Long‐term human papillomavirus genotype‐specific risk of cervical high‐grade intraepithelial lesion and cancer—By age group and triage cytology

Abstract

Human papillomavirus (HPV) genotypes possess different cervical high‐grade intraepithelial lesion and cancer (CIN2+) risks. HPV genotyping is a promising method to increase the specificity of primary HPV screening, but the optimal management of the infections with different genotypes has not been established. We aimed to assess long‐term HPV genotype‐specific CIN2+ risks, stratified by age and triage cytology result in a population‐based cervical cancer screening program. This is a prospective study of 5253 HPV‐positive individuals from the Finnish randomized HPV screening trial, with up to 18 years of follow‐up. HPV‐positive samples were genotyped using Luminex and BD Onclarity assays. The genotyping data were linked to data from four different nationwide health registries. The primary outcome was HPV genotype‐specific cumulative incidence of CIN2+. The CIN2+ cumulative incidence was the highest for HPV16 (38.1%), followed by HPV33/58 (25.4%) and HPV31 (22.2%). The lowest incidences were observed for HPV56/59/66 (4.4%), HPV35/39/68 (6.5%), and HPV51 (7.5%). Individuals aged 50 or older at the entry test had lower cumulative incidences for the highest‐risk genotypes. The cytology stratification showed that for the infections with the highest risks, normal cytology triage did not guarantee a low CIN2+ risk. On the other hand, HPV51 and HPV56/59/66 had a low risk even with an abnormal cytology result. The findings suggest that individuals with HPV16, HPV33/58, and HPV31 infections could be referred immediately to colposcopy. Sending individuals with low‐risk genotypes, HPV35/39/68, HPV51, or HPV56/59/66 infections with normal cytology back to routine screening could increase screening specificity.