M Sideri

IEO - Istituto Europeo di Oncologia, Milano, Lombardy, Italy

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Publications (81)185.71 Total impact

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    ABSTRACT: Analytical and clinical performance validation is essential before introduction of a new HPV assay into clinical practice. This study compares the new BD Onclarity™ HPV assay, which detects E6/E7 DNA from 14 high-risk HPV types, to the HC2 HPV DNA test, to concurrent cytology and histology results, in order to evaluate its performance in detecting high-grade cervical lesions. A population of 567 women: 325 with ≥ASCUS and any HC2 result, and 242 with both negative cytology and HC2 results were prospectively enrolled for the study. The overall agreement between Onclarity and HC2 was 94.6% (95% Confidence Intervals (CI):92.3% - 96.2%). In this population with a high prevalence of disease the relative sensitivities (versus adjudicated CIN2+ histology endpoints) of the Onclarity and HC2 were 95.2% (95% CI: 90.7% - 97.5%) and 96.9 (95%CI: 92.9% - 98.7%) respectively, and the relative specificities were 50.3% (95% CI: 43.2% - 57.4%) for BD and 40.8% (95% CI: 33.9%, 48.1%) for HC2. These results indicate that BD Onclarity™ HPV assay has comparable sensitivity with HC2 with a trend to an increased specificity. Moreover, as Onclarity gives the chance to discriminate between the different genotypes, we calculated the prevalence and the absolute risk of CIN2+: HPV 16 was the most prevalent genotype (19.8%) with an absolute risk of CIN2+ of 77.1%. Copyright © 2015, American Society for Microbiology. All Rights Reserved.
    Journal of clinical microbiology 04/2015; DOI:10.1128/JCM.00246-15 · 4.23 Impact Factor
  • Journal of Lower Genital Tract Disease 04/2015; 19(2):e47-e48. DOI:10.1097/LGT.0000000000000091 · 1.11 Impact Factor
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    ABSTRACT: BACKGROUND Testing for the presence of the human papillomavirus (HPV) is widely accepted for triaging Papanicolaou cytology results categorized as atypical squamous cells of undetermined significance (ASC-US). In contrast, HPV testing has limited use in triaging cytological low-grade squamous intraepithelial lesions (LSILs) due to prevalence rates of typically >80%. In the current study, the authors assessed the diagnostic performance of p16/Ki-67 dual-stained cytology in triaging ASC-US and LSIL cases within the prospective, multicentric Primary ASC-US LSIL Marker Study (PALMS).METHODSA total of 575 ASC-US cases and 529 LSIL cases from a cohort of 27,349 women who were prospectively enrolled into the PALMS study in 5 European countries were tested with p16/Ki-67 dual-stained cytology and Hybrid Capture 2 (HC2) HPV testing. Colposcopy-guided biopsy results of cervical intraepithelial neoplasia of grade 2 or worse (CIN2+) were used as clinical endpoints.RESULTSp16/Ki-67 dual-stained cytology demonstrated comparable (ASC-US: 94.4% for dual-stained cytology vs 100% for HC2 testing; P = .317) or lower (LSIL: 85.7% for dual-stained cytology vs 98.4% for HC2 testing; P = .005) sensitivity for CIN2+, but higher levels of specificity compared with HC2 HPV testing in both ASC-US (78.7% vs 60.4%; P<.001) and LSIL (53.3% vs 15.6%; P<.001) cases. Positive predictive values for CIN2+ were substantially higher for dual-stained cytology versus HC2 HPV testing, especially in LSIL, and in ASC-US cases for women aged <30 years.CONCLUSIONS The clinical usefulness and efficiency of triaging women with ASC-US or LSIL Papanicolaou cytology results by p16/Ki-67 dual-stained cytology testing has been confirmed in this prospective, pan-European study. The high positive predictive value of dual-stained cytology for the presence of high-grade CIN may help to reduce the number of unnecessary colposcopy referrals. Cancer (Cancer Cytopathol) 2015. © 2015 American Cancer Society.
    Cancer Cytopathology 04/2015; 123(6). DOI:10.1002/cncy.21542 · 3.81 Impact Factor
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    ABSTRACT: Background:We performed a multicentre randomised controlled trial to evaluate the effect on participation in organised screening programmes of a self-sampling device mailed home or picked up at a pharmacy compared with the standard recall letter.Methods:Women aged 30-64 non-responding to screening invitation were eligible. Response rate to first invitation ranged from 30% to 60% between centres. The control was the standard reminder letter to undergo the test used by the programme (Pap test in three centres and HPV DNA test in three other centres). Home mailing of the self-sampler was preceded by a letter with a leaflet about HPV. The analysis was intention-to-treat.Results:In all, 14 041 women were randomised and recruited: 5012 in the control arm, 4516 to receive the self-sampler at home, and 4513 to pick up the self-sampler at a pharmacy. Participation was 11.9% in the control, 21.6% (relative participation: 1.75; 95% CI 1.60-1.93) in home, and 12.0% (relative participation: 0.96; 95% CI 0.86-1.07) in the pharmacy arms, respectively. The heterogeneity between centres was high (excess heterogeneity of that expected due to chance, i.e., I(2), 94.9% and 94.1% for home and pharmacy arm, respectively). The estimated impact on the overall coverage was +4.3% for home mail self-sampling compared with +2.2% for standard reminder.Conclusions:Home mailing of self-sampler proved to be an effective way to increase participation in screening programmes, even in those with HPV as primary testing. Picking up at pharmacies showed effects varying from centre to centre.British Journal of Cancer advance online publication, 29 January 2015; doi:10.1038/bjc.2015.11 www.bjcancer.com.
    British Journal of Cancer 01/2015; 112(4). DOI:10.1038/bjc.2015.11 · 4.82 Impact Factor
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    ABSTRACT: OBJECTIVE: A post hoc analysis to determine the diagnostic yield of random biopsy in detecting high-grade cervical disease in women with negative colposcopy. METHODS: The ATHENA (Addressing the Need for Advanced HPV Diagnostics) trial screened more than 47,000 women with cytology and high-risk human papillomavirus (HPV) DNA genotyping. Colposcopy was performed in all women with abnormal cytology or positive HPV results. A single random biopsy was taken at the squamocolumnar junction if colposcopy was adequate and no lesions were identified. RESULTS: The random biopsy diagnosed 20.9% (81/388, 95% confidence interval [CI] 16.9-25.3%) and 18.9% (45/238, 95% CI 14.1-24.5%) of the total cervical intraepithelial neoplasia (CIN) grade 2 or worse and grade 3 or worse, respectively. This additional disease was detected in both HPV 16 or 18+ and for 12 other high-risk HPV+ women. For HPV 16 or 18, the absolute risk for detection of CIN 2 or worse on random biopsy in the overall population was 13.1% (40/305, 95% CI 9.8-17.4%) and 8.2% (25/305, 95% CI 5.6-11.8%) for CIN 3 or worse. By contrast, the absolute risk for 12 other high-risk HPV+ women was 3.5% (29/820, 95% CI 2.5-5%) and 1.7% (14/820, 95% CI 1.0-2.8%) for CIN 2 or worse and CIN 3 or worse, respectively. CONCLUSION: A single random biopsy increased the detection of high-grade disease when no lesions were visualized at colposcopy. The absolute risks of disease associated with the random biopsy were highest for women positive for genotype 16 or 18. Our study supports performing a random biopsy in women undergoing colposcopy without visible lesions, particularly in those positive for HPV 16 or 18.
    Obstetrics and Gynecology 09/2014; 124(4). DOI:10.1097/AOG.0000000000000458 · 4.37 Impact Factor
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    ABSTRACT: Human papillomavirus 45 (HPV45) is a member of the HPV18-related alpha-7 species and accounts for approximately 5% of all cervical cancer cases worldwide. This study evaluated the genetic diversity of HPV45 and the association of HPV45 variants with the risk of cervical cancer by sequencing the entire E6 and E7 open reading frames of 300 HPV45-positive cervical samples from 36 countries. A total of 43 HPV45 sequence variants were identified that formed 5 phylogenetic sublineages, A1, A2, A3, B1, and B2, the distribution of which varied by geographical region. Among 192 cases of cervical cancer and 101 controls, the B2 sublineage was significantly overrepresented in cervical cancer, both overall and in Africa and Europe separately. We show that the sequence analysis of E6 and E7 allows the classification of HPV45 variants and that the risk of cervical cancer may differ by HPV45 variant sublineage. IMPORTANCE: This work describes the largest study to date of human papillomavirus 45 (HPV45)-positive cervical samples and provides a comprehensive reference for phylogenetic classification for use in epidemiological studies of the carcinogenicity of HPV45 genetic variants, particularly as our findings suggest that the B2 sublineage of HPV45 is associated with a higher risk of cervical cancer.
    Journal of Virology 04/2014; 88(8):4514-4521. DOI:10.1128/JVI.03534-13 · 4.65 Impact Factor
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    ABSTRACT: BACKGROUND: Pap cytology is known to be more specific but less sensitive than testing for human papillomavirus (HPV) for the detection of high-grade cervical intraepithelial neoplasia (CIN2+). We assessed whether p16/Ki-67 dual-stained cytology, a biomarker combination indicative of transforming HPV infections, can provide high sensitivity for CIN2+ in screening while maintaining high specificity. Results were compared with Pap cytology and HPV testing. METHODS: A total of 27,349 women 18 years or older attending routine cervical cancer screening were prospectively enrolled in five European countries. Pap cytology, p16/Ki-67 immunostaining, and HPV testing were performed on all women. Positive test results triggered colposcopy referral, except for women younger than 30 years with only positive HPV test results. Presence of CIN2+ on adjudicated histology was used as the reference standard. Two-sided bias-corrected McNemar P values were determined. RESULTS: The p16/Ki-67 dual-stained cytology positivity rates were comparable with the prevalence of abnormal Pap cytology results and less than 50% of the positivity rates observed for HPV testing. In women of all ages, dual-stained cytology was more sensitive than Pap cytology (86.7% vs 68.5%; P < .001) for detecting CIN2+, with comparable specificity (95.2% vs 95.4%; P = .15). The relative performance of the tests was similar in both groups of women: younger than age 30 and 30 years or older. HPV testing in women 30 years or older was more sensitive than dual-stained cytology (93.3% vs 84.7%; P = .03) but less specific (93.0% vs 96.2%; P < .001). CONCLUSIONS: The p16/Ki-67 dual-stained cytology combines superior sensitivity and noninferior specificity over Pap cytology for detecting CIN2+. It suggests a potential role of dual-stained cytology in screening, especially in younger women where HPV testing has its limitations.
    JNCI Journal of the National Cancer Institute 10/2013; 105(20):1550-7. DOI:10.1093/jnci/djt235. · 15.16 Impact Factor
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    ABSTRACT: Pap cytology is known to be more specific but less sensitive than testing for human papillomavirus (HPV) for the detection of high-grade cervical intraepithelial neoplasia (CIN2+). We assessed whether p16/Ki-67 dual-stained cytology, a biomarker combination indicative of transforming HPV infections, can provide high sensitivity for CIN2+ in screening while maintaining high specificity. Results were compared with Pap cytology and HPV testing. A total of 27349 women 18 years or older attending routine cervical cancer screening were prospectively enrolled in five European countries. Pap cytology, p16/Ki-67 immunostaining, and HPV testing were performed on all women. Positive test results triggered colposcopy referral, except for women younger than 30 years with only positive HPV test results. Presence of CIN2+ on adjudicated histology was used as the reference standard. Two-sided bias-corrected McNemar P values were determined. The p16/Ki-67 dual-stained cytology positivity rates were comparable with the prevalence of abnormal Pap cytology results and less than 50% of the positivity rates observed for HPV testing. In women of all ages, dual-stained cytology was more sensitive than Pap cytology (86.7% vs 68.5%; P < .001) for detecting CIN2+, with comparable specificity (95.2% vs 95.4%; P = .15). The relative performance of the tests was similar in both groups of women: younger than age 30 and 30 years or older. HPV testing in women 30 years or older was more sensitive than dual-stained cytology (93.3% vs 84.7%; P = .03) but less specific (93.0% vs 96.2%; P < .001). The p16/Ki-67 dual-stained cytology combines superior sensitivity and noninferior specificity over Pap cytology for detecting CIN2+. It suggests a potential role of dual-stained cytology in screening, especially in younger women where HPV testing has its limitations.
    CancerSpectrum Knowledge Environment 10/2013; 105(20). DOI:10.1093/jnci/djt235 · 15.16 Impact Factor
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    ABSTRACT: Background: Hysterectomy plus salpingo-oophorectomy represents the standard treatment for patients with well-differentiated endometrial cancer (EC) limited to the endometrium. It is estimated that over 5% of EC are diagnosed in nulliparous women aged 35-44 years. In addition, EC can affect obese women with diabetes, hypertension and other comorbidities increasing the surgical risk. Methods : This article reviews the English literature in PubMed regarding hormonal treatment of EC. Results: Use of hormonal therapies has resulted in complete remission in 60-70%; many of these women were able to achieve full-term pregnancies, and in case of contraindication to surgery, resection could be avoided. Several topics, however, such as patient selection, interobserver histologic evaluation, the type/duration of hormonal treatment, modality of evaluation before treatment and surveillance after treatment, which are still subject to controversy, are therefore discussed in this paper. Conclusion : Uterus-sparing treatment of well-differentiated EC limited to the endometrium is feasible and has acceptable efficacy in women with increased surgical risk or those who wish to preserve their fertility. Although the methods applied to determine disease extent beyond the endometrium are still unsatisfactory, patient selection is a crucial factor determining the outcome of treatment. However, women must be fully informed about the possibility of treatment failure and the necessity of a close follow-up after therapy.
    Gynecologic and Obstetric Investigation 03/2013; 75(3):145-151. DOI:10.1159/000349891 · 1.25 Impact Factor
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    ABSTRACT: OBJECTIVE: The quality of first surgery is one of the most important prognostic factors in ovarian cancer patients. Pre-surgical distinction of benign and malignant pelvic mass plays a critical role in ovarian cancer management and survival. The aim of this study was to evaluate the clinical performance of ROMA algorithm and of CA125 and HE4 in the triage of patients with a pelvic mass undergoing surgery, in order to discriminate benign from malignant disease. METHODS: Three hundred and forty-nine pre- and post-menopausal women, aged 18years or older undergoing surgery because of a pelvic mass were enrolled: serum concentrations of CA125 and HE4 were determined and ROMA was calculated for each sample. RESULTS: Median serum CA125 and HE4 levels were higher in patients with EOC compared to subjects with benign disease (p<0.0001). The resultant accuracy (using Receiver Operating Characteristics, ROC Area) values for HE4, CA125 and ROMA showed a good performance ranging from 89.8% for CA125 in pre-menopausal patients to 93.3% for ROMA in post-menopausal patients: AUC for ROMA resulted significantly higher in comparison to CA125 alone (93.3% vs 90.3%, p=0.0018) in post menopausal patients. A sub-analysis considering the 40 patients with endometrioid disease showed the highest accuracy of HE4 in these patients. CONCLUSIONS: Data presented confirm the accuracy of HE4 and of the ROMA algorithm in the distinction of ovarian carcinoma from benign disease, with a trend towards better performance for ROMA than for CA125 alone, statistically significant in postmenopausal patients.
    Gynecologic Oncology 11/2012; 128(2). DOI:10.1016/j.ygyno.2012.11.026 · 3.69 Impact Factor
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    ABSTRACT: The EUROGIN 2011 roadmap reviews the current burden of human papillomavirus (HPV)-related morbidity, as well as the evidence and potential practice recommendations regarding primary and secondary prevention and treatment of cancers and other disease associated with HPV infection. HPV infection causes ~600,000 cases of cancer of the cervix, vulva, vagina, anus and oropharynx annually, as well as benign diseases such as genital warts and recurrent respiratory papillomatosis. Whereas the incidence of cervical cancer has been decreasing over recent decades, the incidence of anal and oropharyngeal carcinoma, for which there are no effective screening programs, has been rising over the last couple of decades. Randomized trials have demonstrated improved efficacy of HPV-based compared to cytology-based cervical cancer screening. Defining the best algorithms to triage HPV-positive women, age ranges and screening intervals are priorities for pooled analyses and further research, whereas feasibility questions can be addressed through screening programs. HPV vaccination will reduce the burden of cervical precancer and probably also of invasive cervical and other HPV-related disease in women. Recent trials demonstrated that prophylactic vaccination also protects against anogenital HPV infection, anogenital intraepithelial lesions and warts associated with vaccine types, in males; and anal HPV infection and anal intraepithelial neoplasia in MSM. HPV-related oropharyngeal cancer could be treated less aggressively because of better survival compared to cancers of the oropharynx unrelated to HPV. Key findings in the field of cervical cancer prevention should now be translated in cost-effective strategies, following an organized approach integrating primary and secondary prevention, according to scientific evidence but adapted to the local situation with particular attention to regions with the highest burden of disease.
    International Journal of Cancer 11/2012; 131(9):1969-82. DOI:10.1002/ijc.27650 · 5.01 Impact Factor
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    ABSTRACT: Objective The aim of this study is to describe the prevalence of HPV types in invasive cervical cancers in Italy from 1996 to 2008. Methods A pooled analysis of the three largest case series typed to date was performed. HPV typing was performed on paraffin-embedded slices. Molecular analyses were performed in four laboratories. Multivariate analyses were performed to test the associations between calendar time, age, and geographical area and the proportion of types 16/18. Results Out of 574 cancers, 24 (4.2%) were HPV negative. HPV 16 and 18 were responsible for 74.4% (378/508) and 80.3% (49/61) of the squamous cancers and adenocarcinomas, respectively. Other frequent types were 31 (9.5%), 45 (6.4%), and 58 (3.3%) for squamous cancers and 45 (13.3%), 31, 35, and 58 (5.0%) for adenocarcinomas. The proportion of HPV 16 and/or 18 decreased with age (p-value for trend <0.03), while it increased in cancers diagnosed in more recent years (p-value for trend < 0.005). Conclusions The impact of HPV 16/18 vaccine on cervical cancer will be greater for early onset cancers. In vaccinated women, screening could be started at an older age without reducing protection.
    Infectious Agents and Cancer 10/2012; 7(1):26. DOI:10.1186/1750-9378-7-26 · 2.07 Impact Factor
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    ABSTRACT: New colposcopy terminology was prepared by the Nomenclature Committee of the International Federation of Cervical Pathology and Colposcopy after a critical review of previous terminologies, online discussions, and discussion with national colposcopy societies and individual colposcopists. This document has been expanded to include terminology of both the cervix and vagina. The popular terms "satisfactory colposcopy" and "unsatisfactory colposcopy" have been replaced. The colposcopic examination should be assessed for three variables: 1) adequate or inadequate, with the reason given; 2) squamocolumnar junction visibility; and 3) transformation zone type. Other additions were the localization of the lesion to either inside or outside the transformation zone and determinants of size as well as location of cervical lesions. Two new signs were included in the terminology-the "inner border sign" and "ridge sign." The following definitions have been added: congenital transformation zone, polyp (ectocervical or endocervical), stenosis, congenital anomaly, and posttreatment consequence. In addition, the terminology includes standardization of cervical excision treatment types and cervical excision specimen dimensions. The International Federation of Cervical Pathology and Colposcopy recommends that the 2011 terminology replace all others and be implemented for diagnosis, treatment, and research.
    Obstetrics and Gynecology 07/2012; 120(1):166-72. DOI:10.1097/AOG.0b013e318254f90c · 4.37 Impact Factor
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    ABSTRACT: The large amount of literature published over the last two decades on human papillomavirus (HPV)-DNA testing has definitely demonstrated the association between high-risk viral genotypes (hrHPV) and cervical cancer. Moreover, hrHPV-DNA testing has shown excellent performance in several clinical applications, from screening settings to the follow-up of treated patients, compared to conventional cytology or colposcopy options. On the other hand, when a huge number of reports are published on the same subject in a relatively short period of time, with many variations in settings, study designs and applications, the result is often confusion and decreased comprehension by readers. In daily office practice, several different situations (in symptomatic or asymptomatic women) can be positively managed by the correct use of hrHPV-DNA testing. Validated hrHPV-DNA testing and, specifically, the HC2® assay, due to its excellent sensitivity and negative predictive value together with optimal reproducibility, currently represent a powerful tool in the clinician's hands to optimally manage several situations related to HPV infection and the potential development of cervical cancer.
    ecancermedicalscience 06/2012; 6:258. DOI:10.3332/ecancer.2012.258 · 1.20 Impact Factor
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    ABSTRACT: This study aimed to present the clinical and colposcopic terminology of the vulva (including the anus) of the International Federation of Cervical Pathology and Colposcopy. The terminology has been developed by the International Federation of Cervical Pathology and Colposcopy Nomenclature Committee during 2009-2011. The terminology is part of a comprehensive terminology of the lower genital tract, allowing for standardization of nomenclature by colposcopists, clinicians, and researchers taking care of women with lesions in these areas. The terminology includes basic definitions and normal findings that are important for the clinician lacking experience with management of vulvar disease. This terminology introduces definitions for abnormal findings recently accepted by the International Society for the Study of Vulvovaginal Disease and includes patterns to identify malignancy. The terminology differs from past terminologies in that it includes colposcopic patterns and anal colposcopy. Nevertheless, the role of the colposcope in the management of vulvar disease is limited.
    Journal of Lower Genital Tract Disease 05/2012; 16(3):290-5. DOI:10.1097/LGT.0b013e31825934c7 · 1.11 Impact Factor
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    ABSTRACT: OBJECTIVE OF THE PROJECT: The introduction of the HPV test as a primary screening test will cause important changes in the screening system based on cytology. The purposes of this report are: to define the best screening policies with HPV-based screening on the basis of the resulting efficacy and of undesired effects; comparing them to cytology-based screening; to identify their best conditions of application; to evaluate economic cost, feasibility and impact on the organisation of services of such policy in the Italian situation. This report contains a section on efficacy and undesired effects based on a systematic review of literature conducted in strict coordination with the preparation of a supplement to the European Guidelines for quality assurance in cervical cancer screening. This chapter corresponds to a preliminary version of the chapter of the European Guidelines on primary screening with HPV. The sections on costs, impact on organisation, and social, ethical and legal impact reflect the Italian situation; they are based on a review of the available Italian data (including unpublished data, mainly from on-going pilot projects) and on a structured analysis of what will result if the proposed protocol is applied to the Italian situation. Efficacy and undesired effects. There is clear scientific evidence that a screening based on validated tests for the DNA of oncogenic HPV as primary test and applying an appropriate protocol is more effective than screening based on cytology in preventing invasive cancers of the uterine cervix. In addition, it entails a limited--if any--increase of the undesired effects both in terms of unneeded referral to diagnostic work-up and in terms of over-diagnosis and consequent overtreatment of spontaneously regressive lesions. The crucial elements of such protocol are the followings: HPV-positive women are not to be directly referred to colposcopy, but the use of triage systems is essential. The currently recommendable method is based on performing cytology in HPV positive women. If the result of this test is abnormal, the woman is immediately referred to colposcopy; if cytology is normal, the woman is invited to repeat a new HPV test after one year. In case such a test is still positive, the woman is referred to colposcopy; in case of negative result, the woman will be re-invited for a new screening round at the regular interval. In organised population-based screening programmes the interval after a negative primary HPV test should be at least 5 years. There is evidence that the 5-year cumulative risk of high-grade CIN after a negative HPV test is lower than the 3-year risk after a normal cytology. On the other hand, the probability of unneeded colposcopies and treatments would plausibly be relevant with 3-year intervals after a negative HPV test. HPV-based screening should not start before 30-35 years. There is evidence that below 30 years HPV-based screening leads to an increased overdiagnosis of CIN2 that would regress spontaneously, with consequent overtreatment. Some increase in overdiagnosis is plausible also between 30 and 34 years. Below such ages, cytological screening is the recommended test. Only tests for the DNA of oncogenic HPV, validated according to the European guidelines as for sensitivity and specificity for high-grade lesions, should be applied. There is no evidence that double testing with cytology and HPV is more protective than stand-alone HPV as primary test, although it entails a small and not relevant increase in sensitivity vs stand-alone HPV. On the contrary, there is evidence that double testing causes a substantial increase in referral to colposcopy and a decrease in its PPV. For this reason, if HPV is used as primary screening test, it is recommended not to add cytology in parallel. Cost and economic evaluation. It is estimated that, if the protocol described is applied, in the current Italian situation the overall costs of HPV-based screening are lower than those of conventional cytological screening applied at the current 3-year intervals, although the cost of each screening round is higher. Impact on organization. For reasons of quality and cost, both the interpretation of cytology and HPV testing require a centralisation. This need is particularly strong, in terms of costs, for HPV test execution. It is therefore recommended to perform the HPV test in a limited number of reference laboratories of large size. This also makes monitoring and evaluating the spontaneous activity easier. HPV-based screening entails problems of organisation related to the need of triage, to complex protocols and to reconversion of the activities of cytological interpretation. Social, ethical and legal impact. The communication of the result of the HPV test to women, particularly if positive, is a further crucial aspect in order to reduce not only the emotional impact, but also the possible risks that women are inappropriately managed or lost to follow-up. Great efforts must be put in the education of healthcare professionals, both directly involved in organised programmes or not, particularly private gynaecologists and general practitioners. In conclusion, the crucial requirement to introduce HPV-based screening programmes is the capacity to guarantee the application of appropriate screening protocols. If protocols do not respect the criteria described above they can cause relevant increase of undesired effects and costs compared to cytology-based screening. Therefore they should be avoided, except in studies able to provide clear evidence about human and economic costs. For this purpose, correct education and information both to healthcare professionals and to the population is needed. In the Italian situation, where organised screening and a relevant spontaneous activity coexist, their interaction is crucial. Actions directed to integrate them and to guarantee as more uniformity of interventions as possible are needed, in particular through the integration of registries and thorough monitoring and a progressive homogenization of protocols. In order to grant the safety of transition, it is needed that the HPV-based organised screening activities are strictly monitored and that the National Centre for Screening Monitoring (ONS) ensures coordination. Knowledge about HPV based screening is still rapidly evolving. It is possible that currently on-going researches suggest changes to the optimal protocols in the next few years, particularly as for the management of HPV positive women. In addition, studies on the validation of new assays were recently published and others are expected. It is suggested to exploit the organised screening activity to produce scientific evidence, in order to clarify the still uncertain aspects of optimal protocols. Different protocols in terms of screening intervals, age of application and management of HPV positive women should be studied in the frame of controlled implementation, through multicentre projects coordinated by ONS. Finally, it is suggested the creation of a National working group to promptly update the recommendations for screening and the list of assays to be considered as validated. On the bases of the results obtained in the first vaccinated cohorts reaching the screening age, for the future, it will be crucial to deliver specific recommendations to the population vaccinated against HPV during adolescence.
    Epidemiologia e prevenzione 05/2012; 36(3-4 Suppl 1):e1-72. · 1.46 Impact Factor
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    ABSTRACT: Human papillomavirus (HPV) testing is more sensitive and has higher negative predictive value (NPV) than the Pap test for the detection of cervical intraepithelial neoplasia (CIN) in patients with atypical squamous cells of undetermined significance (ASCUS) cytology, but has low specificity, leading to high referral rates to second-level triage. Our goal was to identify the prognostic significance of HPV viral load figures. We evaluated whether a correlation between viral load, expressed as relative light units/cutoff (RLU/CO), and the severity of cervical lesions existed in 614 ASCUS cases. Hybrid Capture 2 (HC2®) RLU/CO values, categorised into five classes, were correlated to clinical outcomes and statistically analysed. A significant correlation (p < 0.0001) was observed between increasing RLU values and the prevalence of high-grade CIN (CIN2/CIN3). The mean RLU values for negative, low-grade and high-grade lesions were 68.1, 172.5 and 1,020.0 RLU/CO, respectively (p < 0.0001). CIN2/CIN3 ranged from 4% for 0 < RLU/CO values ≤ 1, to 5% for 1 < RLU/CO values ≤ 10, to 9% for 10 < RLU/CO values ≤ 100, to 23% for 100 < RLU/CO values ≤ 1,000 and to 48% when RLU/CO values were >1,000 (p < 0.05). The HPV viral load in ASCUS cases significantly correlates with the severity of cervical cancer precursors. These data may have prognostic value, as they significantly correlate with the probability of a CIN2+ .
    European Journal of Clinical Microbiology 03/2012; 31(9):2401-6. DOI:10.1007/s10096-012-1582-1 · 2.67 Impact Factor
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    ABSTRACT: The correlation between high-risk HPV-DNA viral load, expressed as relative light units (RLU) values obtained from the Hybrid Capture 2 (HC2) test, and the prevalence of CIN2/CIN3 was investigated and statistically analyzed in 614 ASC-US consecutive cases. Cases were categorized into three groups according to RLU values: "low-grade positivity", "intermediate positivity" and "high-grade positivity", and the prevalence of CIN2/CIN3 was evaluated in the single groups and compared among them. CIN/CIN3 rates demonstrated a significant (p < 0.001) increase with a direct correlation with increasing RLU values: 4.6% (RLU from 1.0 to 10.0), 9.1% (RLU from 11.0 to 100.0) and 32.2% (RLU > 100.0) respectively. The prevalence of CIN2/CIN3 between the group with RLU < 10.0 (4.6%) and the group with RLU > 10 (24.2%) showed statistical significance (p = 0.0002). Increasing hrHPV viral load significantly correlates with increasing prevalence of CIN2/CIN3 in ASC-US cases.
    European journal of gynaecological oncology 01/2012; 33(3):261-4. · 0.60 Impact Factor
  • Lucas Minig · Dorella Franchi · Mario Sideri
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    ABSTRACT: Uterus-sparing hormonal treatment of patients affected by well-differentiated endometrial carcinoma is becoming an important issue. High doses of oral progesterone is the most common drug for treating these patients. However, the levonorgestrel intruterine device has recently been shown to be effective in some patients with a strong desire for future pregnancies or with high surgical risk. Local administration of the hormone therapy, moreover, can avoid the most frequent adverse side effects caused by oral progesterone. Patient selection to exclude preexisting myoinvasive or distant disease is a crucial, although imperfect, prerequisite. Given the risks of disease progression or relapse, close follow-up during and after treatment to monitor failures is crucial. Therefore, in this article we review the current evidence regarding the efficacy of the levonorgestrel-intrauterine device for treating well-differentiated endometrial carcinoma limited to the endometrium.
    Expert Review of Obstetrics &amp Gynecology 06/2011; 6(4):423-429. DOI:10.1586/eog.11.35
  • M Sideri · L Minig · D Franchi · C Casadio · S Boveri · L Bocciolone
    Annals of Oncology 03/2011; 22(3):749. DOI:10.1093/annonc/mdq765 · 6.58 Impact Factor

Publication Stats

2k Citations
185.71 Total Impact Points

Institutions

  • 1999–2015
    • IEO - Istituto Europeo di Oncologia
      • • Division of Preventive Gynecology
      • • Division of Epidemiology and Biostatistics
      Milano, Lombardy, Italy
  • 2012
    • Bar Ilan University
      Gan, Tel Aviv, Israel
  • 1989–1998
    • University of Milan
      Milano, Lombardy, Italy
  • 1982
    • INO - Istituto Nazionale di Ottica
      Florens, Tuscany, Italy