Alternative dosage schedules with HPV virus-like particle vaccines

Abstract

HPV vaccines can prevent multiple cancers in women and men. Difficulties in the cost and completion of the three-dose vaccine series have led to considerations of alternative dose schedules. In clinical trials, three doses given within a 12-month period versus the standard 6-month period yielded comparable results, and immunogenicity appears comparable with two doses in adolescent females compared to the three-dose series in adult females. While the data are generally supportive of moving to a two-dose vaccine schedule among young female adolescents, the adoption of a two-dose vaccine schedule still poses a potential risk to the strength and longevity of the immune response. Public health authorities implementing a two-dose vaccine schedule should devise risk management strategies to minimize the potential impact on cancer prevention.

Keywords::

• dose schedule
• dosing
• HPV vaccination
• immunogenicity
• virus-like particle

Financial & competing interests disclosure

MA Stanley serves as an advisor to Merck and GSK. AR Giuliano is on Merck advisory and scientific boards and her institution receives grant funding for ongoing clinical trials and investigator-initiated research. S.L.S. is supported by the National Cancer Institute at the National Institutes of Health (Cancer Prevention Fellowship R25T CA147832). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• The cost of HPV vaccines and the difficulty in reaching adolescents with a three-dose series have led to strong interest in modifying the dosing schedule of HPV vaccines by allowing a more liberal schedule over 12 versus 6 months and/or by reducing the number of doses.

• Alternative dose schedules of HPV vaccines are comparable to the standard three-dose series over 6 months.

• Several clinical trials have shown that a two-dose vaccine schedule delivered at 0 and 6 months among young adolescents is equivalent to a three-dose schedule delivered at 0, 1/2 and 6 months among 16–26-year-old females with respect to immunogenicity.

• Long-term duration of immunogenicity following a two- versus three-dose vaccine schedule has not been assessed beyond 3 years post-dose two.

• Clinical efficacy of a two- versus three-dose HPV vaccine schedule has not been evaluated.

• A two-dose HPV vaccine schedule has not been evaluated in males or among those at high risk of HPV-related disease (e.g., men who have sex with men, HIV-positive individuals).

• Some countries have licensed a two-dose HPV vaccine regimen among girls aged 9–14 years. WHO Strategic Advisory Group of Experts provides guidance for a two-dose vaccine schedule in females under 15 years of age.

• Countries need to make in-depth assessments of the risks and devise risk management strategies for worst-case scenarios to minimize impact on cancer prevention strategies and other immunization programs if a two-dose HPV vaccine schedule is implemented.