FDA-APPROVED MOLECULAR TESTS USED TO DEFINE HUMAN PAPILLOMAVIRUS (HPV) INFECTIONS WHICH CAUSE CERVIX CANCER

Abstract

Human papillomavirus (HPV) is a non-enveloped, commonly sexually transmitted virus with icosahedral symmetry and double-stranded circular DNA. Its genome, which is about 8 kb in size, encodes early genes (E1-8) and two late structural capsid genes (L1 and L2). Among the genes that play a role in viral pathogenesis, L1, E6, and E7 genes frequently exist. The E6 and E7 viral genes have a significant role in apoptosis inhibition, viral spread, development of squamous intraepithelial lesion (SIL), cell immortalization, neoplastic transformation, and invasive cancer. Demonstration of the relationship between cervical cancer and HPV infections has led to increased interest in this subject and the classification of some HPV genotypes in the high-risk group (HR-HPV) for cervical cancer. Numerous commercial molecular tests have been developed for the identification of HPV genotypes involving different approaches. HPV molecular tests approved by the US Food and Drug Administration (FDA) include Hybrid Capture® 2 (HC2), Cervista™, cobas®, Aptima®, and BD Onclarity™. This article reviews the methodologies, limitations, and commonalities of five FDA-approved tests. The HC2 and Cervista™ tests use non-PCR-based signal amplification methods, while the cobas® and BD Onclarity™ tests use PCR-based target amplification methods. On the other hand, the Aptima® test uses the mRNA transcriptional mediated amplification (TMA) method. Each of these methods used in the diagnosis and follow-up of HPV has its strengths and weaknesses. These HPV molecular tests have high sensitivity and specificity. They are also more automated and repeatable than cytological methods. In addition to these advantages, there are also several limitations. Because of these limitations, molecular tests are no more perfect than cytological tests. This situation shows that these tests should not be used alone in the evaluation of HPV infections and cancer identification. On the contrary, HPV test results should be correlated with cytology or biopsy findings.