Bayesian analysis of baseline risk of CIN2 and ≥CIN3 by HPV genotype in a European referral cohort

Abstract

Whereas HPV16 and HPV18 have been the focus in current risk‐based cervical cancer screening algorithms using HPV genotype information, mounting evidence suggests that oncogenic HPV types such as HPV31, 33, 52 and 58 pose a ≥CIN3 risk equivalent to or greater than that of HPV18, and the combined risk of HPV31 and HPV33 rivals even HPV16 in women above 30 years of age. Here, we evaluate the baseline risk of CIN2 and CIN3 by genotype in a colposcopy referral population from Denmark and Italy. In total, 655 women were enrolled upon a referral to colposcopy after a positive screening sample. All samples were HPV analyzed using Onclarity HPV assay with extended genotyping and combined with the histology outcomes, a Bayesian probability modeling was used to determine the risk per genotype assessed. The combined data for this referral population showed that the ≥CIN2 risk of HPV16 was 69.1%, HPV31 at 63.3%, HPV33/58 at 52.7%, HPV18 at 46.6% and HPV52 at 40.8%. For ≥CIN3, the risks were 44.3%, 38.5%, 36.8%, 30.9% and 16.8% for HPV16, HPV31, HPV18, HPV33/58 and HPV52, respectively, indicating that the baseline risk of disease arising from HPV16 is, not surprisingly, the highest among the oncogenic HPV genotypes. We find that the HPV genotype‐specific ≥CIN2 and ≥CIN3 risk‐patterns are so distinct that, for example, 35/39/68 and 56/59/66 should be considered only for low intensive follow‐up, thereby proposing active use of this information in triage strategies for screening HPV‐positive women.

Clinical and Analytical Performance of the BD Onclarity HPV Assay with SurePath Screening Samples from the Danish Cervical Screening Program Using the VALGENT Framework

“…The clinical importance of these observations is the demonstration of the ability of the Onclarity assay to precisely detect clinically relevant HPV infections at the individual genotype level. This information can be used with advanced screening algorithms where individual follow-up recommendations are issued for women with HPV16 and -18 found in screening samples or, as recently proposed by us (26) and shortly to be adopted in the Danish screening program, where individual screening recommendations are issued for samples positive for HPV16, -18, -31, -33, and -51, which pose an overall higher risk of ՆCIN2 than the remaining hrHPV genotypes (27,28).…”

The role of human papillomavirus genotyping for detecting high-grade intraepithelial neoplasia or cancer in HPV-positive women with normal cytology: a study from a hospital in northeastern China

“…Moreover, it has been shown -by Bayesian probability modeling -that there is the highest risk of HSIL+ in HPV16-positive patients; furthermore, HPV31-and HPV33/58-positive patients have a higher risk of HSIL+ compared to HPV18-positive patients [28]. A European study showed that the most common HPV types in women with HSIL and cervical cancer were HPV16/33/31 (59.9/10.5/9.0%) and HPV16/18/45 (63.3/15.2/5.3%), respectively [29].…”

Clinical validation of full genotyping CLART® HPV4S assay on SurePath and ThinPrep collected screening samples according to the International Guidelines for Human Papillomavirus Test Requirements for Cervical Screening

“…HPV16 confers the largest risk in women below 30 years of age (26), whereas HPV16 in combination with 18, 31 and 33 together constitute the highest relative risk of disease in women above 30 years of age (26)(27)(28)(29). Data on the absolute risk of CIN by individual HPV genotypes and the fast evolution of cervical screening technology makes it increasingly relevant to consider HPV type specific risk-based screening algorithms (19,30). From a guideline perspective, risk stratification based on HPV16 and HPV18 is already incorporated into a number of national guidelines for triage of HPV positive screening samples (31), as standalone referral indication for colposcopy or as part of a combined outcome with cytology findings of atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesion (LSIL) in certain settings (28,30,32,33 Here, we assessed the clinical performance of the CLART4S assay relative to that of the comparator assay MGP-PCR (Modified General Primers GP5+/6+ with genotyping using Luminex (BioRad) assay) using the international guidelines for primary cervical cancer screening (4).…”