Human Papillomavirus (HPV) Genotypes in Women with Cervical Precancer and Cancer at Kaiser Permanente Northern California

Abstract

The human papillomavirus (HPV) Persistence and Progression Cohort is a natural history study of carcinogenic HPV positive women. Here, we present the HPV genotypes found in first ∼500 cases of cervical intraepithelial neoplasia grade 3 (CIN3) or more severe disease (CIN3+) diagnosed at the study baseline. Women aged 30 and older were screened for cervical cancer using Pap smears and tested for carcinogenic HPV using Hybrid Capture 2 (HC2; Qiagen). We randomly selected women who tested HPV positive and were diagnosed with CIN3+ (n = 448) or without CIN3+ (<CIN3; n = 830). Residual cervical Pap specimens were HPV genotyped using a MY09/11 L1-targeted PCR method. Among HC2-positive women, HPV16 (48.9%), HPV31 (9.2%), and HPV18 (8.5%) were the most common HPV genotypes in CIN3+. There was a decrease at older ages in the fraction of CIN3 (P(trend) = 0.006), adenocarcinoma in situ (AIS) (P(trend) = 0.08), and CIN3/AIS (P(trend) = 0.002) associated with HPV16. Compared to the other carcinogenic HPV genotypes in aggregate, HPV18 was strongly associated with CIN3+ in women with a normal Pap [odds ratio (OR) = 5.7, 95% CI = 1.2-26] but not in women with abnormal Pap (OR = 1.3, 95% CI = 0.74-2.3). HPV16 is more strongly associated with cervical precancer diagnosed in younger women (vs. older women). HPV18 infections were linked to precancerous lesions that were missed by cytology. The progression timeline of HPV16 differs from other carcinogenic HPV genotypes, which may impact the use of HPV16 detection in the management of HPV-positive women.