As eyes turn to the development of therapeutic mRNA vaccines against cancer, we sometimes forget that there are already vaccines that can prevent certain cancers. In addition to the vaccine against hepatitis B, which helps to prevent liver cancer, that against human papillomavirus (HPV) infections is a particularly effective weapon for preventing HPV-induced cancers, including cancers of the cervix, of the vagina, vulva, penis, anus, as well as cancers of the oropharyngeal sphere (larynx, hypopharynx, oropharynx and oral cavity).
However, in France, HPV vaccination coverage remains low: only 46% of young girls (compared to more than 80% in Norway, Sweden, Iceland, England and Portugal) and 6 to 8% of boys were protected. by a complete vaccination schedule in 2022.
To convince us of the interest in vaccinating adolescents and young adults against HPV, we must understand how these viruses behave and how they are transmitted.
Transmission et contamination
The first thing to say is that HPVs are extremely widespread – eight out of ten people will be confronted with them during their lifetime – and that they constitute a very large family: there are more than 200. Some have what is called a “cutaneous tropism”, that is to say that they infect the cells of the skin and are in particular responsible for skin conditions such as plantar or palmar warts. Others, and these are the ones that particularly interest us here, are said to be “mucosal tropism”, ie they infect the epithelial cells of the genital and oral mucous membranes.
They are transmitted during sexual intercourse by skin-to-skin contact. This means that transmission can take place even if there is no vaginal or anal penetration, during caresses, orogenital intercourse (cunnilingus, fellatio, rimming), but also in the event of sharing sex toys or laundry. Suffice to say that male and female condoms and dental dams are not enough to prevent all the risks of contamination.
Among these mucosal-tropic HPVs, some (HPVs 6 and 11) are said to be “low carcinogenic risk”. Infection with these viruses can cause the appearance of genital warts (condyloma) which, even if they are not responsible for cancer, can be as disabling as they are unsightly and which are often difficult to get rid of. And then there are so-called “high carcinogenic risk” or “oncogenic” HPVs (HPV 16, 18, 31, 33, 45, 52, 58 and in particular HPV 16 and 18) which are likely to cause cancer. .
“Susceptible” because in 90% of cases, when there is an HPV infection, the body manages to get rid of it. But in the remaining 10%, the risk of developing cancer is there. Dr. Hélène Pere, virologist at the European Georges-Pompidou Hospital (AP-HP), explains the mechanism: “If the infection becomes persistent, the virus can transform the cell it infects into a tumor cell. One of the mechanisms of tumor transformation is the integration of the viral genome into the genome of the cell it infects, which results in an over-expression of the viral oncoproteins E6 and E7 at the origin of the transformation of the normal cell into cancer cell.”
She adds that the process from contamination to cancer is long and gradual: “Regarding HPV-induced cervical and anal canal cancers, the process between initial infection and invasive cancer can last more than fifteen years with different stages. Chronic infection can progress to low-grade tumor lesion, then to high-grade tumor lesion and finally to invasive cancer.”
A very effective vaccination, which could be extended
As we said, condoms offer only incomplete protection against HPV. It is vaccination that allows very effective prevention against HPV 6, 11, 16, 18, 31, 33, 45, 52 and 58. Dr. Hélène Péré points out: “It is a vaccine, prophylactic and altruistic that prevents infection and prevents transmission. It is necessary to vaccinate the concerned and the vectors in order to eliminate the pathogen. It is necessary to have a global non-gendered vaccination.” And to specify: “It is advisable to be vaccinated before entering sexual life in order to develop neutralizing antibodies which will prevent the virus from infecting cells at the time of exposure.”
This is the direction of the recommendations in France, where the HPV vaccine is recommended for girls and boys aged 11 to 14 with a two-dose schedule. In addition, catch-up vaccination is possible for young women and young men between the ages of 15 and 19 and for men who have sex with men up to the age of 26, according to a three-dose schedule.
These recommendations could be expanded in the future, as Dr. Hélène Péré points out: “The question arises of extending the catch-up age to young women and young heterosexual men.” In addition, other indications could be added in the future, notes the virologist: “Different countries also recommend the HPV vaccine post-treatment after conization [suppression chirurgicale d’une portion du col de l’utérus, ndlr] high-grade cervical tumor lesions. For this to be considered in France, more robust studies and larger cohorts are needed to ensure that the vaccine does indeed reduce the risk of recurrence after treatment, as has been shown in initial studies carried out on a small number of women.
Also to note: a study is underway to assess the efficacy of the Gardasil 9 vaccine against treatment-resistant warts, even though they are caused by HPVs not covered by the vaccine. “The literature shows that it could work. But to be sure, and because the placebo effect is particularly strong for palmar and plantar warts, we need a randomized, comparative, double-blind trial comparing two parallel groups.” explains Dr. Johan Chanal, dermatologist at Cochin Hospital and coordinating investigator of this trial. To be continued, therefore.
Obstacles to getting vaccinated in France
But for the time being, the objective is above all to increase vaccination coverage among young people and to do this, it is crucial to inform parents but also adolescents, while understanding what has led France to move. HPV vaccine. “Rumours about the adverse effects of this vaccine and the fact that it is associated with sexuality have harmed HPV vaccination in France”notes Dr. Hélène Péré.
Indeed, information had circulated at the time of the placing on the market of Gardasil, suggesting an increase in the cases of autoimmune diseases in vaccinated young girls. “According to WHO and ANSM data, this is absolutely not the case”insists the virologist. “There is no over-representation of any disease where the vaccine is used routinely”abounds Dr. Johan Chanal, who postulates an erroneous judgment insofar as puberty is a period when many autoimmune diseases are diagnosed.
Dr. Hélène Péré raises another obstacle to vaccination in our country: “The weak culture of prevention in France could also play a role.” It is sometimes difficult for some parents to conceive the interest of a vaccine when the risk is not currently present.
In order to improve the vaccination rate among young people, the virologist suggests vaccinating at school as is done in Spain, for example: “Vaccinating systematically at school would make it possible to extend vaccination and therefore increase vaccination coverage in France. By creating group emulation, potentially worried parents could be reassured and this would also make it possible to reach children whose parents are not sufficiently informed.
As far as information is concerned, it can be just as important to reach the first concerned via campaigns immediately aimed at teenagers, as the Arc Foundation recently did via its campaign “The Papilloma Report”.
“Wide vaccination could help get rid of HPV-induced cancers against which the vaccine protects”concludes Dr. Hélène Péré. Every year in Francenearly 3,000 women develop cervical cancer and 1,000 die from it.
