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Although the lineages of human papillomavirus type 31 (HPV31) variants are recognized, their clinical relevance is unknown. The purpose of our study was to examine risk of cervical intraepithelial neoplasia Grades 2–3 (CIN2/3) by HPV31 variants. Study subjects were women who participated in the atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesion Triage Study and who had HPV31 infections detected at one or more visits. They were followed semi-annually over 2 years for detection of HPV DNA and cervical lesion. HPV31 isolates were characterized by DNA sequencing and assigned into 1 of 3 variant lineages. CIN2/3 was histologically confirmed in 127 (27.0%) of the 470 HPV31-positive women, 83 diagnosed at the first HPV31-positive visit and 44 thereafter. The odds ratio for the association of 2-year cumulative risk of CIN2/3 was 1.7 (95% CI: 1.0–2.9) for infections with A variants and 2.2 (95% CI: 1.2–3.9) for infections with B variants as compared to those with C variants. Among women without CIN2/3 at the first HPV31-positive visit, the risk of subsequent CIN2/3 was 2.2-fold greater for those with A variants (95% CI: 1.0–4.8) and 2.0-fold greater for those with B variants (95% CI: 0.9–4.9) as compared to those with C variants. Similar associations were observed when CIN3 was used as the endpoint. The findings from our study help to tag HPV31 variants that differ in risk of CIN2/3 and to explain in part why some HPV31 infections regress spontaneously and others lead to disease progression.