The future of HPV testing in clinical laboratories and applied virology research

Abstract

Background: Human papillomaviruses (HPV) are now considered etiologic agents of cancer of the uterine cervix. Adjunctive diagnostic procedures for the detection of HPV infection could increase the sensitivity of primary and secondary screening of cervical cancer. HPV testing could also improve the specificity of screening programs resulting in avoidance of overtreatment and saving of costs for confirmatory procedures. Objectives: To review the rationale of HPV testing in genital diseases and the potential applications of HPV DNA detection methods for clinical and epidemiological purposes. Results: Progression of HPV infection is associated with the persistence of HPV infection, involvement of high-risk HPV types, high HPV viral load in specimens, integration of viral DNA and possibly the presence of cofactors. The design of HPV diagnostic tests will need to take into account these parameters of disease progression. HPV DNA detection techniques based on signal-amplification are standardized, commercially available and detect several high-risk HPV types. They increase the sensitivity of screening for high-grade and low-grade lesions. Although they may yield false-negative results in the presence of significant HPV-related disease, new test formats could resolve this weakness. Amplification techniques are ideal instruments for epidemiologic purposes since they minimize misclassification of HPV infection status and allow for the detection of low viral burden infections. They are currently not readily applicable to diagnostic laboratories. Conclusions: Before recommending HPV testing, prospective trials of untreated LSIL with HPV testing as well as the determination of the efficacy and cost-effectiveness of novel HPV tests, need to be completed.