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Prophylactic human papillomavirus vaccines have been shown to be effective in reducing the disease burden of cervical cancer, but the three dose regimen can be expensive and difficult to complete. With that in mind, Dr Aimée R. Kreimer, investigator in the division of cancer epidemiology and genetics at the National Cancer Institute, the National Institute of Health, and colleagues sought to determine if less than three doses of the vaccine would be effective. The results are published in the Journal of the National Cancer Institute.
Prophylactic human papillomavirus vaccines have been shown to be effective in reducing the disease burden of cervical cancer, but the three dose regimen can be expensive and difficult to complete. With that in mind, Dr Aime R. Kreimer, investigator in the division of cancer epidemiology and genetics at the National Cancer Institute, the National Institute of Health, and colleagues sought to determine if less than three doses of the vaccine would be effective. The results are published in the Journal of the National Cancer Institute.
The study leveraged data from a three-dose efficacy study conducted among women between the ages of 18 and 25 in Costa Rica. At enrollment, baseline data were collected and women were randomly assigned in a double blind manner to the intervention group or the control group. Participants in the intervention group received Cervarix while the control group received a hepatitis A vaccine (a modified preparation of Havrix). Women were followed for four years and were seen annually where cervical samples were collected. Although all women were expected to receive three doses of the intervention or control vaccine in the original study, 20% of the original 7,466 participants received fewer doses mostly due to pregnancy or colposcopy. Thus, the researchers had groups of women who received three doses (N=2,965 for vaccine; N=3,010 for control), two doses (N=422 for vaccine; N=322 for control), or one dose (N=196 for vaccine; N=188 for control).
Kreimer and colleagues found similar results of vaccine efficacy across the dosage groups. Specifically, they found vaccine efficacy against newly detected HPV16 or HPV18 that persisted at least one year was 80.9% (95% confidence interval=71.1%to 87.7%), 84.1% (CI=50.2% to 96.3%), and 100% (CI=66.5% to 100%) for three, two and one doses, respectively. Further analysis showed that two doses were more than two-thirds as effective as the full three doses. Kreimer et al. commented, “Our clinical efficacy data provide suggestive evidence that an HPV vaccine program that provides fewer doses to more women could potentially reduce cervical cancer incidence more than a standard three-dose program that uses the same total number of doses but in fewer women.”
“The protection afforded by a single dose of vaccine was unexpected because other subunit vaccines typically require boosting following the prime dose to confer long-term protection, although perhaps many of our sexually active participants had been previously exposed to HPV16 or HPV18,” Kreimer and colleagues added. “If randomized studies and cost-effectiveness analyses confirm the net benefits of administering fewer doses, and the duration of protection is sufficient, then the need for fewer doses may make primary prevention of cervical cancer a reality, especially for women in areas where most cervical cancers occur.”
In an accompanying editorial, Dr Cosette Marie Wheeler, department of pathology and department of obstetrics and gynecology and director of the House of Prevention Epidemiology (HOPE) Clinic at the University of New Mexico Health Sciences Center, noted the study has great implications for the reducing the global burden of HPV-related cancers. She commented, “The age old adage of less is more may apply to HPV vaccination and if so, the report of Kreimer et al. represents an important step on the road to more effective and sustainable cervical cancer prevention programs.”
Wheeler tempered her optimism with caution, however, considering some of the limitations of the study. “It remains unknown whether these observations will translate, over the long term, to the prevention of disease endpoints such as cervical intraepithelial neoplasia grade 3 and higher (CIN3+) and whether HPV vaccine protection, with fewer than three doses, will be sustainable even for homologous HPV vaccine types 16 and 18,” she wrote. “Additional larger studies that are specifically designed to evaluate the efficacy of one-, two-, and three-dose regimens in young adolescent girls, with long-term follow-up and more stringent endpoints, could prove critical.”
Kreimer AR, Rodriguez AC, Hildesheim A, et al. Proof-of-principle evaluation of the efficacy of fewer than three doses of a bivalent HPV 16/18 vaccine. J Natl Cancer Inst. 2011;103(19):1-8.
Wheeler CM. Less is more: a step in the right direction for human papillomavirus (HPV) vaccine implementation. J Natl Cancer Inst. 2011;103(19):1-2.