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Evidence summaries

Effect of Human Papillomavirus 16/18 L1 Virus Like Particle Vaccine Among Women with Pre-Existing Infection

In women positive for HPV DNA, HPV-16/18 vaccination appears not to reduce the risk of precancer lesions or accelerate clearance of the virus. Level of evidence: "B"

A Cochrane review [Abstract] 2 included 26 trials with a total of 73 428 participants. Persistent infection with high-risk human papillomaviruses (hrHPV) types is causally linked with the development of cervical intraepithelial neoplasia grade 2 and above (CIN2+), CIN grade 3 and above (CIN3+), and cervical cancer. HPV types 16 and 18 cause approximately 70% of cervical cancers worldwide. Regardless of HPV DNA statusin younger women (aged 15 to 26), HPV vaccines reduced the risk of CIN2+, CIN3+, and adenocarcinoma-in-situ (AIS) associated with HPV16/18. (table T1). The reduction in any CIN3+ differed by vaccine type (bivalent vaccine: RR 0.55, 95% CI 0.43 to 0.71 and quadrivalent vaccine: RR 0.81, 95% CI 0.69 to 0.96).In women vaccinated at 24 to 45 years of age, the risks of CIN2+ associated with HPV16/18 and any CIN2+ are similar between vaccinated and unvaccinated women, which may be due to previous exposure to HPV. Studies were not of sufficient power or duration to evaluate cervical cancer outcomes.

HPV vaccine effects on cervical lesions in adolescent girls and women unselected for HPV DNA status at baseline

OutcomeRelative effect(95% CI)RRRisk with placeboRisk with HPV vaccination (95% CI)№of participants(studies)Certainty of evidence
CIN2+ associated with HPV16/18Follow-up (age 15 to 26 years): 3.5 to 8.5 yearsRR 0.46(0.37 to 0.57341 per 10 000157 per 10 000(126 to 194)34 852(3) High
CIN2+ associated with HPV16/18Follow-up (age 24 to 45 years): 3.5 years0.74(0.52 to 1.05)145 per 10 000107 per 10 000(76 to 152)9 200(2) Moderate
CIN3+ associated with HPV16/18Follow-up: 3.5 years0.55(0.45 to 0.67)165 per 10 00091 per 10 000(74 to 127)34 562(2) High
Adeno carcinoma in situ (AIS) associated with HPV16/18Follow-up: 3.5 years0.36(0.17 to 0.78)14 per 10 0005 per 10 000(3 to 11)34 562(2) High
Any CIN2+ irrespective of HPV type(age 15 to 26 years) Follow-up : 3.5 to 8.5 years0.70(0.58 to 0.85)559 per 10 000391 per 10 000(324 to 475)35 779(4) High
Any CIN2+ irrespective of HPV type(age 24 to 45 years) Follow-up : 3.5 to 6 yearsRR 1.04(0.83 to 1.30)343 per 10 000356 per 10 000(284 to 445)9287(2) Moderate

In a randomised trial 1 in Costa Rica 2189 women (aged 18 to 25 years) with pre-existing infection were randomly assigned to receive 3 doses of a bivalent HPV-16/18 L1 protein viruslike particle AS04 candidate vaccine (n=1 088) or a control hepatitis A vaccine (n=1 101) over 6 months. Clearance rates for HPV-16/18 infections at 6 months were 33.4% (82/248) in the HPV vaccine group and 31.6% (95/298) in the control group (vaccine efficacy for viral clearance VEVC, 2.5%; 95% CI -9.8% to 13.5%) and at 12 months 48.8% (86/177) and 49.8% (110/220) respectively (VEVC -2.0%; 95% CI -24.3% to 16.3%). There was no evidence of a therapeutic effect for other oncogenic or nononcogenic HPV categories.

Comment: The quality of evidence is downgraded by study quality (more than 20% loss to follow up).

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    References

    • Hildesheim A, Herrero R, Wacholder S, Rodriguez AC, Solomon D, Bratti MC, Schiller JT, Gonzalez P, Dubin G, Porras C, Jimenez SE, Lowy DR, Costa Rican HPV Vaccine Trial Group. Effect of human papillomavirus 16/18 L1 viruslike particle vaccine among young women with preexisting infection: a randomized trial. JAMA 2007 Aug 15;298(7):743-53. [PubMed]
    • Arbyn M, Xu L, Simoens C et al. Prophylactic vaccination against human papillomaviruses to prevent cervical cancer and its precursors. Cochrane Database Syst Rev 2018;(5):CD009069. [PubMed]

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