PARIS — In an April press release, the Strategic Advisory Group of Experts on Immunization (SAGE) of the World Health Organization (WHO) reported the findings of their review concerning the efficacy of various dose schedules for human papillomavirus (HPV). “A single-dose HPV vaccine delivers solid protection against HPV, the virus that causes cervical cancer, that is comparable to 2-dose schedules,” according to SAGE.
This statement comes on the heels of an article published in the November 2021 issue of Lancet Oncology about a study in India. It found that a single dose of the vaccine provides similar protection against persistent infection from HPV 16 and 18 to that provided by two or three doses.
Will this new information lead French authorities to change their recommendations? What do French specialists think? At the 45th Congress of the French Society for Colposcopy and Cervical and Vaginal Diseases (SFCPCV), Geoffroy Canlorbe, MD, PhD, of the department of gynecologic and breast surgery and oncology, Pitié-Salpêtrière Hospital, Paris, shared his thoughts.
With respect to the Indian study, Canlorbe pointed out that while its findings would need “to be confirmed by other studies,” they were, nonetheless, “excellent news for developing countries where there are challenges when it comes to access to vaccination.”
India and France
During the congress press conference, he went on to say that, at this stage, the findings “cannot be extrapolated” to France. This is because the country’s situation is different. HPV vaccination coverage is low; estimates put it at 23.7%, placing the country 28th out of 31 in Europe.
“This poor coverage has nothing to do with healthcare-related logistical or organizational issues; instead, it has to do with people’s mistrust when it comes to vaccination. Here, people who get the first dose get the subsequent ones,” said Canlorbe. “The very fact of getting two to three doses allows the person’s body to increase the production of antibodies and get a longer-lasting response to the vaccine.”
In addition, he drew attention to several limitations of the Indian study. Initially, the team had planned to enroll 20,000 participants. In the end, there were around 17,000, and these were allocated to three cohorts: single-dose, two-dose, and three-dose. Furthermore, the primary objective, which had initially been focused on precancerous and cancerous lesions, was revised. The new aim was to compare vaccine efficacy of single dose to that of three and two doses in protecting against persistent HPV 16 and 18 infection at 10 years postvaccination. In about 90% of cases, the HPV infection went away spontaneously in 2 years without inducing lesions. Finally, the participants were women in India; therefore, the results cannot necessarily be generalized to the French population.
“This information has to be confirmed. However, as far as I know, there are no new studies going on at the moment. The Indian study, on the other hand, is still in progress,” said Canlorbe.
“In France, I think that for the time being we should stick to the studies that are currently available, which have demonstrated the efficacy and safety of two or three doses,” he concluded. In support of this approach, he cited a recent study on the effects of the national HPV vaccination program in England; there, the vaccination coverage is 80%.
This program was associated with a 95% risk reduction for precancerous lesions and an 87% reduction in the number of cancers, confirming the good results already achieved by Sweden and Australia.
In his comments on the WHO’s stance (which differs from that of the French experts), Jean-Luc Mergui, MD, gynecologist in the department of colposcopy and hysteroscopy at Pitié-Salpêtrière, and former president of the SFCPCV, offered an eloquent comparison: “The WHO also recommends 6 months of breastfeeding as a method of contraception, but this isn’t what’s recommended in France, for the risk of getting pregnant nevertheless remains.”
Indian Study Highlights
Partha Basu, MD, PhD, of the International Agency for Research on Cancer (IARC) in Lyon, France, and colleagues compared vaccine efficacy of a single dose of Gardasil (HPV 9-valent vaccine, recombinant) to that of two and three doses in protecting against persistent HPV 16 and HPV 18 infection at 10 years postvaccination.
According to the protocol, the plan was to recruit 20,000 unmarried girls, aged 10-18 years, from across India. Recruitment was initiated in September 2009. However, in response to seven unexplained deaths reported in another ongoing HPV vaccination demonstration program in the country, the Indian government issued a notification in April 2010 to stop further recruitment and HPV vaccination in all clinical trials. At this point, Basu and his team had recruited 17,729 eligible girls.
After suspension of recruitment and vaccination, their randomized trial was converted to a longitudinal, prospective, cohort study by default.
Vaccinated participants were followed up over a median duration of 9 years. In all, 4348 participants had three doses, 4980 had two doses (at 0 and 6 months), and 4949 had a single dose. Cervical specimens were collected from participants 18 months after marriage or 6 months after first childbirth, whichever was earlier, to assess incident and persistent HPV infections. Participants were invited to an annual cervical cancer screening once they reached age 25 years and were married.
A single dose of HPV vaccine provides similar protection against persistent infection from HPV 16 and HPV 18, the genotypes responsible for nearly 70% of cervical cancers, compared with that provided by two or three doses. Vaccine efficacy against persistent HPV 16 and 18 infection among participants evaluable for the endpoint was 95.4% (95% CI, 85.0 – 99.9) in the single-dose default cohort (2135 women assessed), 93.1% (95% CI, 77.3 – 99.8) in the two-dose cohort (1452 women assessed), and 93.3% (95% CI, 77.5 – 99.7) in three-dose recipients (1460 women assessed).
Canlorbe reported no relevant financial relationships regarding the content of this article.
This article was translated from the Medscape French edition.