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Controversies in Internal Medicine |

Rebuttal by Dr Sawaya

George F. Sawaya, MD
Arch Intern Med. 2004;164(3):247-248. doi:10.1001/archinte.164.3.247.
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Mandelblatt et al raise excellent points and important issues. The strategy of adding a test for oncogenic HPV DNA in older women, for which many will have had prior normal test results, is intriguing and deserves thoughtful attention. Although the cited semi-Markov model assumes that HPV positivity by hybrid capture 2 (HC2) declines exponentially with age,1 recent prevalence studies demonstrate that HC2 positivity either increases to 12%2 or stabilizes at about 10%3,4 in women older than 60 years. Well-screened women have a low prevalence of cytologic abnormalities and cervical neoplasia. If as many as 10% are HC2-positive, clinicians should expect poor positive predictive value because of suboptimal HC2 specificity. The paradoxical association between non–high-risk HPV types and high-grade preinvasive disease in women older than 65 years also raises questions about test sensitivity.5 Importantly, the appropriate management of discordant women (those with normal cytologic findings and positive HC2 tests) is unknown.6 Future cost-effectiveness models must account for interventions in these women, as many will be screened annually indefinitely. Whether detection of oncogenic HPV DNA at this age represents new sexually transmitted infections or re-crudescence will be of great interest to some women. Unfortunately, few data currently exist to provide answers. Before testing, clinicians should be sensitive to individual women's desires to know their HPV status. Moreover, as part of informed decision making, clinicians should be forthright about the likelihood of discordancy, the uncertainty that exists surrounding its management, and the projected magnitude of the benefit conferred by adding this test.

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