Extended HPV Genotyping for Risk Assessment of Cervical Intraepithelial Neoplasia Grade 2/3 or Worse in a Cohort Study

Abstract

Background: We sought to identify the absolute risk of specific HPV genotype for cervical intraepithelial neoplasia grade 2/3 or worse (CIN2+/3+) and to develop a risk-based management strategy in an HPV-positive population. Methods: HPV genotyping was performed based on a 3-year cervical cancer screening cohort. The study endpoints were histologic CIN2+/3+. The prevalence of specific HPV genotype was calculated by minimum, any type, and hierarchical attribution estimate. The absolute CIN2+/3+ risks of specific HPV genotype were estimated and risk-based management strategy was established according to the American Society for Colposcopy and Cervical Pathology guideline. The efficacy of conventional and risk-based management strategies for non-16/18 HPVs were further evaluated. Results: Eligible data were available for 8,370 women with a median age of 48 years (interquartile range, 42–53 years). At baseline, there were 1,062 women with HPV-positive disease, including 424 with multiple and 639 with single infections. CIN2+/3+ cases represented 113/74, 23/8, 20/7, and 52/31 patients at baseline and first-, second-, and third-year visits, respectively. Women with multiple HPV infections at baseline were more prone to persistent infection than those with single infection (P<.0001). HPV16 and HPV52 were the top 2 ranking among baseline and 3-year cumulative CIN2+/3+ cases. Based on the absolute risk of specific HPV genotype combined with cytology for CIN2+/3+, all non-16/18 HPVs were divided into 4 risk-stratified groups. Compared with conventional strategy, the risk-based strategy had higher specificity (P=.0000) and positive predictive value (P=.0322) to detect CIN3+ and needed fewer colposcopies for each CIN3+ case. Conclusions: Based on our study findings, we propose a new extended HPV genotyping protocol, which would provide a better strategy for achieving precise risk-based management of HPV-positive populations.

Clinical evaluation of primary human papillomavirus (HPV) testing with extended HPV genotyping triage for cervical cancer screening: A pooled analysis of individual patient data from nine population‐based cervical cancer screening studies from China

“… 32 , 33 Previous studies have investigated the HPV genotype distribution among Chinese women but most were based on a single center or healthcare institutions, limiting their ability to provide representation of general population. 9 , 29 , 34 , 35 , 36 , 37 , 38 In this study, we used pooled data from nine population‐based cervical cancer screening studies from six parts of China and identified that the five most frequently detected genotypes were HPV52, 16, 58, 68, and 51. We further evaluated HPV genotype distribution stratified by pathology grade as a proxy for risk assessment to identify genotypes that warrant distinct management.…”

“…It has been established that HPV genotype distribution varied greatly by geographic region, with HPV‐16 retaining the most common type globally but HPV52 and 58 being more prevalent in Eastern Asia 32,33 . Previous studies have investigated the HPV genotype distribution among Chinese women but most were based on a single center or healthcare institutions, limiting their ability to provide representation of general population 9,29,34–38 . In this study, we used pooled data from nine population‐based cervical cancer screening studies from six parts of China and identified that the five most frequently detected genotypes were HPV52, 16, 58, 68, and 51.…”

“…32,33 Previous studies have investigated the HPV genotype distribution among Chinese women but most were based on a single center or healthcare institutions, limiting their ability to provide representation of general population. 9,29,[34][35][36][37][38] In this study, we used pooled data from nine F I G U R E 2 HPV genotype distribution among all women (A) and stratified by pathology grade (B) for women with normal histology, (C) for women with CIN1, (D) for women with CIN2, and (E) for women with CIN3+. CIN1, cervical intraepithelial neoplasia grade 1; CIN2, cervical intraepithelial neoplasia grade 2; CIN3+, cervical intraepithelial neoplasia grade 3 or higher; HPV, human papillomavirus.…”

“…We calculated the posttest risks based on the average prevalence of cervical precancers in strata by different combinations of the assessed testing results. 28 We plotted posttest risks against internal benchmark levels derived from the current Chinese management guidelines 29 : the risk of precancers in HPV‐positive women with ASC‐US in the observed population (2.24%) was the threshold for referral to colposcopy; the risk of precancers in HPV‐positive women and negative for intraepithelial lesion or malignancy (NILM, 0.54%) was the threshold for 1‐year return.…”

Distribución de genotipos de virus papiloma humano de alto riesgo en mujeres y hombres atendidos en una red asistencial privada en la Región Metropolitana, Chile

“…Una revisión sistemática de 236 fuentes identificadas con 76 artículos completos recuperados publicada en el año 2020 32 muestra evidencia que respalda la utilidad clínica de caracterizar otros genotipos de VPH-AR, además de los 16 y 18, lo cual podría ser costo-efectivo 32 . En un estudio de cohortes, de Li, X y cols., en 2022 35 , se concluyó que la estrategia de manejo basada en el riesgo…”