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Advances in primary and secondary interventions for cervical cancer: human papillomavirus prophylactic vaccines and testing

Nature Clinical Practice Oncology volume 4, pages 224–235 (2007)Cite this article

Abstract

Cytologic screening has greatly reduced the incidence of invasive cervical cancer in many industrialized nations. State-of-the-art cervical cancer prevention is costly, however, and includes cytologic screening at repeat intervals, confirmation of abnormalities by colposcopic biopsy, and treatment of precancerous lesions. In resource-limited settings, accessibility to prevention programs for cervical cancer is often poor, or such programs are simply unavailable or inadequately supported. This disease, therefore, remains a leading form of cancer among women living in low-resource regions, and over 250,000 women worldwide die from cervical cancer each year. Persistent cervical infection with one of approximately 15 carcinogenic human papillomavirus (HPV) types causes virtually all invasive cervical cancer and its precursor abnormalities, which can be detected by cytologic screening. Genital HPV infections are primarily transmitted via sexual intercourse. One promising prophylactic HPV vaccine is available and others continue in development as primary cervical cancer prevention strategies in younger women. As secondary interventions, HPV tests are simultaneously evolving for use in cervical cancer screening programs, including routine screening of older women. HPV testing is more sensitive and reproducible than cytology with colposcopy for the detection of cervical precancer and cancer. This article presents current advances and perspectives on HPV vaccines and HPV testing.

Key Points

  • Two current 'first-generation' HPV vaccines, Cervarix®, a vaccine against HPV types 16 and 18, and Gardasil®, a vaccine against HPV types 6, 11, 16, 18, demonstrate high efficacy in preventing genital precancers; Gardasil® additionally shows high efficacy in preventing external genital lesions caused by HPV types 6 and 11

  • Many HPV types not covered by these vaccines will still cause cervical cancer, and the vaccines demonstrate no significant therapeutic effect in women who are already infected with HPV vaccine types; we must therefore remain vigilant in continuing and improving cervical cancer screening programs

  • On the basis of phase II and III HPV vaccine results, prophylactic HPV vaccines appear generally safe and highly efficacious for up to 5 years, but little is currently known about duration of immunity, minimum protective markers of immunity, and potential requirements for booster vaccinations

  • The greatest benefit to the greatest number of women will be achieved by maximizing vaccine use in young women before sexual debut, and continuing and improving screening programs in sexually active older women who have been and who continue to be exposed to HPVs

  • Studies have demonstrated the utility of adjunctive HPV testing in the triage of equivocal Pap tests, in screening programs for women ≥30 years of age, and in monitoring treatment of cervical precancers, and results strongly suggest that HPV tests may be viable as primary screening tests

  • We must overcome disparities and bring opportunities for advances in cervical cancer prevention to those with the greatest need and determine the optimum use and relative roles of prophylactic HPV vaccines and HPV testing within varied resource settings

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Figure 1: Schematic diagram to show the disease continuum of cervical neoplasia development following human papillomavirus infection
Figure 2: The worldwide estimated positive fraction of human papillomavirus types 16 and 18 among cervical abnormalities of increasing severity, for cervical cancer, high-grade squamous intraepithelial lesions, low-grade squamous intraepithelial lesions, and atypical squamous cells of undetermined significance

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Author notes

  1. Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, House of Prevention Epidemiology, Building 191, 1816 Sigma Chi Road, Albuquerque, NM 87131, USA cwheeler@salud.unm.edu

Authors and Affiliations

  1. Department of Molecular Genetics and Microbiology, CM Wheeler is Professor and Chief of Translational Research, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.,

    Cosette M Wheeler

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CM Wheeler has declared she has research contracts with GlaxoSmithKline and Merck and for HPV vaccine trials.

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Wheeler, C. Advances in primary and secondary interventions for cervical cancer: human papillomavirus prophylactic vaccines and testing. Nat Rev Clin Oncol 4, 224–235 (2007). https://doi.org/10.1038/ncponc0770

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