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Background: High-risk (HR) Human Papilloma Virus (HPV) Tests for HPV detection differ in sensitivity and specificity. In this study, we evaluated the sensitivity and specificity of the HC2 HR HPV Test and the Cobas 4800 HPV Test in consecutive cervical samples collected from a referral population with a high prevalence of disease, using CIN2+ histology as clinical outcome., Methods: Ten thousand two-hundred and thirteen consecutive cervical samples were assayed for HR-HPV in the Laboratory Medicine Division of IEO: 5140 from January 2012 to June 2013 with HC2 and 5073 from July 2013 to December 2014 with the Cobas HPV Test. These two assays differ in terms of target genes and testing methods., Results: The test positivity rates for HC2 and Cobas 4800 were 29.5% (1515/5135, 95% CI 28.3-30.8%) and 23.9% (1212/5069, 95% CI 22.7-25.1%), respectively. The detection rates of CIN2+ in the two time periods were 2.8% (145/5140, 95% CI 2.4-3.3%) and 1.6% (79/5073, 95% CI 1.2-1.9%), respectively. The sensitivity for CIN2+ for HC2 and Cobas 4800 was 95.2% (138/145, 95% CI 91.7-98.7%) and 93.7% (74/79, 95% CI 88.3-99.0%), respectively. The specificity for CIN2+ for HC2 and Cobas 4800 was 72.4% (3613/4990, 95% CI 71.2-73.6%) and 77.2% (3852/4990, 95% CI 76.0-78.4%), respectively. There were 23 cases of cancer in each of the two time periods. HC2 detected 100% (23/23). Cobas 4800 detected 82.6% (19/23)., Conclusions: The detection rate of CIN2+ was higher in the first period than in the second period. There was no significant difference in sensitivity of HC2 and Cobas 4800 in women with CIN2+. The specificity of CIN2+ using Cobas 4800 in the second period was higher than HC2 in the first period, probably due to the lower prevalence of CIN2+ in the second period.

Objective: To evaluate, from a gynecology perspective, the transition from cytology-based HPV screening to primary HPV screening., Methods: Studies examining switching from cytology-based screening to primary HPV-DNA testing with triaging of patients with positive test results were retrieved and reviewed, with a particular focus on screening in an Italian setting., Results: The increased complexity of patient-management decisions when implementing HPV-based screening was a critical issue discussed in the literature. The change in strategy represents a paradigm shift in moving from a medical perspective of identifying the disease in individual patients, to a public-healthcare perspective of excluding HPV from the healthy population and identifying a small sub-group of individuals at increased risk of HPV., Conclusion: With knowledge about HPV screening evolving rapidly, new programs and related algorithms need to be sufficiently flexible to be adjusted according to ongoing research and the validation of new assays. The establishment of a national working group (including epidemiologists, gynecologists, pathologists, and healthcare providers) will be necessary to properly implement and govern this important technical and cultural transition., (© 2016 International Federation of Gynecology and Obstetrics.)

Objectives: Little is known about the epidemiology of human papillomavirus (HPV) in Italy before the age of 25. At the European Institute of Oncology, a prospective observational study on cervical HPV infection in 18-year-old women undergoing quadrivalent HPV vaccination is ongoing., Methods: At the first visit before vaccination, all the young women answered an epidemiological questionnaire, and then, the presence of high-risk HPV (hrHPV) was tested. Samples positive for hrHPV were genotyped. Liquid-based cytology was done only to women declaring not to be virgins. Any positivity at cytology or HPV testing was completed with colposcopy and eventually biopsies., Results: Seven hundred and thirty women were enrolled. Two hundred sixty-six women were virgins; 7 (2.6%) of these resulted positive to hrHPV: 1 had HPV16 and CP6108, whereas the other 6 resulted negative at genotyping. Of the 464 nonvirgins, 61 (13.1%) were HPV positive: 19 had HPV16, 4 were positive to HPV18 with other hrHPVs, 25 to other hrHPVs, 7 to low-risk HPV, whereas 13 resulted negative at genotyping. HPV positivity was significantly associated to both smoking and having more than 3 partners. Cervical cytology was negative in 433 cases (93.3%), ASC-US in 10 cases (2.2%), low-grade squamous intraepithelial lesion in 20 cases (4.3%), and ASC-H in 1 case (0.2%). No CIN2+ was identified., Conclusions: Overall, we found a low positivity to HPV in this population; however, the rate of HPV positivity was significantly related to smoking and sexual life. The cytology result low-grade squamous intraepithelial lesion was more frequent than in the screening population, whereas no CIN2+ was identified, confirming the indication to avoid screening at this age.

Analytical and clinical performance validation is essential before introduction of a new human papillomavirus (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 Hybrid Capture II (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, including 325 with ≥ASCUS (where ASCUS stands for atypical cells of undetermined significance) and any HC2 result and 242 with both negative cytology and negative HC2 results, were prospectively enrolled for the study. The overall agreement between Onclarity and HC2 was 94.6% (95% confidence intervals [CI], 92.3% to 96.2%). In this population with a high prevalence of disease, the relative sensitivities (versus adjudicated cervical intraepithelial neoplasia grades 2 and 3 [CIN2+] histology endpoints) of the Onclarity and HC2 tests were 95.2% (95% CI, 90.7% to 97.5%) and 96.9% (95% CI, 92.9% to 98.7%), respectively, and the relative specificities were 50.3% (95% CI, 43.2% to 57.4%) for BD and 40.8% (95% CI, 33.9%, 48.1%) for HC2. These results indicate that the BD Onclarity HPV assay has sensitivity comparable to that of the HC2 assay, with a trend to an increased specificity. Moreover, as Onclarity gives the chance to discriminate between the different genotypes, we calculated the genotype 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.)

Objective: Strong evidences shows that HPV testing is more sensitive than cytology in detecting high-grade CIN. HPV test can be performed on samples collected by women themselves by means of self-sampling devices. This study compares the results of self-sampled HPV tests with the results of liquid based cytology (LBC)., Study Design: Seven hundred women scheduled for cervical cytology self-collected a cervicovaginal sample for HPV testing and then underwent a clinician-collected LBC at the European Institute of Oncology. The HPV and LBC results were compared with the McNemar test., Results: All HSIL (N=5) resulted hrHPV positive. LBC resulted LSIL or worse in 38 (5.4%) women (out of 700). Self-sampled HPV was positive in 96 women (13.7%). A LSIL or worse LBC result was found in 15 (2.5%) patients, out of the 604 hrHPV negative women and in 23 (24%) patients, out of the 96 hrHPV positive women. Positive cytology after a self-sampled HPV positive result had an Odds Ratio of 12.4 (95% CI: 5.8-26.6)., Conclusion: Self-collected HPV testing identifies a group of women at high risk of positive LBC and high grade SIL., (Copyright © 2014. Published by Elsevier Ireland Ltd.)

Objective: The rare occurrence of histology-proven cervical intraepithelial neoplasia grade 3 (CIN 3) or invasive cancer with a negative HC2 result is known. Tissue blocks of 37 cases of histology-diagnosed CIN 3+ with a concomitant negative HC2 test were genotyped to investigate the human papillomavirus (HPV) status within the lesion., Methods: We considered 1,976 cervical excision specimens performed with concomitant HC2 test. Of these, 37 histology-confirmed CIN 3+ resulted HC2 negative. Thirty-three paraffin blocks, derived by the cervical excision, could be genotyped for high- (HR) and low-risk (LR) HPV genotypes., Results: Detailed histology showed 30 CIN 3, 2 squamous cell invasive carcinomas, and 5 invasive adenocarcinomas. One specimen resulted not amplifiable at the genotyping. Twenty-two cases (68.7%) were positive for HR-HPV types, either in single (n = 17) or multiple HR-HPV infection (n = 5). Most of the HR-HPVs found were 16 or 18. Ten cases (31.3%) were negative for HR-HPV types; 5 of these were positive for probable HR-HPV types, not detectable with HC2 HR-probes, 1 was positive to LR-HPV types, while 1 had HPV-69/71. Three cases were negative for HPV DNA, either high or low risk., Conclusions: Of the rare cases of CIN 3+ lesions with concomitant negative HC2 test, 69% are true failures in HR-HPV detection. One third of HC2-negative CIN 3+ is related to the presence of other HPV genotypes not covered by the HC2 panel or to undetectable HPV in the lesion; both these rare occurrences were already described in large cancer series and partially explain the occurrence of HPV-negative CIN 3+.

Despite worldwide human papillomavirus (HPV) types distribution showed constant rates of HPV 16/18 in cervical cancers, regional variations have been consistently documented. Very little data is available on HPV genotype prevalence among Italian women with invasive cervical cancer. This study aims to determine the HPV type distribution in cervical specimens obtained from Italian women diagnosed with invasive cervical cancer and referred to the European Institute of Oncology (IEO). Two hundred-sixty eight cervical specimens were obtained from patients diagnosed with invasive cervical cancer referred to the European Institute of Oncology between 1996 and 2006. Following preparation, all cervical samples were sent to laboratories at the International Agency for Research on Cancer (IARC, Lyon, France) for DNA extraction and HPV typing by the multiplex PCR/APEX assay. The study population was divided into four groups from different macro regions: (i) Milan and surrounding area (n=57, 21.3%), (ii) northern Italy (n=81, 30.2%), (iii) central Italy (n=64, 23.9%) and (iv) southern Italy (n=66, 24.6%). The present study is the first at our knowledge that examines a fair number of Italian cervical cancers, about one tenth of all estimated cervical cancer cases occurring yearly, distributed across the whole country. Two-hundred and fifty-one patients (93.7%) resulted HPV DNA positive; of these 201 patients (80.1%) presented a single infection, whereas 50 women (19.9%) presented multiple infection. One hundred and eighty-nine specimens (75.3%) tested positive for either HPV 16 or HPV 18, whereas 62 (24.7%) resulted positive for other high-risk HPV genotypes only. The proportion of HPV 16/18 positive invasive cervical cancers was similar for all the four geographical Italian areas considered. A statistically significant association with younger age and earlier stage was observed for HPV 16/18 related invasive cervical cancers. The results demonstrate that the proportion of HPV 16/18 cervical cancers is fairly constant in all the areas and covers more than 70% of Italian cervical cancer cases. This observation strengthens the decision to start the vaccination programme in all the Italian regions. In addition, the present study provides new and original data on the genotype related differences of the disease that are worth of further investigation.