[PubMed] [CrossRef] [Google Scholar] 11. cancer screening, triage of HPV screen-positive women, monitoring HPV vaccine impact, and HPV testing in groups for which a less invasive sample is preferred. Detection of cell-free DNA (including HPV DNA) in blood has great promise for the early detection of HPV-attributable oropharyngeal cancer (HPV-AOC) and potentially other HPV-driven cancers and as an adjunct prognostic marker in long-term tumor surveillance, including treatment response. The moderate sensitivity of HPV testing in oral rinses or swabs at HPV-AOC diagnosis prevents its use in HPV-AOC secondary prevention but represents a promising prognostic tool in HPV-AOC tertiary prevention, where the HPV persistence in oral rinses throughout treatment may predict early HPV-AOC recurrences and/or the development of secondary HPV-AOC. The increasing sophistication of specific collection devices designed for alternative samples and the enhanced precision of novel molecular technologies are likely to support the evolution of this field and catalyze potential translation into routine practice. KEYWORDS: HPV, urine, blood, oral specimens, cervical cancer, oropharyngeal cancer Elagolix sodium INTRODUCTION Human papillomaviruses (HPVs) have a remarkably stable DNA genome and are classified by the homology of their genome into five genera (genus with Elagolix sodium highest oncogenic potential are often referred to as high-risk HPV genotypes (hrHPVs) and are Elagolix sodium as follows: HPV-16, -18, -31, -33, -35, -39, -45, -51, -52, -56, -58, and -59 (3, 4). Most hrHPV infections follow a subclinical course, but some persistent infections are etiologically linked with benign and malignant lesions of the epithelia (4, 5). Human cancers attributable to hrHPVs represent 4.5% of all cancers worldwide (8.8% and 0.9% of all cancers in women and men, respectively), with approximately 690,000 new cancer cases identified each year (6). hrHPVs cause virtually all cervical and anal cancers, a substantial proportion of vaginal cancers, and a component of oropharyngeal, penile, and vulvar cancer (5, 6). Consequently, laboratory detection of HPV to support screening for (or management of) associated disease has been the subject of research and development since the 1980s, of which some has translated into large-scale screening practice. Furthermore, general improvements in the Ephb4 precision of molecular testing and in our understanding of the natural history of HPV infection have ensured that the laboratory detection of HPV is still a highly dynamic field. In this review, we reflect on the importance of tailoring the HPV test to the application and discuss the following three key and expanding areas in the laboratory detection of HPV: testing of urine, testing of blood, and testing of oral samples. Implications of this expansion for the detection and management of the two most common hrHPV driven cancers, namely, cervical and oropharyngeal, are our focus. THE BURDEN OF CERVICAL AND OROPHARYNGEAL CANCER AND THE IMPORTANCE OF EVIDENCE-BASED INTERVENTIONS Cervical cancer, with 570,000 new annual cases worldwide, is the hrHPV-driven cancer associated with the greatest morbidity and mortality (6). Because hrHPVs are found in nearly all cases of cervical Elagolix sodium cancer, the etiological association between persistent hrHPV infection and this cancer is Elagolix sodium very strong, consistent, specific, and universal, making cervical cancer a highly credible target for public health preventive interventions, including through vaccination and screening. Although primary prevention via prophylactic HPV vaccination is a key tool for the elimination of cervical cancer (and other HPV-related cancers), the secondary prevention of cervical cancer via sensitive HPV-based screening using molecular tests is crucial and will be necessary for at least the next 50?years and will significantly accelerate the pace of cancer reduction (7,C9). Increased access to HPV-based screening in hard to reach populations, including those in low- and middle-income countries will be essential if the goal of cervical cancer elimination is to be reached (7). The use of self-taken samples, including urine samples, is a clear way to support equitable access as will be discussed. Oropharyngeal cancer is the second most common hrHPV-related human cancer, which is traditionally associated with chronic exposure to tobacco, heavy alcohol consumption, and deprivation (10). However, in the last 2 to 3 3 decades, hrHPV has emerged as an etiological agent for a subset of oropharyngeal cancer.