the current study, operative samples from 178 rectal cancer patients, 77 treated with short-course, 47 with long-course preoperative radiotherapy (RT), and 54 with no preoperative treatment, as well as 80 preoperative biopsies from the RT group were analysed using multivariate modelling in order to assess the role of these markers as predictors of disease outcome. Multivariate survival analysis revealed several sets of panels with the potential ability to identify patients at increased or decreased risk of dying from their disease or disease recurrence. The most remarkable panel, consisting of moderate/strong expression of CA IX, positive HIF-1α expression and negative/weak GLUT-1 expression in operative samples and negative/weak ezrin expression in preoperative biopsies was associated with 47.5-fold risk of death from this disease. These results should, however, be interpreted with caution due to the heterogeneity of the patient population in this retrospective study.
Anticancer research 08/2012; 32(8):3299-303. · 1.71 Impact Factor
[show abstract][hide abstract] ABSTRACT: Background: Since the first reports in 1982 suggesting an aetiological role for human papillomavirus (HPV) in a subset of oesophageal squamous cell carcinomas (ESCC), the literature reporting HPV detection in ESCC has expanded rapidly. However no formal meta-analysis of this literature has been published yet. The objective of this study was to perform a systematic review and formal meta-analysis of the literature reporting HPV detection in ESCC. Methods: MEDLINE and Current Contents were searched through March 2012. The effect size was calculated as event rates and their 95% confidence interval (95% CI), with homogeneity testing using Cochran's Q and I(2) statistics. Meta-regression was used to test the impact of study-level covariates (HPV detection method, geographic origin of study) on effect size, and potential publication bias was estimated using funnel plot symmetry (Begg and Mazumdar rank correlation, Egger's regression, and Duval and Tweedie's trim and fill method). Results: Of the 1177 abstracts found, 152 studies were determined to be eligible for this meta-analysis. These 152 studies covered a total of 10,234 ESCC cases, analysed by different HPV detection methods in different geographic regions. Of these 10,234 cases, 3135 (30.6%) tested HPV-positive, translating to an effect size of 0.372 (95% CI 0.360-0.384; fixed effects model) and 0.290 (95% CI 0.251-0.31; random effects model). When stratified by HPV detection technique, there was a significant heterogeneity between the studies, but importantly, the between-strata summary comparison was not significant (random effects model; p = 0.440). In contrast, there was significant heterogeneity between the studies from the different geographic regions. In the maximum likelihood meta-regression, HPV detection method was not a significant study-level covariate, in contrast to the geographic origin of the study, which had a significant impact (p = 0.00005) on the summary effect size estimates. No evidence for significant publication bias was found in funnel plot symmetry testing. In the sensitivity analysis, all meta-analytic results appeared robust to all (n = 151) one-by-one study removals. Conclusions: These meta-analysis results indicate that the reported wide variability in HPV detection rates in ESCC is not due to the HPV detection techniques, but is explained by the geographic origin of the study. These data substantiate the recently elaborated concept that ESCC might have a different aetiology in low-incidence and high-incidence geographic regions, HPV playing an important role only in the latter.
Scandinavian Journal of Infectious Diseases 07/2012; · 1.71 Impact Factor
[show abstract][hide abstract] ABSTRACT: The traditional staging system is currently inadequate for identifying those patients with colorectal carcinoma (CRC) who carry a high risk for poor outcome. In this study, the expression of E-cadherin was evaluated in CRC to determine its correlation with clinico-pathological variables, and association with disease outcome in patients with long-term follow-up. The present series consisted of tissue samples obtained from 230 patients with stage I, II, III, or IV CRC treated during 1981-1990 at Turku University Hospital. Archival paraffin-embedded samples were used to build up tissue microarray blocks, and E-cadherin expression was assessed by immunohistochemistry using an automated staining system. Different grading systems were tested for expression of E-cadherin. Fifty-nine percent of all tumors were positive for E-Cadherin. There was no significant correlation between E-cadherin expression and gender (p < 0.83), localization (p < 0.45), tumor invasion (p < 0.32), or histologic grade (p < 0.41). However, loss of E-cadherin expression was significantly associated with older age (p < 0.03) and lymph node involvement (p < 0.02), and with borderline significance with advanced stage (p < 0.09) and tumor metastasis (p < 0.09). In univariate (Kaplan-Meier) survival analysis, positive E-cadherin significantly (p = 0.009) predicted longer disease-free survival (DFS), and the same was true with disease-specific survival (DSS) as well (p = 0.007). In multivariate (Cox) survival analysis, E-cadherin retained its significance as independent predictor of DFS (HR = 1.56; 95% CI 1.01-2.42, p = 0.043), but not DSS. A sub-group analysis revealed that E-cadherin expression also predicts DFS (p < 0.01) and DSS (p < 0.04) in stage II CRC. Our results implicate the usefulness of E-cadherin expression in predicting disease recurrence and long-term survival in CRC.
[show abstract][hide abstract] ABSTRACT: BACKGROUND: In addition to the anogenital malignancies, human papillomavirus (HPV) has been linked to oropharyngeal cancer as an important risk factor in both men and women. Knowledge of oral HPV infection among males is needed to elucidate the transmission routes and potential for prevention. OBJECTIVE: To assess the prevalence, genotype distribution, and incidence of oral HPV infections among healthy Finnish men followed for 7 yr. DESIGN, SETTING, AND PARTICIPANTS: Oral scrapings for HPV testing were taken from 131 fathers-to-be (mean age: 28.9 yr) at baseline and at 2-mo, 6-mo, 12-mo, 24-mo, 36-mo, and 7-yr follow-up visits to detect prevalent and incident HPV infections. Purified DNA extracted from scrapings was used for HPV genotyping, with the Multimetrix kit (Progen Biotechnik, Heidelberg, Germany) detecting 24 genotypes. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Point prevalence, genotype distribution, and incident rates of oral HPV infections. Demographic data were collected using structured questionnaires, and covariates of incident oral HPV infections were analysed using uni- and multivariate Poisson regression (for panel data). RESULTS AND LIMITATIONS: The point prevalence of oral HPV infection fluctuated from 15.1% to 31.1% during the follow-up period. In total, 17 different HPV genotypes were found. At baseline, the single most frequent genotype among the HPV-positive samples was HPV16 (33.3%; 8 of 24), followed by HPV33 (12.5%) and HPV82 (12.5%). Multiple-type infections comprised 16.7% (4 of 24), HPV16 being involved in all combinations. For baseline-negative men, the mean time to the first incident infection ranged from 3.9 mo (HPV82) to 25.7 mo (HPV56). None of the demographic factors was a significant independent predictor of incident oral HPV infections in multivariate models. CONCLUSIONS: Detection of oral HPV DNA carriage in men is common, HPV16 being the most prevalent genotype. Oral mucosa may play a significant role in HPV transmission.
[show abstract][hide abstract] ABSTRACT: To assess human papillomavirus (HPV) prevalence and genotype distribution by age and cervical cytology/histology status among women undergoing routine gynecological examinations, and to discuss the possible impact on preventive strategies. Liquid-based cytology (LBC) samples were tested for HPV DNA, mRNA, and HPV genotypes. Women with atypical squamous cells of undetermined significance or greater (ASC-US+) and/or at least one positive HPV test were referred to colposcopy. Those with normal colposcopy results had biopsies taken at the 6 and 12 O'clock positions of the normal transformation zone. Of the 5002 women, 515 (10.3%) were <25 and 4487 (89.7%) were ≥25years old. Overall HPV prevalence varied between 10.1% and 16.1% depending on the assay. Risk factors for HPV infection included greater number of recent sexual partners, history of abnormal cervical pathology, age <25years, and smoking. HPV prevalence increased with the cytological and histological severity of cervical lesions. Prevalence of HPV 16/18 was 5.2% and 2.7% in women <25 and ≥25years old, respectively. HPV 16 was the type most strongly associated with a diagnosis of cervical intraepithelial neoplasia grade 3 or higher (CIN3+) (odds ratio=11.64 vs. HPV 16 absent, P<0.001). A high proportion of high-grade cervical lesions (60.6% of genotyping assay-positive CIN2+) were associated with HPV types 31, 33, 45, 52, or 58. These data indicate that almost all young women could benefit from HPV prophylactic vaccination, but confirm the need for continued cervical screening and highlight the potential benefit of future vaccines targeting a wider range of HPV types.
[show abstract][hide abstract] ABSTRACT: We sought to evaluate the performance of diagnostic tools to establish an affordable setting for early detection of cervical cancer in developing countries. We compared the performance of different screening tests and their feasibility in a cohort of over 12,000 women: conventional Pap smear, liquid-based cytology, visual inspection with acetic acid (VIA), visual inspection with Iodine solution (VILI), cervicography, screening colposcopy, and high-risk human papillomavirus (HPV) testing (HR-HPV) collected by physician and by self-sampling. HR-HPV assay collected by the physician has the highest sensitivity (80 %), but high unnecessary referrals to colposcopy (15.1 %). HR-HPV test in self-sampling had a markedly lower (57.1 %) sensitivity. VIA, VILI, and cervicography had a poor sensitivity (47.4, 55, and 28.6 %, respectively). Colposcopy presented with sensitivity of 100 % in detecting CIN2+, but the lowest specificity (66.9 %). Co-testing with VIA and VILI Pap test increased the sensitivity of stand-alone Pap test from 71.6 to 87.1 % and 71.6 to 95 %, respectively, but with high number of unnecessary colposcopies. Co-testing with HR-HPV importantly increased the sensitivity of Pap test (to 86 %), but with high number of unnecessary colposcopies (17.5 %). Molecular tests adjunct to Pap test seems a realistic option to improve the detection of high-grade lesions in population-based screening programs.
Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 05/2012; 460(6):577-85. · 2.68 Impact Factor