Prognostic Value of Measuring Load of Human Papillomavirus DNA in Cervical Samples: An Elusive Target

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Detection of DNA of high–oncogenic-risk human papillomaviruses (HPVs) in cervical cells is increasingly gaining acceptance in primary screening for cervical cancer ( 1 ). HPV testing is not only more accurate than Papanicolaou cytology for revealing preexisting cervical precancerous lesions ( 2 ) but also more prognostic than the latter test with respect to the subsequent risk of lesions in women who are lesion free at first screening ( 3 ). It thus stands to reason that the extent of the predictive value of HPV testing, both cross-sectionally and prospectively, can be augmented by taking into account ancillary measurements of viral load in cervical specimens. A high viral load may indicate a productive HPV infection, which is common in low-grade squamous intraepithelial lesions. Productive viral replication may also result from a primary infection in which host immune control has not yet been developed. In the absence of cytologic abnormalities, a high HPV load may be indicative of an infection that is likely to persist and thus be more prone to develop into a dysplastic lesion. Alternatively, a high HPV DNA load may result from testing a cervical sample that has an abundance of dysplastic cells relative to the background of normal cells that are coexfoliated during specimen taking, thus revealing a high-volume lesion. Therefore, regardless of mechanism, there is plausibility for the expectation that measuring HPV DNA load in cervical samples may be associated with clinical outcomes and thus serve as an additional biomarker in cervical carcinogenesis.