HPV vaccines are unsafe

Cochrane

Human papilloma viruses (HPV) are a group of viruses that affect the skin and mucous membranes. Some types of HPV are sexually transmitted and are common in young people. Most infections are blocked by the immune system, but some people remain infected with certain types of HPV, which cause changes (abnormalities) in the cells that are infected. These changes are known as "precancerous lesions" because they can develop into cancers that affect the cervix, vagina, pubic area, anal canal, penis, head, and neck. Infections with other types of HPV cause warts to develop in the genital area or around the anus.

The aim of vaccination is to prevent future HPV infections. Three HPV vaccines are used - one bivalent (protects against two types of HPV), one quadrivalent (protects against four types of HPV), and one nonavalent (protects against nine types of HPV). In women, three doses of the bivalent or quadrivalent HPV vaccine protect against early-stage cervical cancer from the types of HPV given by the vaccine. Evidence on nonavalent vaccination, the effects of quadrivalent vaccination in men, and the effects of HPV vaccination in people with HIV has not yet been thoroughly summarized. The take-up of HPV vaccinations is still low in many countries. Simplified vaccination schedules or giving the vaccine to both girls and boys could increase the number of people vaccinated.

HPV vaccination studies are not always designed to collect data on cancer or early-stage cancer for a variety of reasons. First, the HPV vaccine is routinely given before girls become sexually active and it is not ethical to take samples from the wombs of girls who have never had sexual intercourse. Second, HPV-related precancerous lesions and cancer are rare and do not develop until years after the time of infection. Third, study participants are offered treatments in the event of early-stage cancer. Therefore, cervical cancer would be even less likely to develop, even without vaccination. An international committee of experts has determined that, under certain circumstances, antibody levels (i.e. a strong immune response) can be used to indicate protection against cervical and anal cancer. The antibody levels detected after vaccination in one study should not be lower than those in other studies in adults in which the vaccination has been shown to protect against severe, HPV-related disease of the uterus or the anal area.

Question

How effective or harmful are different HPV vaccination schedules (i.e., the number and timing of doses given) and different HPV vaccines in men and women?

Main results

These results are based on research evidence as of September 27, 2018. We examined 20 studies with 31,940 participants.

Studies comparing two doses of HPV vaccines administered to three doses administered, or the time interval between doses, focused on immune system responses (immune responses) rather than infection or disease-related endpoints. Two doses of HPV vaccine produce similar immune responses as three doses, and a longer interval (up to 12 months) between doses results in a stronger immune response than a shorter interval. There is insufficient evidence on whether there was a difference between vaccination schedules for serious adverse events and deaths.

One study provided evidence of moderate reliability that in 16 to 26-year-old men a quadrivalent HPV vaccination offers better protection against external genital lesions and warts than a sham treatment (control). In women aged 16 to 26, a study showed that nonavalent and quadrivalent vaccinations offer similarly good protection against pre-cancerous lesions and cancer in the uterus, vagina and pubic area (evidence of high trustworthiness).

There was evidence that quadrivalent vaccination resulted in more local adverse events (such as pain, swelling, and redness at the injection site) in men than controls, and that nonavalent vaccination produced more local adverse events in men and women than quadrivalent vaccination. The evidence on serious adverse events and deaths from studies comparing different HPV vaccine types or dose regimens was of low or very low confidence.

HPV vaccines produce acceptable levels of immune responses in people with HIV. However, the evidence on the effects and harms for persistent HPV infection or for HPV-related disease-related endpoints is limited.

Trustworthiness of the evidence

With regard to the methodological quality of the studies to measure infection and disease endpoints or immune responses, no major problems were found. Our confidence in the evidence of serious harm or death across all studies comparing different HPV vaccination schedules and types is low - either because of its rarity or because the evidence is indirect, or both. A high level of confidence in the evidence means that we can say with confidence that further research is unlikely to affect our results. With moderate confidence in the evidence, there is a chance that further research could have a significant impact on our results, while low confidence evidence means that our confidence was compromised and further research could significantly affect our results. Very low confidence evidence means that we were unsure of the outcome.

conclusion

A two-dose regimen of HPV vaccine produces an immune response comparable to that of a three-dose regimen in young women. In men, quadrivalent vaccination appears to be effective in preventing external genital lesions and warts. Quadrivalent and nonavalent HPV vaccines provide similar protection against precancerous lesions and cancer of the uterus, vagina, and pubic in young women. The evidence on effectiveness and harm in people with HIV is limited. More long-term population-level studies are needed to continue to monitor the safety of these vaccines, to determine how long two doses of the vaccine can protect against HPV-related disease, to see what effect they have against HPV-related cancer and whether a two-dose schedule increases the rate of vaccination in the population.