Liquid-based cytology and human papillomavirus testing: a pooled analysis using the data from 13 population-based cervical cancer screening studies from China.

The objective of this study was to evaluate the impact of introducing HR-HPV testing in cytology regarding cervical cancer screening practice. A pooled analysis of liquid-based cytology (LBC) and HR-HPV testing using data from 13 population-based cervical cancer screening studies conducted in China was performed. Participants (n=25,404) received LBC and HR-HPV testing. Women found to be positive on screening were referred for colposcopy and biopsy. The effectiveness of screening strategies that use: LBC with HR-HPV triage for atypical squamous cells of undetermined significance (ASC-US), HR-HPV testing with cytology triage for HPV positive tests, or LBC and HPV cotesting was compared with that of LBC screening alone. LBC with HR-HPV triage for ASC-US had similar sensitivity compared with LBC alone, but significantly increased specificity for both cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and CIN3 or worse (CIN3+) endpoints, and had the best balance between sensitivity and specificity among the strategies. LBC and HR-HPV cotesting had the highest sensitivity and negative predictive value (NPV) and could permit a safe extension of screening intervals. Through the use of an immediate colposcopy threshold of ASC-US or worse for HR-HPV positive women and the use of a raised threshold of low-grade squamous intraepithelial lesion (LSIL) or worse for HR-HPV negative women, LBC and HR-HPV cotesting could provide the same effectiveness as LBC testing with HR-HPV triage for ASC-US at baseline tests. The results of the current study support the use of the cervical cancer screening guidelines in China.

Pan QJ ，Hu SY ，Guo HQ ，Zhang WH ，Zhang X ，Chen W ，Cao J ，Jiang Y ，Zhao FH ，Qiao YL ... -  《-》

Pooled analysis of a self-sampling HPV DNA Test as a cervical cancer primary screening method.

Zhao FH ，Lewkowitz AK ，Chen F ，Lin MJ ，Hu SY ，Zhang X ，Pan QJ ，Ma JF ，Niyazi M ，Li CQ ，Li SM ，Smith JS ，Belinson JL ，Qiao YL ，Castle PE ... -  《-》

Human papillomavirus genotype and cycle threshold value from self-samples and risk of high-grade cervical lesions: A post hoc analysis of a modified stepped-wedge implementation feasibility trial.

Human papillomavirus (HPV) testing of self-collected vaginal samples has potential to improve coverage of cervical screening programmes, but current guidelines mostly require those HPV positive on a self-sample to attend for routine screening. A pragmatic modified stepped-wedge implementation feasibility trial was conducted at primary care practices in England. Individuals aged 25 to 64 years who were at least 6 months overdue for cervical screening could provide a self-collected sample. The primary outcomes included the monthly proportion of non-attenders screened, changes in coverage, and uptake within 90 days. Self-samples from 7,739 individuals were analysed using Roche Cobas 4800. Individuals with a positive self-sample were encouraged to attend clinical screening. In this post hoc study of the trial, we related the HPV type (HPV16, HPV18, or other high-risk type) and cycle threshold (Ct) value on the self-sample to the results of clinician-collected sample and cervical intraepithelial neoplasia grade 2 or worse (CIN2+). We wished to triage HPV-positive individuals to immediate colposcopy, clinician sampling, or 12-month recall depending on risk. A total of 1,001 women tested positive through self-samples, and 855 women who had both an HPV-positive self-sample and a subsequent clinician-sample were included in this study. Of these, 71 (8.3%) had CIN2+. Self-sample Ct values were highly predictive of HPV in the clinician sample. Combining HPV type and Ct value allowed stratification into 3 risk groups; 44/855 (5%) were high-risk of whom 43% (19/44, 95% confidence interval [29.7%, 57.8%]) had CIN2+. The majority (52.9%, 452/855) were low-risk, of whom 4% (18/452, 95% CI [2.5%, 6.2%]) had CIN2+. The main limitation of our study was the colposcopy assessment was restricted to individuals who had abnormal cytology after positive results of both self-sample and clinician-collected sample. HPV type and Ct value on HPV-positive self-samples may be used for triage. The difference in the risk of CIN2+ in these groups appears sufficient to justify differential clinical management. A prospective study employing such triage to evaluate laboratory workflow, acceptability, and follow-up procedure and to optimise clinical performance seems warranted. ISRCTN12759467.

Lei J ，Cuschieri K ，Patel H ，Lawrence A ，Deats K ，YouScreen trial team ，Sasieni P ，Lim AWW ... -  《-》

Comparative analysis of HPV testing versus cytology in Danish cervical cancer screening: Insights from a large-scale implementation study.

Human papillomavirus (HPV) testing is the recommended primary screening method against cervical cancer. Denmark started implementing HPV testing as a primary screening method in 2021, but no national data are yet available. We report the results of the first and second screening rounds in a large Danish pilot implementation study. The objective was to compare colposcopy referrals, identify high-grade cervical intraepithelial neoplasia (CIN) and cancer, and positive predictive value (PPV) between HPV-based and cytology-based screening. In the HPV SCREEN DENMARK cohort (established May 2017-December 2019), participants were assigned to HPV-based (n = 28,677) or cytology-based screening (n = 43,622) based on the municipality of residence. The first round of screening showed higher colposcopy referrals in the HPV group (6.4 %) compared to cytology (2.3 %), with HPV screening detecting more CIN3+ (n = 306/28,677 (1.1 %)) than cytology (n = 241/43,622 (0.6 %)) (RR = 1.9 (95 %CI 1.6-2.3). In absolute terms, 41 additional colposcopy referrals resulted in the detection of 10 more cases of CIN2+ and five extra CIN3+ cases per 1000 women screened. The PPV for CIN3+ of a colposcopy initiated by routine screening was similar in the HPV group (24.1 %) and cytology group (25.7 %). Within the initial years of screening, the cumulative incidence of CIN3+ and cervical cancer showed a more rapid increase in the HPV group compared to the cytology group. HPV-based cervical screening detects almost twice as many CIN3+ cases but at the expense of a more than two-fold increase in colposcopy referrals. Furthermore, we found that HPV-based screening detects cervical cancer earlier than cytology-based screening.

Lindquist S ，Kjær SK ，Frederiksen K ，Ørnskov D ，Munk C ，Waldstrøm M ... -  《-》

Effectiveness of high-risk human papillomavirus genotyping for cervical cancer screening. A multicentre screening cohort study in rural China.

Yu YQ ，Jiang MY ，Zhang X ，Pan QJ ，Dang L ，Feng RM ，Ali NM ，Chen W ，Qiao YL ... -  《-》