Risk detection for high-grade cervical disease using Onclarity HPV extended genotyping in women, ≥21 years of age, with ASC-US or LSIL cytology.

There is growing interest in using human papillomavirus (HPV) genotyping as a risk-based triage approach for women with atypical squamous cells-undetermined significance (ASC-US) and low-grade squamous intraepithelial lesions (LSIL) cytology. This analysis includes 2807 subjects with ASC-US or LSIL cytology, ≥21 years, from the baseline phase of the Onclarity HPV trial. All women were referred to colposcopy/biopsy. Hierarchical-ranked prevalence and risk values, associated with high-grade cervical disease, were calculated based on extended genotyping. HPV 16 carried the highest risk for cervical intraepithelial neoplasia grade 2 or worse (≥CIN2) in both the ASC-US and LSIL populations. Risk of ≥CIN3 and ≥CIN2 associated with the other 13 genotypes varied somewhat for women with ASC-US and LSIL, however, HPV 31, 18, 33/58, 51 and 52 appear to comprise an intermediate risk band. Risk associated with HPV 35/39/68, 45, and 56/59/66, in either cytology population, was relatively low and beneath the benchmark threshold risk for immediate colposcopy. Restricting the analysis to women 21-24 years, ≥25 years, or ≥30 years produced similar results. HPV genotyping identified multiple risk bands for ≥CIN3 and ≥CIN2 in the ≥21 year-old ASC-US and LSIL populations. These results support a 1-year follow-up period to preclude immediate colposcopy for ASC-US or LSIL women positive for the lowest-risk HPV genotypes.

Wright TC Jr ，Stoler MH ，Parvu V ，Yanson K ，Cooper C ，Andrews J ... -  《-》

HPV genotyping for triage of women with abnormal cervical cancer screening results: a multicenter prospective study.

Nakamura Y ，Matsumoto K ，Satoh T ，Nishide K ，Nozue A ，Shimabukuro K ，Endo S ，Nagai K ，Oki A ，Ochi H ，Morishita Y ，Noguchi M ，Yoshikawa H ... -  《-》

The Onclarity Human Papillomavirus Trial: Design, methods, and baseline results.

The baseline phase of the Onclarity trial was conducted to determine the screening performance of the Onclarity human papillomavirus (HPV) assay for detecting cervical cancer and precancer (≥CIN2) during triage of women ≥21 years with ASC-US cytology, as an adjunct test in women ≥30 years with normal cytology and for primary screening (HPV alone) in women ≥25 years. 33,858 women ≥21 years were enrolled during routine clinic visits. All women with abnormal cytology, women ≥25 years that were high-risk HPV positive, and a random subset of women ≥25 years, negative by cytology and for HPV, were referred for colposcopy and cervical biopsy. Verification bias adjustment with 95% confidence intervals was applied. ASC-US prevalence was 5.8%. The overall HPV prevalence was 14.7%; for HPV 16, 18, and the 12 other HPV types it was 2.7%, 0.8%, and 11.2%, respectively. The prevalence of ASC-US and HPV was inversely proportional with age. The verification bias adjusted prevalence of ≥CIN2 and ≥CIN3 was 1.8% and 0.8%, respectively. Overall, five cases of cervical cancer were identified (all were HPV positive). The odds ratios associated with any HPV positive genotype, or with individual genotypes HPV 16, HPV 18, and HPV 31, for ≥CIN3, were statistically significant when compared to negative histology (p < 0.0001 for all). This report provides demographic information, cytology findings, HPV genotype information, and histopathology for participants in the baseline phase of this trial and offers further evidence to support genotype-specific screening for cervical cancer and precancer. Clinical Trial Registry URL:https://clinicaltrials.gov/ct2/show/NCT01944722.

Stoler MH ，Wright TC Jr ，Parvu V ，Vaughan L ，Yanson K ，Eckert K ，Karchmer T ，Kodsi S ，Cooper CK ... -  《-》

[Evaluation of CIN2+ /CIN3+ risk of different HPV subtypes infection combined with abnormal cytology status].

Luo HX ，Du H ，Liu ZH ，Zhang LJ ，Wang C ，Wu RF ... -  《-》

Triage of LSIL/ASC-US with p16/Ki-67 dual staining and human papillomavirus testing: a 2-year prospective study.

To investigate human papillomavirus (HPV) DNA testing and p16/Ki-67 staining for detecting cervical intraepithelial grade 2 or worse (CIN2+) and CIN3 in women referred to colposcopy with minor abnormal cervical cytology low-grade squamous intraepithelial lesions (LSIL) and atypical squamous cells of undermined significance (ASC-US). The clinical performance of both tests was evaluated as stand-alone tests and combined, for detection CIN2+ and CIN3 over 2 years. ThinPrep(®) liquid-based cytology (LBC) specimens were collected from 1349 women with repeat LSIL or ASC-US. HPV DNA was performed using Hybrid Capture. Where adequate material remained (n = 471), p16/Ki-67 overexpression was assessed. Clinical performance for detection of histologically diagnosed CIN2+ and CIN3 was calculated. Approximately 62.2% of the population were positive for HPV DNA, and 30.4% were positive for p16/Ki-67. p16/Ki-67 showed no significant difference in positivity between LSIL and ASC-US referrals (34.3% versus 28.6%; P = 0.189). Women under 30 years had a higher rate of p16/Ki-67 compared to those over 30 years (36.0% versus 26.6%; P = 0.029). Overall HPV DNA testing produced a high sensitivity for detection of CIN3 of 95.8% compared to 79.2% for p16/Ki-67. In contrast, p16/Ki-67 expression offered a higher specificity, 75.2% versus 40.4% for detection of CIN3. Combining p16/Ki-67 with HPV DNA improved the accuracy in distinguishing between CIN3 and <CIN3. The absolute risk of CIN3 increased from 15.6% in women who were HPV DNA positive to 27% in women positive for HPV DNA and p16/Ki-67. Those negative for HPV DNA and p16/Ki-67 had a low risk of 1.2% of CIN3. The addition of p16/Ki-67 to HPV DNA testing leads to a more accurate stratification of CIN in women presenting with minor cytological abnormalities.

White C ，Bakhiet S ，Bates M ，Keegan H ，Pilkington L ，Ruttle C ，Sharp L ，O' Toole S ，Fitzpatrick M ，Flannelly G ，O' Leary JJ ，Martin CM ... -  《-》