HPV VACCINE EFFECTIVENESS

The quadrivalent human papillomavirus (HPV) vaccine (Gardasil, Merck) provides significant protection against cervical abnormalities in young women, according to real-world data from Australia, the first country to implement a publicly funded national HPV vaccination program.

Four years into the program, researchers estimate that 3 doses of the vaccine provided 46% protection against high-grade cervical abnormalities and 34% protection against other cervical abnormalities.

Two doses provided 21% protection against both high-grade and other cervical abnormalities, and 1 dose failed to provide any significant protection.

High-grade abnormalities are more likely to develop into cervical cancer than lower-grade abnormalities.

"Given similar sexual behavior and HPV rates, we would expect similar findings in the United States, although effectiveness will also be influenced by coverage of the vaccine in the population," Elizabeth Crowe, MB, from the School of Population Health at the University of Queensland in Brisbane, told Medscape Medical News.

The findings were published online March 4 in BMJ.

Controlled clinical trials have shown the efficacy of the quadrivalent HPV vaccine, but the new data provide much-needed information on the vaccine's effectiveness in a wider population, Crowe and colleagues explain.

In April 2007, Australia became the first country to implement a national HPV vaccination program for girls 12 and 13 years of age. The country also ran a "catch-up" program from 2007 to 2009, offering vaccination to girls 12 to 17 years and women 18 to 26 years. The vaccine is given in 3 doses over 6 months.

Using registry data from Queensland, researchers estimated the effectiveness of the quadrivalent HPV vaccine in 108,353 young women who had their first Pap test from 2007 to 2011.

The cohort consisted of 1062 "high-grade" cases — women whose pap test and follow-up biopsy confirmed a high-grade cervical abnormality; 10,887 "other" cases — women who did not meet the high-grade case definition but had other abnormalities; and 96,404 control subjects — all remaining women, whose pap test results were negative.

In the high-grade group, 11% of women were fully vaccinated, as were 19% of women in the other group and 24% of women in the control group.

The adjusted odds ratio for the 3-dose series (compared with no vaccine) was 0.54 in the high-grade group (95% confidence interval [CI], 0.43 - 0.67) and 0.66 in the other group (95% CI, 0.62 - 0.70), compared with the control group.

"Women with high-grade cervical lesions were significantly less likely than women with normal cytology to have received 3 doses of the quadrivalent HPV vaccine, equivalent to a vaccine effectiveness of 46%," Dr. Crowe reported.

"The vaccine effectiveness among 15- to 19-year-old women was even higher, at 57%. We believe this reflects the fact that HPV16 causes an even higher proportion of high-grade disease in young women because of to its higher oncogenicity and shorter latent period," she explained.

The number needed to vaccinate with 3 doses to prevent 1 cervical abnormality at first screening was 125 for a confirmed high-grade abnormality (95% CI, 97 - 174) and 22 for other abnormalities (95% CI, 19 - 25).

Two doses yielded an adjusted odds ratio of 0.79 for high-grade cases (95% CI, 0.64 - 0.98) and for other cases (95% CI, 0.74 - 0.85).

"Before this study was performed, we did not know whether fewer than 3 doses of vaccine would provide any protection," Dr. Crowe said. "Our findings that 2 doses conferred 21% protection against both high-grade lesions and other lesions are encouraging, but suggest that 3 doses are required for best protection using the current dose schedule."

Implications for Cervical Cancer Screening

The researchers note that "continued observation of this population is necessary to assess the implications for cervical screening recommendations in the coming era of mass vaccination."

For now, cervical screening will remain necessary in vaccinated populations, owing to the relative HPV-type specificity of current vaccines, they point out. However, falling population prevalence of cervical abnormalities "will reduce the sensitivity and positive predictive value of cytological testing, and screening programs will need to adapt to maintain their effectiveness," they say.

"Our data suggest that this task is now becoming more urgent given the relatively rapid impact of the vaccine on disease in the real-world setting. To tackle this, Australia is currently conducting a comprehensive review of cervical screening," the researchers note.

One of the author reports receiving research grants, travel funds, and payments from Merck, GSK, and BioCSL. Another reports being a coinvestigator on Australian HPV epidemiology grants that have received partial unrestricted funding from BioCSL and Merck. The University of Queensland receives royalties from the sale of Gardasil (Merck).

BMJ. Published online March 4, 2014. Abstract