Human papillomavirus test with cytology triage in organized screening for cervical cancer.

In randomized studies, testing for high-risk (HR) human papillomavirus (hrHPV) has been more sensitive than conventional cytology in detecting cervical intraepithelial neoplasia (CIN). The aim of this study was to evaluate the performance of HPV testing in the setting of an organized routine screening program. Since 2012, 35- to 60-year-old women living in the city of Tampere have been screened with the Abbott RealTime hrHPV test. HPV-negative women are referred to the next screening round in five years. HPV-positive women are triaged with conventional cytology, and women with at least low-grade squamous intraepithelial lesion (LSIL+ ) are referred to colposcopy. The remaining HPV-positive women are referred for re-testing after 12 months, and then all HPV-positive women are referred to colposcopy. The data from the last cohort with cytological screening (screened in 2011) is presented for comparison. A total 5637 (70%) women attended the first round of HPV screening, and 369 were HPV-positive. Of them, 54 women LSIL+ were referred to colposcopy, resulting in 16 CIN2+ lesions found. Of the remaining HPV-positive women, 66% were still positive one year later, and were referred to colposcopy, with 18 additional CIN2+ lesions found. The attendance rate to the last round of cytological screening was 71% (5814 women). Sixty-four women with LSIL+ cytology were referred to colposcopy, and 11 CIN2+ lesions were found. Of the 777 women with borderline cytology and scheduled for reflex screening in the following year, 109 (19%) had ASC-US+ , and 57 underwent colposcopy, resulting in six additional CIN2+ lesions found. The total detection rate of CIN2+ was significantly higher in the HPV-screened cohort (6.0/1000 vs. 2.9/1000, p = 0.015). However, the total colposcopy rate was 4% vs. 2%, respectively (p < 0.001). Human papillomavirus testing also seems to be more sensitive than cytology in detecting CIN2+ lesions in the setting of a routine organized screening program, besides in the context of randomized trials. The problem of an increased colposcopy rate needs to be addressed in the future.

Veijalainen O ，Kares S ，Kujala P ，Tirkkonen M ，Vuento R ，Kholová I ，Luukkaala T ，Osuala V ，Mäenpää J ... -  《-》

Primary HPV screening for cervical cancer: Results after two screening rounds in a regional screening program in Finland.

Since 2012, cervical cancer screening has been conducted with a primary high-risk human papillomavirus (hrHPV) test and conventional cytology triage in the city of Tampere, Finland. The women who were screened with the hrHPV test in 2012 were invited to participate in the second screening round in 2017. The aim of the present report was to compare the number of colposcopy referrals and the number of histological high-grade squamous intraepithelial lesion (HSIL)+ (cervical intraepithelial neoplasia [CIN2+]) lesions between the first and second screening rounds of women of a specific age group who were screened twice with the hrHPV test. The primary hrHPV test used was the RealTime hrHPV PCR assay by Abbott. Women with a positive hrHPV test and cytology triage equal to or worse than low-grade squamous intraepithelial lesion or atypical glandular cells, favor neoplasia, were directly referred to colposcopy, whereas hrHPV-positive women with a negative or equivocal cytology triage were re-screened after approximately 12-16 months. hrHPV-negative women were scheduled for re-screening after 5 years. The present report focuses on the cohort of women who were screened twice with the hrHPV test, who were 35-55 years old in 2012, and 40-60 years old in 2017. In all, 8076 women were invited for HPV screening in 2012 and 8331 women were invited for the second round 5 years later, with attendance rates of 70% and 71%, respectively. Of the women who were screened in 2012, 4571 (69%) belonged to the 35- to 55-year age cohort. In 2017, 4807 (73%) of the women aged 40-60 years participated in the screening. In this cohort, 185 (4.0%) colposcopies were performed in the first screening round, compared with 139 (2.9%) in the second round, and the colposcopy rate was 29% smaller in the second round (P = .002). The number of histological HSIL+ cases was 38 (0.8%) during the first screening round and 29 (0.6%) during the second round (P = .220). In the setting of routine organized cervical cancer screening, the initially high colposcopy rate associated with primary HPV screening seems to level off at the second screening round in women who were screened twice with an hrHPV test.

Veijalainen O ，Kares S ，Kotaniemi-Talonen L ，Kujala P ，Vuento R ，Luukkaala T ，Kholová I ，Mäenpää J ... -  《-》

Use of a high-risk human papillomavirus DNA test as the primary test in a cervical cancer screening programme: a population-based cohort study.

To present the results of the first 2 years of a human papillomavirus (HPV) test-based screening programme outside the research context. Population-based cohort study. A cervical service screening programme in Italy. Women aged 25-64 years invited to screening from April 2009 to April 2011. Eligible women were invited to undergo an HPV test: those with a negative HPV test went on to the next screening episode; those with a positive HPV went on to triage with a Pap smear. Women with positive cytology (i.e. positive for atypical squamous cells of undetermined significance or worse, ASC-US+) were referred to colposcopy, whereas those with negative cytology were referred to repeat HPV testing 1 year later. Participation rate, positivity at HPV and at triage, referral rate to colposcopy, positive predictive value for cervical intraepithelial neoplasia grade 2+ (CIN2+) at colposcopy, and detection rate for CIN2+. Participation increased compared with the previous Pap programme (60.6 versus 43.9%). The HPV positivity rate was 7.0; 39.6% of Pap smears were scored as positive, and therefore 2.8% of the women screened were referred for immediate colposcopy. The compliance of women who scored positive for HPV and negative for Pap for repeat HPV testing at 12 months was 78.6%, and the HPV positivity rate was 56.6%. The overall referral rate to colposcopy was 4.6%. The overall detection rate for CIN2+ was 4.5 versus 1.5% of the Pap programme (25-34 years, 8.2%; 35+ years, 3.6%). Compared with the traditional Pap test, the HPV programme recorded a higher response to invitation and an increased DR for CIN2+. The most critical aspects were the reading of cytology in women that were positive for HPV and the increased workload at colposcopy.

Zorzi M ，Del Mistro A ，Farruggio A ，de'Bartolomeis L ，Frayle-Salamanca H ，Baboci L ，Bertazzo A ，Cocco P ，Fedato C ，Gennaro M ，Marchi N ，Penon MG ，Cogo C ，Ferro A ... -  《-》

Prediction of cervical intraepithelial neoplasia grade 2+ (CIN2+) using HPV DNA testing after a diagnosis of atypical squamous cell of undetermined significance (ASC-US) in Catalonia, Spain.

Ibáñez R ，Moreno-Crespi J ，Sardà M ，Autonell J ，Fibla M ，Gutiérrez C ，Lloveras B ，Alejo M ，Català I ，Alameda F ，Casas M ，Bosch FX ，de Sanjosé S ... -  《BMC INFECTIOUS DISEASES》

Three-year longitudinal data on the clinical performance of the Abbott RealTime High Risk HPV test in a cervical cancer screening setting.

Testing cervical smears for the presence of high-risk human papillomaviruses (hrHPV) increases the sensitivity for detecting women with underlying high-grade cervical intraepithelial neoplasia (CIN) and provides better and longer protection against invasive cervical cancer compared to cytology testing alone. The Abbott RealTime High Risk HPV test (RealTime) is a hrHPV DNA test with concurrent partial genotyping for HPV16 and HPV18 and aggregate detection of 12 other hrHPV types that have been extensively analytically and clinically evaluated over the last 6 years. To provide the first 3-year longitudinal data regarding the clinical performance of RealTime, the risk of CIN2+ according to various negative baseline characteristics, and baseline and future risk for CIN2+ at 3 years for women with baseline infection with various hrHPV types were assessed in a cohort of 3,920 Slovenian women that had hrHPV DNA and/or cytology in 36- to 48-month follow-up results after a baseline screening round in 2009/2010. A total of 36 CIN2+ cases were identified in the second screening round. Of these, 17 CIN2+ cases were identified passively through questionnaires/data registries and 19 cases actively as the result of actions triggered by second-round cytology and/or HPV test results. Accumulation of CIN2+ cases during follow-up occurred predominantly in woman with normal cytology at baseline. Among women >30 years old, significantly better protection against CIN2+ at 3 years was associated with a negative hrHPV DNA result at baseline (risk for CIN2+ 0.04% [95 CI, 0.00-0.22%]) than by normal cytology at baseline (risk for CIN2+ 0.68% [95 CI, 0.40-1.08%]). Women with baseline HPV16 infection had a significantly higher risk of CIN2+ at baseline (21.9% [95 CI, 15.2-30.4%]) and baseline plus future risk at 3 years for CIN2+ (33.3% [95 CI, 24.7-44.0%]) in comparison to women with baseline non-HPV16/18 hrHPV infection (7.0% [95 CI, 4.6-10.2%]) or those that were hrHPV-positive (11.7% [95 CI, 9.1-14.9%]). 3-year longitudinal data reinforce evidence from previous studies that RealTime can be safely used in primary HPV-based cervical cancer screening. Concurrent partial genotyping for HPV16/18 should be strongly considered as a triage method for HPV screen-positive women.

Poljak M ，Oštrbenk A ，Seme K ，Šterbenc A ，Jančar N ，Vrtačnik Bokal E ... -  《-》