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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.)

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+.

Objective: Recent data showed that HPV16 infections in young women can lead to CIN3 formation very quickly and questioned the common assumption that invasive cervical cancer develops through slowly progressing pre-cancer lesions, CIN1, CIN2 and CIN3. The aim of the study is to compare the age distribution of HPV 16/18 related and HPV16/18 not related CIN., Methods: We used the data generated from the clinical use of HPV genotyping (LINEAR ARRAY, Roche Diagnostics). Patients were grouped on the basis of histology, CIN1 vs. CIN2+ and on HR-HPV genotype status., Results: The probability to develop a CIN2+ seemed to decrease with age in patients infected with HR-HPV genotype 16/18 while the inverse effect was observed in CIN2+ patients who were HR-HPV positive but HPV16/18 negative (Chi-square test, p(trend)=0.01). Only in HR-HPV positive but HPV 16/18 negative patients, a relative reduction of CIN1 vs. CIN2+ was observed with increasing age (Cochran-Armitage test, p(trend)=0.01); finally, in HR-HPV non-16/18 infected patients only a statistically significant difference in mean age between CIN1 and CIN2+ patients below age 35 was observed., Conclusions: Besides the limitations of the present cross-sectional analysis, these data suggest a genotype specific natural history of cervical cancer precursors development: one type, more frequent, HPV16/18 related, which develops quick and early in life; another one, non-16/18 HR-HPV related, which develops later, slowly, through low- to high-grade lesions. If confirmed, this hypothesis could influence screening policies, especially in the vaccinated population., (Copyright © 2011 Elsevier Inc. All rights reserved.)

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.

Although cervical cytology screening has dramatically reduced its incidence, cervical cancer still occurs. The clinical history of 261 cervical cancer patients referred to the European Institute of Oncology between 1996 and 2006 was analysed in depth to better understand the difficulties in the diagnosis and prevention of this neoplasia in Italy. Data concerning anagraphical characteristics, tumour type and stage, Pap smear history, colposcopic and histologic data, treatment outcome were reviewed. Patients who had taken Pap smear in the 3-year time span preceding diagnosis were 199 and 55 (27.7%) of these smears were negative. A negative Pap smear was observed in 62.5% of the women with a cancer at stage IV or III. One hundred and seventy-two patients were symptomatic at diagnosis: 43 (25%) had a negative Pap smear in the 3 years preceding diagnosis while 54 (31.4%) had never done a Pap smear or had one taken more than 3 years before. Eighty-nine women were asymptomatic at the time of diagnosis; 13 patients (14.6%) had a negative Pap smear while 8 had no smear taken in the 3 years preceding diagnosis or no smear at all. The present retrospective investigation indicates that the screening system still has some critical points. Although multiple techniques and approaches have been proposed to improve the general performance of the system, prophylactic vaccination may dramatically limit the failures in an easier, and possibly more cost-effective way. We also stress that history taking and clinical examination are important tools to diagnose cervical cancers. However a clinical diagnosis requires experience, which, with the advent of more efficient screening system and prophylactic vaccination, many of the newer practising gynaecologists might lack.