Catch-up HPV vaccine most effective when initiated early
Women who receive their first catch-up dose of the human papillomavirus (HPV) vaccination at a younger age may obtain the most benefits in terms of cancer protection, according to a recent study.
“Our findings show that girls and women who did not receive the full vaccine series at age 11–12 [years] can still benefit from significant protection if they receive the full three doses of vaccine by the age of 20. The evidence suggests that protection is strongest the earlier the vaccine is initiated, and after the age of 21, the evidence of effectiveness is unclear,” said study lead author Dr Michael Silverberg from the Division of Research, Kaiser Permanente Northern California, Oakland, California, US.
“These results support existing guidelines recommending the full three-dose HPV vaccination series for girls and women who start the series after their 15th birthday. Additional research is needed to confirm the limited effectiveness of catch-up vaccination for women aged 21–26 years,” said Silverberg and co-authors.
Based on medical records of women enrolled in the Kaiser Permanente Northern California system who had undergone cytology testing between January 1995 and June 2014, researchers identified 4,357 cases of cervical intraepithelial neoplasia (CIN2+ or CIN3+) and compared each case with up to five age-matched controls without cancer (n=21,773). Only women who were eligible for the quadrivalent HPV vaccine (introduced in 2006) were eligible. Ten and 11 percent of the cases and controls, respectively, had received at least one dose of the HPV vaccine.
Compared with women who had not received a dose of the vaccine, the receipt of one or more doses of the HPV vaccine appeared to protect women against CIN2+ (rate ratio [RR], 0.82, 95 percent confidence interval [CI], 0.73–0.93), especially among women who received ≥3 doses and their first dose at a younger age (RR, 0.52, 95 percent CI, 0.36–0.74 and RR, 0.65, 95 percent CI, 0.49–0.88 at age 14–17 years and 18–20 years, respectively at first dose).
The findings were similar in the subset of women with CIN3+ (n=1,849 cases and 9,242 controls), where women who received ≥1 dose of the HPV vaccine were protected against CIN3+ compared with unvaccinated women (RR, 0.77, 95 percent CI, 0.64–0.94), particularly those who received ≥3 doses and at a younger age (RR, 0.27, 95 percent CI, 0.13–0.56 at age 14–17 and RR, 0.59, 95 percent CI, 0.36–0.97 at age 18–20 years at first dose).
Conversely, women who obtained their first dose of the HPV vaccine at age ≥21 years were not protected from CIN2+ (RR, 0.94) or CIN3+ (RR, 0.88), nor were women who received one (RR, 0.84 and RR, 0.90 for CIN2+ and CIN3+, respectively) or two doses only (RR, 0.98 and RR, 0.97 for CIN2+ and CIN3+, respectively) compared with three or more doses of the vaccine (RR, 0.76 and RR, 0.64 for CIN2+ and CIN3+, respectively).
Twenty-three women with CIN3+ had cancer, of whom only three had previously received the HPV vaccine, all of whom received ≥3 doses and were aged ≥21 years at first dose.
Current vaccination practices may still be important
Drs Sarah Dilley and Warner Huh from the University of Alabama, Birmingham, Alabama, US, cautioned that the study did not account for the effect of the HPV vaccine on cervical cancer prevention per se, or on low-grade dysplasia, genital warts, or persistent HPV infection. [Lancet Child Adolesc Health 2018;doi:10.1016/S2352-4642(18)30268-2]
“The results of this study … showed that the HPV vaccine is most effective when given to females at younger ages, but no benefit was found in patients older than 21 years. Efforts towards increasing HPV vaccine uptake should be focused on younger adolescents—with a priority on vaccinating children aged 11–12 years—and providing catch-up dosing for older adolescents,” they said.
“However … the importance of catch-up dosing in young women should not be ignored. Given that prospective efficacy studies have shown benefits for catch-up vaccination up to at least age 26 years, more data is needed before abandoning this practice,” they added.
“[T]he increased HPV type vaccine coverage of the recently introduced nonavalent HPV vaccine is anticipated to prevent more CIN2+ cases than the quadrivalent HPV vaccine is, thus requiring future investigation,” said Silverberg and co-authors.
“Further research in other settings, and using the recently introduced nonavalent vaccine, will now be needed to assess the effectiveness of vaccinating women aged 21-26 years,” said Silverberg.