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

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.