College of American Pathologists
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CAP Today



February 2008
PAP/NGC Programs Review

David C. Wilbur, MD

The introduction of vaccines for human papillomavirus, or HPV, and the widespread use of HPV testing may significantly alter the mode and method of cervical cancer screening programs. In a recent article published in Cancer Cytopathology, Mark Schiffman, MD, MPH, of the National Cancer Institute, details many predictions about how this process might play out (Integration of human papillomavirus vaccination, cytology, and human papillomavirus testing. Cancer [Cancer Cytopathol]. 2007; 111: 145– 153).

In the article, Dr. Schiffman provides background information relevant to human papillomavirus and its association with cervical cancer. HPV infections are common and most typically associated with no cytologic abnormality or only with minor abnormalities such as atypical squamous cells. HPV 16 is the most common type associated with persistent infections and with the subsequent development of high-grade cervical intraepithelial lesions and cervical cancer. Dr. Schiffman then proceeds to discuss the two new vaccines that protect against HPV 6 and HPV 11, the causes of genital warts (Merck), and HPV 16 and HPV 18, the types most commonly associated with cervical cancer (Merck and GlaxoSmithKline). Widespread vaccination would reduce the numbers of high-grade lesions caused by HPV types 16 and 18, hence decreasing the positive predictive value for high-grade disease of cytologic changes interpreted as atypical squamous cells or as low-grade squamous intraepithelial lesions. This loss of positive predictive value for high-grade disease would extend to colposcopic examination as well. In addition, positive predictive value for high-grade disease would also be degraded for the currently used non-type–specific HPV testing programs because positive tests would be more likely to represent infections with other, less oncogenic-associated types of HPV.

Dr. Schiffman then conjectures how current cervical screening programs might be affected in the post-vaccine implementation era. Given that younger girls are those for whom vaccination is recommended, he postulates that vaccination among older individuals will be more sporadic and thus that population will continue to require routine screening in the current mode without modification. In the highly vaccinated younger population, however, the age of first screening will most likely be greater; he suggests 24 years. In addition, screening intervals are likely to be lengthened, and screening will probably consist of a Pap test performed in conjunction with a type-specific HPV test, the latter screening only for high-risk types such as 16 and 18. Pap test volumes may decrease significantly, by as much as 50 percent based on these potential changes in practice. Given the lower prevalence of high-grade disease in the population, the use of automated screening instruments for the primary screening of Pap tests may be preferred. Such technologies do not suffer from the well-known phenomenon of human habituation that leads to diminished screening sensitivity in populations with low disease prevalence.

Overall, the article conveys the basic material that is relevant to cervical cancer screening in the post-vaccination era. Though screening programs in this context have yet to evolve, the conjectures made here are likely, at least in a general sense, to hold true. The article represents essential background reading for anyone interested in what cervical cancer screening might look like in the future and how this very hot topic area may play out.

Dr. Wilbur, chair of the CAP Cytopathology Committee, is director of cytopathology, Massachusetts General Hospital, Boston.