Effectiveness of 1, 2, and 3 Doses of Human Papillomavirus Vaccine Against High-Grade Cervical Lesions Positive for Human Papillomavirus 16 or 18

Before 2016, human papillomavirus (HPV) vaccination was recommended on a 3-dose schedule. However, many vaccine-eligible US females received fewer than 3 doses, which provided an opportunity to evaluate the real-world vaccine effectiveness (VE) of 1, 2, and 3 doses. We analyzed data on cervical intraepithelial neoplasia (CIN) grades 2-3 and adenocarcinoma in situ (designated CIN2+) from the HPV Vaccine Impact Monitoring Project (HPV-IMPACT; 2008-2014). Archived tissue from CIN2+ lesions was tested for 37 types of HPV. Women were classified by number of doses received >= 24 months before CIN2+ detection. Using a test-negative design, VE was estimated as 1 minus the adjusted odds ratio from a logistic regression model that compared vaccination history for women whose lesions tested positive for HPV-16/18 (vaccine-type cases) with that for women who had all other CIN2+ lesions (controls). Among 3,300 women with available data on CIN2+, typing results, and vaccine history, 1,561 (47%) were HPV-16/18-positive, 136 (4%) received 1 dose of HPV vaccine, 108 (3%) received 2 doses, and 325 (10%) received 3 doses. Adjusted odds ratios for vaccination with 1, 2, and 3 doses were 0.53 (95% confidence interval (CI): 0.37, 0.76; VE = 47%), 0.45 (95% CI: 0.30, 0.69; VE = 55%), and 0.26 (95% CI: 0.20, 0.35; VE = 74%), respectively. We found significant VE against vaccine-type CIN2+ after 3 doses of HPV vaccine and lower but significant VE with 1 or 2 doses.