The need for numerous doses of the HPV vaccine has been called into question by researchers who say that a one-dose schedule could be sufficient and should be investigated for the protection of most women against cervical cancer.
The suggestion comes from the authors of a new analysis to combine data from two large phase 3 trials that has been published in The Lancet Oncology.
Co-lead author Dr. Aimée Kreimer, from the US National Cancer Institute, says there are potential benefits: “If one dose is sufficient, it could reduce vaccination and administration costs as well as improve uptake.”
“This is especially important in less developed regions of the world where more than 80% of cervical cancer cases occur,” she adds.
The authors introduce their findings with information about the burden of cervical cancer – it is a leading cause of women’s deaths from cancer worldwide, disproportionately affecting women in low-income countries.
A number of human papillomavirus (HPV) types account for virtually all cases of cervical cancer. The authors cite that HPV type 16 causes about 50% of cervical cancers, HPV-18 causes about 20%, and 10 other carcinogenic types mostly account for the remaining 30%.
HPV-16 and HPV-18 are targeted by the two commercially available vaccines: Cervarix made by GlaxoSmithKline (GSK) and Gardasil made by Merck.
These are presently given prophylactically via three doses in a “prime-prime-boost” schedule over a 6-month period – but, says Dr. Kreimer:
“Our findings question the number of HPV vaccine doses truly needed to protect the majority of women against cervical cancer, and suggest that a one-dose schedule should be further evaluated.”
The researchers say the new combined analysis of two independent trials strengthens previous findings.
The National Cancer Institute’s Costa Rica HPV Vaccine Trial found that young women experienced equal protection against HPV-16/18 infection for at least 4 years after being vaccinated with one, two or three doses.
The analysis combined data from that trial – involving 7,466 healthy women between 18 and 25 years of age – with results the PATRICIA trial, involving 18,644 healthy women aged 15-25 years.
Both trials had a randomized design for testing the vaccine intervention – women would get the HPV-16/18 vaccine or a control vaccine (for hepatitis A) in three doses at enrollment, at 1 month and at 6 months.
Some of the women, however, received fewer than three doses, mainly because pregnancy meant they stopped their immunization schedule.
High vaccine efficacy in the women, followed for 4 years on average, was seen against HPV-16/18 infections, regardless of the number of doses received:
- Three doses produced 77% efficacy (among over 22,000 women receiving the full schedule)
- Two doses gave 76% efficacy (among over 1,100 women)
- One dose produced 86% effectiveness (out of over 500 women).
Dr. Julia Brotherton, from the Victorian Cytology Service Registries in Melbourne, Australia, says:
“If HPV vaccines could be delivered as one dose, while retaining their efficacy against the most oncogenic HPV types 16 and 18, the global burden of cervical cancer would substantially decrease.”
“Data from studies have shown how effective one-vaccine dose campaigns can be in even the most resource-poor settings (eg., meningitis A vaccines in sub-Saharan Africa),” she adds. “We can imagine that such campaigns could happen every 5-10 years with the aim of vaccination of, for example, all 9- to 14-year-old girls with one dose of the HPV vaccine.”
The authors of the study caution that more data would be needed before policy guidelines could be changed, however.
Dr. Cosette Wheeler, co-lead author from the University of New Mexico Health Sciences Center in Albuquerque, says:
“Using existing data, we showed that a single dose of the bivalent HPV vaccine may be sufficient to substantially reduce cervical cancer incidence. Yet, a new randomized study will be needed to confirm these findings and move the field forward. Additionally, duration of protection from a single dose must be demonstrated beyond 4 years.”