Abstract 2230: Extended human papillomavirus genotyping to predict progression to high-grade cervical precancer: A prospective cohort study in the southeastern United States
Authors: Bukowski Alexandra , Hoyo Cathrine , Hudgens Michael G. , Brewster Wendy R. , Valea Fidel , Bentley Rex C. , Vidal Adriana C. , Maguire Rachel L. , Schmitt John W. , Murphy Susan K. , North Kari E. , Smith Jennifer S. 
Published: June 2022

Abstract
Background: High-risk human papillomavirus (hrHPV) testing is recommended for primary cervical cancer screening and is used alongside cytology to triage screening abnormalities to colposcopy. Most screening-based hrHPV tests involve pooled detection of any hrHPV type or of HPV 16/18 only. Extended HPV genotyping, particularly of non-16/18 hrHPV types, may improve risk stratification for millions of cervical abnormalities detected each year, but HPV genotype-specific progression risks are not well characterized. HPV genotype-specific incidence of high-grade cervical intraepithelial neoplasia or more severe (CIN2+) was examined among individuals with normal or low-grade (CIN1) histology following an abnormal screening cytology result.
Methods: A US-based prospective, multiracial cohort of 343 colposcopy referral patients with normal (n=226) or CIN1 (n=117) histology was assessed. Baseline cervical samples underwent HPV DNA genotyping. Participants were followed for up to five years. Genotype-specific CIN2+ incidence rates (IR) were estimated with accelerated failure time models for interval-censored data. Cumulative CIN2+ risk over five years was estimated non-parametrically and compared for HPV risk groups (HPV 16/31/18, else HPV 33/58/52/45, else HPV 39/68/35/51/59/56/66) and age groups (ages 21-24, 25-29, 30+).
Results: At enrollment, median participant age was 30.1 years; 67.1% were hrHPV-positive. During follow-up (median 24.3 months), 24 participants progressed to CIN2+ (7.0%; 6.2% among normal histology and 8.6% among CIN1). CIN2+ IR among hrHPV-positive participants was 3.2/1,000 person-months. CIN2+ IRs were highest for HPV 16 (IR 8.3; 95% CI 4.1, 16.6), HPV 33 (IR 7.8; 95% CI 2.0, 31.3), and HPV 58 (IR 4.9; 95% CI 1.2, 19.6). IRs were highest for HPV 16, 68, and 33 among normal histology and for HPV 33, 31, 16, and 58 among CIN1. Five-year CIN2+ risks were 0.27 for HPV 16/31/18, 0.11 for HPV 33/58/52/45, and 0.13 for HPV 39/68/35/51/59/56/66 (p=0.04). CIN2+ risk did not differ by age group.
Conclusion: In addition to the established HPV type 16, HPV 33 and 58 were consistently predictive of progression to CIN2+ over a five-year period in this cohort. These findings also support the utility of HPV risk groups to stratify women with non-16/18 hrHPV positivity who exhibit differential risks of progression. Additionally, HPV risk groups appear to predict progression regardless of age; thus, although hrHPV testing is not recommended for initial screening of women under 30 years of age, it may be a risk-stratification tool for these younger women, once a cervical abnormality is found. In conclusion, extended genotyping of non-16/18 hrHPV may be useful to identify individuals with normal or low-grade histology results who are at increased risk of progression to CIN2+, thereby improving the efficacy of cervical cancer screening.
Citation Format: Alexandra Bukowski, Cathrine Hoyo, Michael G. Hudgens, Wendy R. Brewster, Fidel Valea, Rex C. Bentley, Adriana C. Vidal, Rachel L. Maguire, John W. Schmitt, Susan K. Murphy, Kari E. North, Jennifer S. Smith. Extended human papillomavirus genotyping to predict progression to high-grade cervical precancer: A prospective cohort study in the southeastern United States [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2230.