A single dose of the human papillomavirus vaccine is effective at preventing infections over three years, most likely lowering rates of cervical cancer and other diseases linked to the virus, according to a study in Kenya.
The results of the study are the first confirmation from a gold-standard clinical trial that a single dose may be as effective as two or three doses, at least over three years.
Experts said a single-dose strategy would dramatically extend supplies of the vaccine, lower costs and simplify distribution, making vaccination a more viable option in countries with limited resources.
HPV, a sexually transmitted infection, is linked to cervical cancer and other malignancies and in many countries, including the US, health officials recommend two doses of the vaccine for adolescent girls under 15, and three doses for those who are older.
But observational data have long suggested that a single dose offers effective protection against HPV for at least a decade, reports The New York Times.
Although the new findings are evidence of this, results of a direct comparison of one- and two-dose regimens will not be available until 2025.
At least 24 countries, including Mexico, Tonga and Guyana, have shifted to the one-dose approach, reports the WHO.
The new evidence, announced last month at the 35th International Papillomavirus Conference in Washington by researchers from the Kenya Medical Research Institute (KEMRI) and Massachusetts General Hospital (MGH), may convince more countries to adopt the strategy.
The WHO estimates that if widely deployed, a single-dose strategy could prevent 60m cervical cancer cases and 45m deaths worldwide over the next 100 years.
Cervical cancer is the fourth most common type of cancer in women worldwide, with an estimated 604 000 new cases in 202O. It killed around 342 000 women in 2020, more than the number who died during pregnancy or childbirth.
More than 95% of cervical cancer is caused by sexually transmitted HPV. Multiple strains of the virus are prevalent, but subtypes 16 and 18 are responsible for 70% of the cancers.
The HPV vaccine debuted in 2006 and is a “near-perfect prevention intervention for cervical cancer and other HPV-associated cancers”, said Dr Ruanne Barnabas, chief of the division of infectious diseases at Massachusetts General Hospital, who led the study.
Since the FDA approved the vaccine that year in the US, infections with the viral strains causing cancers have dropped by more than 80%.
HPV’s toll is much higher in low- and middle-income countries, where women have limited access to screening for cervical cancer or treatments. Roughly 90% of the deaths from cervical cancer in 2020 were among women in resource-poor countries.
In Kenya, the vaccine is currently given in two doses. But only 33% of girls aged nine to 14 receive the first dose, and only 16% return for the second. By contrast, more than 78% of adolescent girls in the US received at least one dose of the vaccine in 2021.
A single-dose vaccination regimen is easier to implement on a large scale and opens up more channels of delivery, such as village-wide campaigns and mobile clinics.
“It allows an opportunity for creativity of the delivery machinery,” said Dr Peter Dull, who leads HPV vaccine development at the Bill & Melinda Gates Foundation, which funded the study.
In the KEN SHE study, researchers randomly assigned 2 275 Kenyan women from 15 to 20 to receive a single dose of the HPV vaccine targeting subtypes 16 and 18; an HPV vaccine targeting 16, 18 and seven other subtypes; or the meningococcal vaccine, as a control.
Cervical and vaginal swabs were collected from the women every six months and scanned for persistent HPV infection up to 36 months.
The vaccine had an efficacy of 98% against the virus subtypes 16 and 18 over three years, and 96% against all cancer-causing strains, the study found. No serious side effects were reported.
Earlier results from the study, published last year, showed that a single dose of both vaccines was highly effective for 18 months.
Based in part on that evidence, last year the WHO changed its recommendation to one or two doses for girls and young women aged nine to 20, and two doses with a six-month interval for women over 21.
Programmes funded by Gavi have so far reached only about one-third of their goal, partly because of a shortage in vaccine supply. Roughly 20m doses were available in 2022, but that number is expected to more than triple by 2025.
Efficacy of Single-Dose Human Papillomavirus Vaccination among Young African Women (Earlier results)
Ruanne Barnabas, Elizabeth Brown, Maricianah Onono, Elizabeth Bukusi, Betty Njoroge, Rachel Winer, Denise Galloway, for the KEN SHE Study Team.
Published in NEJM Evidence on 11 April 2022
Abstract
Background
Single-dose human papillomavirus (HPV) vaccination, if efficacious, would be tremendously advantageous, simplifying implementation and decreasing costs.
Methods
We performed a randomised, multicentre, double-blind, controlled trial of single-dose nonavalent (HPV 16/18/31/33/45/52/58/6/11 infection) or bivalent (HPV 16/18 infection) HPV vaccination compared with meningococcal vaccination among Kenyan women 15 to 20 years of age. Enrolment and 6-monthly cervical swabs and a month 3 vaginal swab were tested for HPV deoxyribonucleic acid (DNA). Enrolment sera were tested for HPV antibodies. The modified intent-to-treat (mITT) cohort comprised participants who had an HPV antibody-negative result at enrolment and an HPV DNA-negative result at enrolment and month 3. The primary outcome was incident persistent vaccine-type HPV infection by month 18.
Results
Between December 2018 and June 2021, 2275 women were randomly assigned and followed. A total of 758 participants received the nonavalent HPV vaccine, 760 received the bivalent HPV vaccine, and 757 received the meningococcal vaccine; retention was 98%. Thirty-eight incident persistent infections were detected in the HPV 16/18 mITT cohort: one each among participants assigned to the bivalent and nonavalent groups and 36 among those assigned to the meningococcal group. Nonavalent vaccine efficacy (VE) was 97.5% (95% confidence interval [CI], 81.7 to 99.7%; P≤0.0001), and bivalent VE was 97.5% (95% CI, 81.6 to 99.7%; P≤0.0001). Thirty-three incident persistent infections were detected in the HPV 16/18/31/33/45/52/58 mITT cohort: four in the nonavalent group and 29 in the meningococcal group. Nonavalent VE for HPV 16/18/31/33/45/52/58 was 88.9% (95% CI, 68.5 to 96.1; P<0.0001). The rate of serious adverse events was 4.5% to 5.2% by group.
Conclusions
Over the 18-month timeframe we studied, single-dose bivalent and nonavalent HPV vaccines were each highly effective in preventing incident persistent oncogenic HPV infection, similar to multidose regimens.
See more from MedicalBrief archives:
Single HPV vaccine dose may be effective against cervical cancer
Meta-analysis finds HPV can help prevent return of cervical cancer
HPV vaccine cuts cervical cancer by nearly 90% — UK population registry study
Australia may be first to eradicate cervical cancer with HPV school vaccinations