Molecular diagnosis and monitoring of human papillomavirus infections

Abstract

Though the incidence of cervical cancer is low in the USA, cervical cancer is still the second leading cause of cancer and cancer-related deaths worldwide [1]. The Papanicolou (PAP) smear has been the hallmark of cervical cancer screening since 1949. Following the discovery that HPV was the causative agent in >99 % of cervical cancers [2], the detection of high-risk HPV types (HRHPV) that cause cervical cancer in cervical samples became an important adjunct in the cervical cancer screening algorithm [3, 4]. Currently, HPV DNA testing is recommended in cervical cancer screening as a co-test to the Pap test and as a reflex test for cytology samples determined to be atypical squamous cells of undetermined significance (ASCUS) [5]. Both of these recommendations are only in women over 30 years old (>30). Though HRHPV types were universally found in cervical cancer, infection by HRHPV types results in cervical cancer in a very small percentage of infections [6]. More recently, new- or second-generation cervical cancer diagnostics targeting different aspects of the mechanism of cervical cancer pathogenesis have been brought into clinical use and added much needed specificity to the cervical cancer screening algorithm [7]. The purpose of this chapter is to understand the utility of HPV/cervical cancer diagnostics. In particular, discussion focuses on the relationship between the diagnostic target and the pathogenesis of cervical cancer as the field attempts to direct diagnostics toward detection of lesions requiring treatment and minimize the number of women sent to unnecessary, invasive procedures. In other words, cervical cancer diagnostics to date have focused on the mere presence of HRHPV and the associated risk of developing cervical cancer rather than the HPV-driven mechanism by which HPV causes cervical cancer. In this chapter, consideration is also given to other uses of HPV diagnostics including anal and head and neck cancers.