Medicine by the Numbers

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HPV Vaccine for Prevention of High-Grade Precancerous Cervical Lesions


Am Fam Physician. 2019 Apr 1;99(7):online.


Details for This Review

Study Population: Females 15 to 45 years of age who received human papillomavirus (HPV) vaccines (monovalent, bivalent [Cervarix], and quadrivalent [Gardasil])

Efficacy End Points: Rates of high-grade precancerous cervical lesions (cervical intraepithelial neoplasia [CIN] grade 2 or 3) and adenocarcinoma in situ in young women

Harm End Points: Adverse effects at site of administration, including local pain, swelling, redness, and itching; systemic effects, mortality, and effects related to miscarriage

Narrative: Cervical cancer mortality has decreased in incidence since the adoption of routine screening with the Papanicolaou smear. Despite screening, cervical cancer was responsible for 266,000 deaths worldwide in 2012.1 Precancerous cervical lesions and cervical cancer are caused by HPV in 99% of cases.2 Persistent infection with certain types of HPV, referred to as high-risk HPV (hrHPV) strains, are more likely to lead to cervical cancer than other types. Of the hrHPV types, HPV types 16 and 18 are associated with 70% of all cervical cancers. Several vaccinations targeted against HPV have been developed with the goal of reducing cervical cancer and mortality.

The systematic Cochrane review included 26 randomized controlled trials (N = 73,428) evaluating the efficacy and safety of HPV vaccines compared with placebo.3 Results were separated into three groups based on exposure to HPV at enrollment: hrHPV-negative (15 to 25 years of age); HPV types 16- or 18-negative; or undisclosed HPV status. Women who were negative for any hrHPV appeared to receive the greatest benefit from vaccination, with a number needed to treat (NNT) of 55 for preventing any precancerous lesions (risk reduced from 287 to 106 per 10,000; relative risk [RR] = 0.37; 95% CI, 0.25 to 0.55). For lesions associated with HPV types 16 or 18 in this group, the NNT was 62 (risk reduced from 164 to 2 per 10,000; RR = 0.01; 95% CI, 0 to 0.05). In women who tested negative for HPV types 16 and 18 at enrollment, the results differed based on age. Females 15 to 25 years of age had an NNT of 73 for preventing any precancerous lesion (risk reduced from 231 to 95 per 10,000); women older than 25 years demonstrated an NNT of 322 for this outcome (risk reduced from 45 to 14 per 10,000). A difference in results based on age was also noted in the undisclosed HPV status group. The NNT for preventing any precancerous lesion

Author disclosure: No relevant financial affiliations.

The opinions and assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the United States Army medical corps or the U.S. Army at large.

Copyright © 2019 MD Aware, LLC ( Used with permission.

This series is coordinated by Dean A. Seehusen, MD, MPH, AFP Assistant Medical Editor, and Daniel Runde, MD, from the NNT Group.

A collection of Medicine by the Numbers published in AFP is available at


1. Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136(5):E359–386.

2. Rerucha CM, Caro RJ, Wheeler VL. Cervical cancer screening. Am Fam Physician. 2018;97(7):441–448.

3. Arbyn M, Xu L, Simoens C, Martin-Hirsch PP. Prophylactic vaccination against human papillomaviruses to prevent cervical cancer and its precursors. Cochrane Database Syst Rev. 2018;(5):CD009069.



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