Human papillomavirus (HPV) genotypes in women with cervical precancer and cancer at Kaiser Permanente Northern California

Background: 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. Methods: 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. Results: 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). Conclusions: 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. Impact: 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.