Laboratory diagnosis of human papillomavirus infection

Human papillomaviruses (HPVs) are associated with numerous cutaneous or mucosal benign and malignant neoplasms. The majority of available data on routine HPV diagnostics has been centered on evaluating the cervix. Consequently, there is limited data on the utility and efficacy of HPV diagnostics in cutaneous lesions. Therefore the vast majority of data presented in this short review are derived from cervical cancer prevention measures. The balance between analytical (low) and clinical (high) sensitivity is crucial for the specificity of a routine HPV test as limited specificity would result in unnecessary treatment of healthy women. Furthermore, HPV-16 and -18 confer a much higher risk for the development of a cervical intraepithelial lesion 2+ compared to the other HPV high-risk types. It is therefore deemed appropriate to test for these HPV types independently. With the exception of testing for these HPV high-risk types, testing for individual HPV types is of very limited clinical value. Until now HPV diagnostics have mainly been based on DNA detection for which signal and target amplification methods are available. PCR techniques can be divided into type-specific and consensus PCRs. Due to its high clinical sensitivity and its relatively high specificity the Hybrid Capture 2 (HC2) test became the gold standard in routine HPV testing. The HC2 method hybridizes 13 (near) full-length stabilized RNA probes of high-risk HPV types to denatured target DNA followed by detection with antibodies and chemiluminescence. To avoid costly validation studies for new HPV tests, internationally accepted standards for evaluation have been defined. Meanwhile several new HPV detection assays have been commercialized. Three tests have received Food and Drug Administration approval (Cervista™, signal amplification; Cobas™ HPV test, real-time PCR; APTIMA™ HPV RNA test). Among them the Cobas HPV test has been most broadly validated for use in triage and as an adjunct to cytology. HPV RNA testing is another promising option with potentially higher specificity.