Human papillomavirus (HPV) vaccination in women aged 15 to 26 years showed “high-certainty evidence” for protecting against cervical precancer, according to a new analysis published in the Cochrane Library.

Some types of HPV can develop into cervical lesions, including the high-risk HPV16 and HPV18 that account for ~70% of cervical cancer cases worldwide. To examine associations between HPV vaccination and cervical cancer, the researchers analyzed 26 randomized studies (N=73,428) of which 3 trials included women aged 25 to 45 years old. The studies included monovalent, bivalent, and quadrivalent vaccines. 

The data in most studies were not long-term enough nor large enough to measure cervical cancer outcomes. The researchers instead analyzed HPV vaccination and precancer cervical lesions in the 10 trials that had follow-up periods of ≤8 years. Specifically, they looked at precancer cervical lesions (cervical intraepithelial neoplasia grade ≥2 [CIN2+], CIN grade ≥3 [CIN3+], and adenocarcinoma-in-situ [AIS]) and safety as related to vaccine HPV types and independent of HPV types.

Results showed that in young women (aged 15 to 26 years) who were high-risk HPV (hrHPV)negative , the vaccine reduced CIN2+, CIN3+, and AIS associated with HPV16/18 vs control. High-certainty evidence was seen with the risk of CIN2+ decreasing from 164 per 10,000 women to 2 per 10,000 women (RR 0.01), and the risk of CIN3+ decreasing from 70 to 0 per 10,000 women (RR 0.01). Moderate-certainty evidence indicated a reduced risk of AIS with vaccination from 9 to 0 per 10,000 women (RR 0.10). 

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The HPV vaccines reduced the risk of any CIN2+ from 287 to 106 per 10,000 (RR 0.37; high certainty). For patients who were HPV16/18 negative and aged 15 to 26 years, the vaccines were associated with a reduction in CIN2+ associated with HPV16/18 from 113 to 6 per 10,000 (RR 0.30). The risk reduction was smaller in particular for women aged ≥24 years. 

Regardless of patients’ HPV status, the vaccines were shown to reduce any CIN2+ from 559 to 391 per 10,000 (RR 0.70; high certainty) and any AIS from 17 to 5 per 10,000 (RR 0.32; high certainty). For the reduction in any CIN3+, the bivalent vaccine had an RR of 0.55 and the quadrivalent vaccine had an RR of 0.81.

There were 11 deaths in the control group and 14 in the vaccine groups (RR 1.29; low certainty); no pattern in the cause or timing of death was established. The risk of serious adverse events was similar for both control and vaccine groups (669 vs 656 per 10,000, RR 0.98; high certainty). 

The analysis found that HPV vaccination did not have the same protective effect for older women (25 to 45 years) on precancer, possibly due to previous HPV exposure. The risk of any precancer is probably similar between women who were vaccinated and unvaccinated (356 vs 343 per 10,000; moderate certainty). 

The authors concluded, “There is high-certainty evidence that HPV vaccines protect against cervical precancer in adolescent girls and young women aged 15 to 26,” while adding that future studies should have long-term follow-up to determine the impact on cervical caner

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