Two new Cochrane reviews show strong and consistent evidence that HPV vaccines are effective in preventing cervical cancer and pre-cancerous changes, especially when given to young people before they are exposed to the virus.
Girls vaccinated before the age of 16 were found to be 80% less likely to develop cervical cancer. The reviews also confirm that HPV vaccines are only likely to cause minor, transient side effects such as a sore arm. The reviews were supported by the National Institute for Health and Care Research (NIHR).
Human papillomavirus (HPV) is a family of common viruses, including the viruses that cause skin warts. Whilst many types of HPV are harmless, other 'high-risk' types can cause cancers of the cervix, anus, penis, vulva, vagina, and throat, and others cause anogenital warts. Cervical cancer is the fourth most common cancer in women worldwide and causes more than 300,000 deaths each year, mostly in low- and middle-income countries. The new reviews confirm that vaccination against HPV can prevent most of these cancers from developing.
Clinical trial evidence supports effectiveness and safety
The first review focused on randomized controlled trials and included 60 studies with 157,414 participants. They found that all HPV vaccines were effective in preventing infections that can lead to cancer and other HPV-related conditions, with no evidence of serious safety concerns.
Because cancers caused by HPV can take many years to develop, most studies did not follow participants long enough to measure direct effects on cancer itself. However, vaccines such as Cervarix, Gardasil, and Gardasil-9 reduced precancerous changes in the cervix and other tissues in people aged 15 to 25 years, as well as the number of people needing treatment for HPV-related disease. The vaccines that included protection against the relevant HPV types significantly reduced the risk of anogenital warts.
Short-term side effects like mild pain or swelling at the injection site were common, but serious side effects were rare and occurred at similar rates in both vaccine and control groups.
"Clinical trials cannot yet give us the whole picture on cervical cancer, as HPV-related cancers can take many years to develop," says Hanna Bergman, co-lead author. "That being said, the evidence from these trials confirms that HPV vaccines are highly effective at preventing the infections that lead to cancer, without any sign of serious safety concerns."
Real-world evidence confirms long-term protection
The second review analyzed evidence from 225 studies involving more than 132 million people across multiple countries. It looked at observational study designs, including population-level studies comparing outcomes before and after introduction of the vaccine. Findings show that HPV vaccination clearly reduces the risk of developing cervical cancer and pre-cancerous changes of the cervix. The results came from studies of various designs across different follow-up periods.
Girls vaccinated at or before the age of 16 were 80% less likely to develop cervical cancer than unvaccinated girls. The review also found substantial reductions in pre-cancerous changes (known as CIN2+ and CIN3+), and in anogenital warts, which are also caused by HPV infection. Reductions were greater in people who received the HPV vaccine at or before the age of 16.
Importantly, the review found no evidence to support claims that HPV vaccination increases the risk of serious adverse events. By cross-referencing alleged adverse events with real-world follow-up data, the review team found no relationship between reported serious side effects and HPV vaccination.
"We now have clear and consistent evidence from around the world that HPV vaccination prevents cervical cancer," says Nicholas Henschke, co-lead author. "An important finding was that the commonly reported side effects of the vaccine, often discussed on social media, were found to hold no evidence of a real link to vaccination."
Global impact and next steps
Together, the two Cochrane reviews provide the most comprehensive and up-to-date evidence on HPV vaccination to date, drawing from both large-scale real-world studies and rigorous clinical trials. Evidence shows that HPV vaccination is a safe and highly effective public health measure, capable of preventing cancers that affect hundreds of thousands of people every year.
The findings underscore global recommendations to vaccinate both girls and boys, ideally before the age of 16, to achieve the greatest protection against HPV-related cancers. Protection is strongest when vaccination occurs before sexual debut and exposure to the virus.
"These reviews make it clear that HPV vaccination in early adolescence can prevent cancer and save lives," says Dr Jo Morrison, senior author, gynaecological oncology consultant at Somerset NHS Foundation Trust and Honorary Associate Professor at the University of Exeter. "Vaccinating boys as well as girls boosts protection for everyone. Over time we'll see the impact of vaccination on other cancers too, including ones that affect men."
However, the authors also note some evidence gaps. Most research has been conducted in high-income countries, meaning more studies are needed in low- and middle-income settings, where cervical cancer is more common and screening programs are lacking; it is in these countries that HPV vaccination will have an even more positive impact. However, to achieve the World Health Organisation's ambition to eradicate cervical cancer, high rates of HPV vaccination, cervical screening and treatment of pre-cancers detected by screening remain crucial.
"Longer-term data will continue to strengthen our understanding of how HPV vaccination protects against cancer over a lifetime. Whilst we now have sufficient data to see a beneficial effect of HPV vaccination on cervical cancers, which tend to develop in younger women, it will take decades to fully understand the impact of vaccination on vulval, peri-anal, penile and head and neck cancers which often develop later in life," says Dr Morrison.
