Despite persistent misinformation and vaccine hesitancy, a new study published in JAMA Oncology has revealed that the human papillomavirus (HPV) vaccine can significantly reduce the risk of precancerous lesions of the vulva and vagina in girls and women.
The study showed that women who received at least one dose of the quadrivalent HPV vaccine had a 37 per cent lower incidence of high-grade vulvovaginal lesions compared with unvaccinated women. The effect was particularly pronounced among those vaccinated between 10 and 16 years of age, who experienced a 57 per cent lower risk compared to their unvaccinated peers.
Considering that cervical cancer continues to be a major health burden worldwide, with 6.6 lakh new cases estimated in 2022 and 94 per cent of the 3.5 lakh deaths occurring in low- and middle-income countries, and that misinformation surrounding the HPV vaccine remains widespread, this study highlights the importance of early vaccination.
The study highlights that HPV vaccination not only protects against cervical cancer but also reduces the likelihood of developing high-grade precancerous lesions later in life, making it highly relevant for public health strategies globally and particularly in countries like India, where cervical cancer remains one of the common causes of cancer-related deaths among women.
What the study found
The Karolinska Institutet study, published in JAMA Oncology, provides robust evidence linking HPV vaccination to a reduced risk of high-grade vulvovaginal lesions. In Sweden, all children in middle school are offered HPV vaccination, which protects against HPV types 6, 11, 16, and 18—viruses that can cause high-grade precancerous lesions and cancers in different parts of the genital area.
The study followed over 7.78 lakh women born between 1985 and 1998 and living in Sweden between 2006 and 2022. Among them, over 2.56 lakh women (32.9 per cent) received at least one dose of the quadrivalent HPV vaccine. Median follow-up durations were 17 years for unvaccinated women, 12.2 years for those vaccinated between ages 10 and 16 years, and 10.8 years for those vaccinated at 17 years or older.
For your daily dose of medical news and updates, visit: HEALTH
During the follow-up period, 98 cases of high-grade vulvovaginal lesions occurred among vaccinated women, compared to 547 cases in unvaccinated women. After adjusting for age, education, income, and maternal medical histories, the fully adjusted incidence rate ratio (IRR) of high-grade vulvovaginal lesions for vaccinated women was 0.63, representing a 37 per cent reduction in risk compared to unvaccinated women.
"In this study, quadrivalent HPV vaccination (i.e., vaccine that protects against four types of HPV) was associated with reduced risk of high-grade vulvovaginal lesions, suggesting that expanding vaccination, especially at younger ages, could help prevent high-grade vulvovaginal lesions," it said.
The protective effect was strongest among women vaccinated at younger ages. For women vaccinated between 10 and 16 years, the IRR was 0.45, corresponding to a 55 per cent reduction in risk. Those vaccinated at 17 years or older had an IRR of 0.80, indicating a reduction in risk that was not statistically significant without applying buffer periods. However, when buffer periods of 1–2 years were applied to account for pre-existing HPV infections, risk reduction became significant even in this older age group.
Women who were born later and had access to subsidised or free HPV vaccination programs had fewer serious precancerous lesions than women who could get vaccinated only through private healthcare. The subsidised group had about a 19 per cent lower risk, while the catch-up group had about a 38 per cent lower risk, suggesting that early vaccination and publicly funded programs offer much better protection.
“Our study is the largest of its kind to investigate the link between HPV vaccination and serious diseases of the vulva and vagina,” said Yunyang Deng, postdoctoral researcher at the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet.
“The results highlight the importance of offering the HPV vaccine to girls at an early stage in life, before they become sexually active.” Jiayao Lei, assistant professor at the same institute, added, “We also want to study the vaccines’ effect on other HPV-related cancers, including in men.”
Consistent with prior research, the study confirms that HPV vaccination significantly reduces the risk of high-grade vulvovaginal lesions.
The study’s results also underline the value of organised vaccination programs. The catch-up and subsidised cohorts, who benefited from higher coverage and earlier vaccination, had lower incidences of high-grade lesions compared to the opportunistic cohort that relied mainly on private healthcare access. This demonstrates that publicly funded, school-based, or national vaccination programs not only increase vaccine coverage but also optimise the timing of vaccination to prevent HPV-related diseases at a population level.
Limitations of the study
Despite its large-scale, population-based design, the study acknowledges several limitations. First, some vaccinated women were misclassified as unvaccinated due to anonymous records in Sweden’s SVEVAC registry. About 8 per cent of doses administered between 2006 and 2015 lacked informed consent records, a factor the researchers say would likely “bias the estimates toward the null,” meaning the true protective effect may be underestimated.
Second, the absence of a dedicated screening programme for vulvovaginal diseases means some lesions may have gone undiagnosed in both vaccinated and unvaccinated groups. The authors point out that any such nondifferential misclassification would again “bias our estimates toward the null.” Additionally, vaccinated women may be more likely to attend screening, which could lead to higher detection rates and therefore an underestimation of the vaccine’s protective effect.
The study also acknowledges challenges in distinguishing cervical from vaginal lesions, noting that “some lesions of cervical origin might be misclassified as vaginal.” Further, the HPV status of the lesions was unavailable. While not all vulvovaginal cancers are HPV-related, the authors note that HPV-negative cases account for only “5%–15%” of high-grade vulvovaginal lesions.
Another limitation is the possibility that vaccinated women engage in overall healthier behaviours than unvaccinated women, which could overestimate risk reduction. Although the researchers adjusted for education and household income as proxies, they state that “we cannot completely rule out the possibility of residual confounding due to unaccounted-for factors, such as smoking and sexual activity, as these data are unavailable in registers.”
Finally, the observational design limits causal interpretation. The authors highlight that individuals vaccinated at 17 years or older had to remain event-free before vaccination, though they observed very few outcomes before vaccination across all groups.
Significance for India
Cervical cancer remains the second most common cancer among women in India, accounting for 22.86 per cent of all cancer cases in women and 12 per cent of all cancer cases overall.
In fact, according to a recent Lok Sabha reply, the estimated number of cervical cancer cases in India has shown a steady rise in recent years, underscoring a growing disease burden. The figures indicate 73,289 cases in 2019, increasing to 75,209 in 2020 and 77,130 in 2021, followed by 79,103 cases in 2022 and 81,121 cases in 2023. This upward trend highlights the urgent need for stronger preventive measures, including expanded screening and wider access to HPV vaccination.
As mentioned in a WHO article, “a national single-dose HPV vaccination programme for girls in India could substantially reduce the incidence of cervical cancer, to below the incidence rate set by WHO as the threshold for the elimination of cervical cancer as a public health problem. The threshold would be achieved both nationally and in each Indian state.”
Despite this potential, the HPV vaccine is not yet included in the Universal Immunisation Programme (UIP). A Lok Sabha reply noted, “Under the Universal Immunisation Programme (UIP), 11 vaccines are provided against 12 Vaccine Preventable Diseases (VPDs). Human Papilloma Virus (HPV) vaccine is not a part of the Universal Immunisation Programme (UIP).”
However, the Ministry of Health and Family Welfare has initiated “the capacity building exercise of medical and para-medical staff for the cervical cancer vaccine.”
Challenges in HPV vaccine uptake in India
Recent studies indicate significant gaps in awareness and uptake of the HPV vaccine in India. A 2024 survey in northern India involving 666 women aged 20 and above found that while 77.5 per cent had heard of cervical cancer, only 45.57 per cent had a sound understanding of its symptoms. Knowledge was lower among rural, less educated, and low-income women.
The study concluded that “critical gaps in cervical cancer awareness and vaccination willingness, particularly among socio-economically disadvantaged and rural women. In impoverished areas, targeted public health interventions including information campaigns and affordable HPV vaccines are needed to improve early stage identification and prevention.”
Another 2025 study in three districts of Punjab, covering 600 participants, revealed that although 90 per cent had heard of cervical cancer, only 1.8 per cent had comprehensive knowledge. Alarmingly, only 5.3 per cent had heard of the HPV vaccine, and just 0.5 per cent were vaccinated. Lack of knowledge (90.1 per cent) and high cost (5.9 per cent) were the main barriers.
The study emphasised, “diffuse knowledge about cervical cancer and low uptake of HPV vaccination in rural areas, not affected by sociodemographic characteristics. This calls for large-scale health advocacy programs to promote regular screening to generate demand and improve acceptance of the soon-to-be-launched indigenous HPV vaccine in the Universal Immunisation program and achieve the WHO global target of eliminating cervical cancer by 2030.”
Another systematic review covering studies from 2014 to 2024 identified key barriers to HPV vaccine uptake in India, including cost, lack of awareness, misinformation, and sociocultural factors. Facilitators included educational interventions, physician recommendations, and subsidised vaccination programs.
The review concluded, “Addressing economic and sociocultural barriers, enhancing awareness, and expanding targeted vaccination programs are essential to improve HPV vaccination rates in India. Aligning these efforts with the World Health Organisation’s 90/70/90 strategy can significantly reduce the cervical cancer burden.
This story is done in collaboration with First Check, which is the health journalism vertical of DataLEADS.