As of December 2019, 124 countries and territories implemented national HPV vaccination programs. In Sweden, this vaccination was approved in 2006, with the quadrivalent vaccine having been used almost exclusively against HPV types 6, 11, 16 and 18.
Previous studies of HPV vaccines, including randomized trials evaluating efficacy or effectiveness, have shown that these vaccines protect against HPV infection, genital warts, and high-grade precancerous cervical lesions (grade ≥ cervical intraepithelial neoplasia). 2 [CIN2 +] and grade ≥3 [CIN3 +]).
Other studies showed the effectiveness of the HPV vaccine in preventing HPV-related cancers, although the number of cancers was small (10 cases), and the cancer types were not limited to those of the cervix.
Randomized controlled trials cannot easily evaluate the effectiveness of the vaccine against invasive cervical cancer due to the long latency time (time from HPV infection to clinical detection of cervical cancer) and the low risk of cervical lesions after of vaccination.
| Methods |
Between 2006 and 2017, a population of 1,672,983 girls and women aged 10 to 30 years was followed using demographic and health records from across Sweden. We evaluated the association between HPV vaccination and the risk of invasive cervical cancer.
During follow-up, controls were made for age, calendar year, county of residence, and parental characteristics, including education, household income, mother’s country of birth, and her history of illness.
| Results |
During the study period, girls and women were screened for cervical cancer until their 31st birthday. Cervical cancer was diagnosed in 19 women who had received the quadrivalent HPV vaccine and in 538 women who had received the quadrivalent HPV vaccine. They had not received the vaccine.
The cumulative incidence of cervical cancer was 47 cases/100,000 people among women who had been vaccinated and 94 cases/100,000 people among those who had not been vaccinated. After adjustment for age at follow-up, the incidence rate ratio for comparison between the vaccinated and unvaccinated population was 0.51.
After additional adjustment for other covariates, the incidence rate was 0.37. After adjustment for all covariates, the incidence rate ratio was 0.12 among women vaccinated before age 17 years and 0.47 among women vaccinated between ages 17 and 30 years.
| Comments |
In this population-based cohort study, quadrivalent HPV vaccination was found to be associated with a substantially lower risk of cervical cancer. When the analysis was stratified by age at vaccination, the reduction in the incidence of invasive cervical cancer was more pronounced in women who were vaccinated at a younger age.
Although the efficacy and effectiveness of the vaccine against HPV infection, genital warts and high-grade cervical lesions (CIN2 + and CIN3 +) has been established, the results obtained expand the known concepts, by showing that the quadrivalent vaccine against HPV is also associated with a substantially reduced risk of cervical cancer, which is the ultimate intent of HPV vaccination programs.
The greater risk reduction associated with vaccination at a younger age is consistent with previous findings showing a lower risk of genital warts and high-grade cervical lesions. The results of this study also support the recommendation to administer the quadrivalent HPV vaccine before exposure to HPV infection, to achieve a more substantial benefit, since vaccination has no therapeutic effect against preexisting HPV infection.
The authors state that their findings are consistent with data from limited trials and with data from a previous ecological study. A study involving passive monitoring of participants in HPV vaccine trials, using the Finnish cancer registry, did not show any HPV-related cancers in vaccinated women, but there were 10 cases of HPV-related invasive carcinomas in unvaccinated women (including 8 cases of cervical cancer), which corresponds to 100% vaccine efficacy.
A US study showed a significantly lower incidence of cervical cancer in girls and women aged 15 to 34 years during the post-vaccination period than during the revaccination period.
In the words of the authors: “We found that the risk of cervical cancer among participants who had started vaccination before age 17 was 88% lower than among those who had never been vaccinated.
The relative risk indicated that the plausible risk was 66 to 100% less with vaccination. The overall percentage of cervical cancer cases caused by HPV types 16 and 18 is almost 70% worldwide, but the distribution of HPV types may be different among younger women than among older women. .”
The researchers performed a new (unpublished) analysis of the results obtained earlier, in which they did HPV genotyping of 2,850 cancerous cervical tumors; The analysis showed that 84.4% of invasive cervical cancers diagnosed in people ≤30 years of age were associated with HPV types 16 or 18. It is also possible that vaccination results in cross-protection against other types of HPV.
Unvaccinated people would indirectly benefit from HPV vaccination if vaccination coverage of girls and women in a population exceeds 50%. A herd effect of HPV vaccination against genital warts has previously been observed in the Swedish population. However, in this study, the authors did not find this herd effect.
| Limitations of the study |
In the analysis, a small proportion of vaccinated women were misclassified as unvaccinated. However, the authors state, misclassification would be expected to produce a bias towards the null.
Of potentially greater concern is the possibility that the relationship of HPV vaccination and cervical cancer risk was confounded by other factors; in particular, HPV-vaccinated women may have been generally healthier than unvaccinated women.
The authors adjusted for several parental characteristics that could be associated with vaccination uptake and underlying cervical cancer risk, and confounding by lifestyle and health factors in women (smoking, sexual activity, drug use). oral contraceptives, obesity) cannot be excluded. These factors are known to be associated with a risk of cervical cancer, although their independent association with HPV vaccine uptake is inconclusive.
Adjusting for parental education level and annual family income may have served to some extent as a proxy for lifestyle factors such as smoking. While healthy volunteer bias would be expected to be more prominent among women who had paid for opportunistic vaccinations (a population that almost exclusively received vaccination after age 17), the researchers found greater risk reductions among women who were vaccinated before the age of 17.
Furthermore, the higher cervical cancer detection rate among HPV-vaccinated women is expected to increase the probability of detecting asymptomatic cervical cancer, and this could potentially cause an underestimation of the risk reduction.
Because the risk of CIN2+ among HPV-vaccinated women is lower than among unvaccinated women, it is unlikely that differential rates or types of treatment of premalignant cervical lesions between vaccinated and unvaccinated women could result. lead to a lower risk of invasive cervical cancer in the vaccinated population.
Because of the small number of cervical cancer cases observed among vaccinated women, the authors were unable to reliably estimate the association of vaccination with cervical cancer risk, according to the number of vaccine doses.
In this large national study of girls and young women aged 10 to 30 years, who were vaccinated through HPV vaccination programs in Sweden, HPV vaccination was found to be associated with a substantially reduced risk of neck cancer. invasive uterus.
| Conclusions |
Among Swedish girls and women aged 10 to 30 years, vaccination with quadrivalent HPV vaccine was associated with a substantially reduced risk of invasive cervical cancer, at the population level.
