Human Papillomavirus-Negative Cervical Cancer: A Comprehensive Review

Human papillomavirus (HPV) has been the leading cause of cervical cancer for over 25 years. Approximately 5.5-11% of all cervical cancers are reported to be HPV-negative, which can be attributed to truly negative and false-negative results. The truly HPV-negative cervical cancers are almost all cervical adenocarcinomas with unclear etiology. False HPV negativity can arise from histological misclassification, latent HPV infection, disruption of the targeting fragment, non-high risk HPV infection, and HPV testing methods. HPV-negative cervical cancers are often diagnosed at an advanced FIGO stage and have a poor prognosis; thus, the management of these cases requires greater attention.