medwireNews: Prophylactic vaccination against human papillomavirus (HPV) is highly effective in preventing cervical precancer in adolescent girls and young women, and is not associated with an elevated risk for serious adverse events, finds a Cochrane Library review.
The authors note, however, that the level of protection is lower for women older than 26 years and that longer follow-up is required “to monitor the impact on cervical cancer, occurrence of rare harms and pregnancy outcomes.”
They synthesized data from 26 trials, with over 70,000 participants, that assessed the monovalent, bivalent, or quadrivalent vaccines – which primarily target HPV types 16 and 18 – relative to controls. Ten of the included trials evaluated protection against the development of cervical intraepithelial neoplasia (CIN) and/or adenocarcinoma in situ (AIS), while 23 reported on safety outcomes.
Among adolescent girls and women aged 15–26 years who are negative for high-risk HPV, evidence of high certainty showed that vaccination was associated with a 99% reduced risk for CIN of grade 2 and above (CIN2+) as well as of grade 3 and above (CIN3+) associated with HPV 16/18. In absolute terms, there was a decrease in the number of cases from 164 to 2 per 10,000 women and 70 to 0 per 10,000 women, respectively.
The risk for HPV16/18-associated AIS was also lower in this subgroup for those who were versus were not vaccinated, with a 90% reduction in relative risk and an absolute reduction from 9 to 0 cases per 10,000 women, but the evidence for this was of moderate certainty.
The findings were similar for younger participants who tested negative for HPV16/18 DNA, with, for instance, a 95% reduced risk for CIN2+ associated with HPV16/18. This subgroup also allowed the researchers to assess the impact of vaccination among women aged over 26 years. They found that the vaccines afford protection but to a lesser degree; the risk for CIN2+ associated with HPV16/18 was 70% lower for vaccinated women relative to their unvaccinated counterparts.
Speaking to medwireNews, study author Marc Arbyn (Belgian Cancer Centre, Brussels) speculated that this difference could be because the older women may not be completely free of HPV – viral particles from a previously cleared infection may remain in the cervix lining at a level below the limit of detection of the currently used tests.
When all participants were considered regardless of HPV DNA status, vaccination remained associated with a reduced risk for CIN2+, CIN3+, and AIS in younger women. But there was no such reduction in the risk for CIN2+ among those aged 24–45 years and no study reported on the risks for CIN3+ and AIS in this age group.
Of note, the incidence of serious adverse events was comparable between vaccinated and control participants, as was the number of deaths.
Arbyn and colleagues did not observe an increased risk for miscarriage or termination among vaccinated women, but the impact on congenital abnormalities and stillbirths is uncertain and therefore an “[i]ncreased risk of adverse pregnancy outcomes after HPV vaccination cannot be excluded.”
The researchers conclude: “Long-term surveillance and registry-based research (linking of vaccination databases with screening, cyto-histopathology, cancer registries and biobanks; and linking with morbidity, mortality and birth/maternity registries) are needed to establish vaccine efficacy and safety over time.
“This will help also to assess type replacement, cross-protection, duration of protection associated with three or fewer doses and vaccine safety in pregnant women.”
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