Fewer HPV Vaccine Doses May Still Lower Risk for Condyloma

Maximum reduction in condyloma risk occurred after 3 doses of quadrivalent human papillomavirus (HPV) vaccine, but 2 doses also considerably reduced condyloma risk, according to an open cohort study published in the February 12 issue of JAMA. The findings suggest the need for further study regarding whether a 2-dose vaccine schedule would also protect against cervical cancer.

"Determining vaccine dose-level protection is essential to minimize program costs and increase mass vaccination program feasibility," write Eva Herweijer, MSc, from the Karolinska Institutet in Stockholm, Sweden, and colleagues. "Currently, a 3-dose vaccination schedule is recommended for both the quadrivalent and bivalent [HPV] vaccines. Although the primary goal of HPV vaccination programs is to prevent cervical cancer, condyloma related to HPV types 6 and 11 is also prevented with the quadrivalent vaccine and represents the earliest measurable preventable disease outcome for the HPV vaccine."

HPV vaccine prevents HPV infection, which can cause condylomata (genital warts) and cervical cancer. Although the standard vaccination calls for 3 doses of vaccine, evidence from small clinical trials suggests some efficacy with fewer than 3 doses.

"This is the first study to report on efficacy for fewer than 3 doses of the quadrivalent HPV vaccine," Allan Hildesheim, PhD, chief of the Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics at the National Cancer Institute, Bethesda, Maryland, told Medscape Medical News. Dr. Hildesheim was not involved in the study.

"Its findings are consistent with previous reports suggesting that 2 [doses] and perhaps even a single dose of the bivalent HPV vaccine provides protection against HPV-associated disease," Dr. Hildesheim said.

The goal of this population-based study was to evaluate the association between quadrivalent HPV vaccination and first occurrence of condyloma in relation to vaccine dose, using an open cohort of all females aged from 10 to 24 years living in Sweden (n = 1,045,165). Follow-up occurred between 2006 and 2010 to determine HPV vaccination status and first occurrence of condyloma, according to Swedish nationwide population-based health data registers.

The investigators determined incidence rate ratios (IRRs) and incidence rate differences (IRDs) of condyloma, using Poisson regression with vaccine dose as a time-dependent exposure, with adjustment for current age and parental education and stratification for age when first vaccinated. To account for prevalent infections, they used statistical models including a buffer period of delayed case counting.

2 Vaccine Doses Nearly as Effective as 3 Doses

Of 20,383 incident cases of condyloma identified during follow-up, 322 were in persons who received at least 1 vaccine dose. Receiving 3 doses of vaccine was associated with an IRR of 0.18 (95% confidence interval [CI], 0.15 - 0.22) for condyloma among persons first vaccinated at age 10 to 16 years compared with unvaccinated individuals. In this group, receiving 2 vaccine doses was associated with an IRR of 0.29 (95% CI, 0.21 - 0.40) and with receiving 1 dose with an IRR of 0.31 (95% CI, 0.20 - 0.49).

Compared with no vaccination, the IRD for 1 vaccine dose was 384 cases (95% CI, 305 - 464 cases) per 100,000 person-years; for 2 doses, the IRD was 400 cases (95% CI, 346 - 454 cases), and for 3 doses, the IRD was 459 cases (95% CI, 437 - 482 cases). This yielded the small difference in number of prevented cases between 3 and 2 doses of 59 (95% CI, 2 - 117 cases) per 100,000 person-years.

"Findings from this study, along with those from previous immunogenicity studies of the quadrivalent HPV vaccine and efficacy and immunogenicity of the bivalent vaccine, provide evidence that 3 doses of the HPV [vaccine] might not be required for protection against HPV infection and associated conditions," Dr. Hildesheim said. "Already, some countries have begun to recommend 2 doses rather than 3 doses of the HPV vaccine for prevention of HPV-associated diseases, [and these findings] further suggest benefit from even a single dose of vaccination. These findings have important implications with respect to the feasibility of implementing cost-[effective] and logistically effective HPV vaccination programs in low-resource settings and difficult-to-reach populations."

Limitations of this study include its observational design with the potential for selection bias, possible underestimation from registry data of the true number of condyloma cases, and inability to estimate associations per dose level separately in girls first vaccinated between ages 10 and 13 years.

"An important strength of the present study is its population-based design and the ability to link vaccination status (by number of doses) and condyloma outcomes on an individual level," Dr. Hildesheim said. "The study is limited by the short duration of follow-up, resulting in imprecision of estimates, particularly those for reduced vaccine dosage. The study is also limited by the fact that individuals who opt to receive fewer than 3 vaccine doses of the HPV vaccine might be different from those who receive 3 doses in ways that affect vaccine efficacy estimates (ie, estimates might be biased)."

Dr. Hildesheim recommends future studies to quantify more precisely the benefit of a single dose of the HPV vaccine, as results from 2 observational studies now suggest that a single dose might confer a high degree of protection against HPV and associated diseases.

"This study does not account for HPV disease outcomes other than condyloma," the study authors conclude. "More studies with longer follow-up are needed to assess if these observed reductions in condyloma risk by vaccine dose apply for other HPV-related disease outcomes such as cervical intraepithelial neoplasia and cervical cancer."

The Swedish Foundation for Strategic Research supported this study. Some of the study authors reported various financial disclosures with Merck, Sanofi Pasteur, Merck Sharp Dome, GlaxoSmithKline, and/or the Swedish HPV vaccination registry at the Swedish Institute for Communicable Disease Control, which is currently funded by the Swedish Association of County Councils and the Swedish Institute for Communicable Disease Control. Dr. Hildesheim has disclosed no relevant financial relationships.

JAMA. 2014;311(6):597-603.

Fonte: https://www.medscape.com