Catch-up quadrivalent human papillomavirus (HPV) vaccination with 3 doses was effective against the risk for cervical intraepithelial neoplasia (CIN)2+ and CIN3+ in girls and women age 14 to 20 years at time of first vaccine dose but not for women age 21 and older at first dose, according to a study recently published in The Lancet Child & Adolescent Health.

Available HPV vaccines can provide substantial potential protection against cervical neoplasia. Further, evidence suggests that vaccination has population effectiveness, which includes reduced prevalence of abnormal cervical cytology or HPV vaccine-type specific infections. In the United States, HPV vaccination is recommended for girls age 11 and 12 years, with catch-up vaccination for girls and women age 13 to 26 years. However, the actual vaccine effect has yet to be fully observed, as girls vaccinated in early adolescence have only recently reached the recommended age for cervical screening for HPV and cancer. However, vaccine efficacy can be evaluated in girls and women who initiated the vaccine series at older ages. Therefore, this population-based, case-control study sought to assess the risk for CIN2, CIN3, adenocarcinoma in situ, or cancer (CIN2+ and CIN3+) by prior HPV vaccination status, age at first dose, and number of doses in women participating in a screening program within a large integrated healthcare system.

A total of 4357 incident CIN2+ girls and women and 21,773 matched controls were included. Of these, 1849 were incident CIN3+ girls and women with 9242 matched controls. For each case girl or woman, 5 controls were randomly selected. Cases and controls were age 26 years or younger when the HPV quadrivalent vaccine became available in 2006. Rate ratios (RR) from conditional logistic regression were estimated by an age range at time of first HPV quadrivalent vaccine dose (14-17, 18-20, and ≥21), and number of doses (1, 2, 3 or more doses) compared with no prior vaccination, with adjustment for smoking, hormonal contraceptive prescription, race or ethnicity, sexually transmitted infections, immunosuppression, parity, and number of outpatient visits.

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One or more HPV vaccine doses provided protection against CIN2+ (unadjusted RR, .86; 95% CI, .77-.96) and CIN3+ (unadjusted RR, .82; 95% CI, .68-1.00). The strongest protection against CIN2+ in women who received at least 3 vaccine doses and received their first dose age 14 to 17 (unadjusted RR, .62; 95% CI, .46-.83) or age 18 to 20 (unadjusted RR, .76; 95% CI, .61-.94). Results showed no significant protection was found in women age 21 or older at time of first dose (unadjusted RR, .95; 95% CI, .78-1.17). Inferences were similar for CIN3+, but with stronger effects for women who received at least 3 vaccine doses and received their first dose age 14 to 17 (RR, .29; 95% CI, .14-.60) or age 18 to 20 (RR, .67; 95% CI, .41-1.10). However, no significant effectiveness was found in women who had the first dose of vaccine at age 21 to 26, or in women who received fewer than the full 3 doses.

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Overall, the investigators concluded that, “Consistent with some, but not all studies, our findings do not support catch-up vaccination of women age 21-26 years.” 


Silverberg MJ, Leyden WA, Lam JO, et al. Effectiveness of catch-up human papillomavirus vaccination on incident cervical neoplasia in a US health-care setting: a population-based case-control study. [published online August 7, 2018] Lancet Child Adolesc Health. doi: 10.1016/S2352-4642(18)30220-7