HPV Genotyping in the Prevention of Cervical Cancer—How and When Can It Be a Useful Marker?

Abstract

Persistent infection with high-risk human papillomavirus (hrHPV) types is the known cause of cervical cancer (1), a neoplasia suitable to effective primary and secondary prevention. For many decades, cervical cancer screening has been performed by cytology as the primary test, with significant reductions in cancer incidence (2), and, more recently, the use of hrHPV testing with cytology triage in large randomized controlled trials (RCT) has been demonstrated more effective than cytology in preventing invasive cervical cancer (3). The aim of screening is the prevention of cervical cancer through detection and excision of precursor lesions (namely, CIN2 and worse), and its effectiveness, besides primary test performance, depends on target population coverage and adherence to quality-controlled protocols; organized population-based screening is more cost-effective than opportunistic testing.HPV-based screening is more sensitive than cytology-based screening given the use of clinically validated tests for hrHPV types (4), in women 30 years and older, and triage of HPV-positive cases to counterbalance the 2.5% to 4% lower specificity (3). HPV infection is transient in the vast majority of the women (and particularly in those younger than 30-35 years of age) and only a minority harbor a persistent infection and have or are at risk of having a high-grade lesion (5). Spontaneous regression of CIN2 and, to a lesser extent, CIN3 lesions also occurs in a proportion of women and is more frequent in the youngest. Therefore, triage is necessary to select the women at higher risk of precancer who need immediate colposcopy, thus limiting excessive referral and overdiagnosis in women with transient and not (or less) clinically relevant HPV infections. Cytology is actually the most widely used test to triage hrHPV-positive women attending organized screening (6), but search for alternative (and less subjective) tests is advocated. Several studies, investigating p16 expression, HPV genotyping, HPV mRNA expression, and methylation of cellular and/or viral sequences as triage markers (used alone or in combination) have been published so far (7-12). These markers have been analyzed in terms of immediate or subsequent risk of CIN2 þ or CIN3 þ , sensitivity, specificity, positive predictive value, and cost-effectiveness (colposcopy referrals, overdiagnosis, and harms). These analyses have been performed on different populations (clinical settings or population-based screening), of different ages, cross-sectionally only or longitudinally. Overall, HPV16 has always been associated with the highest risk of CIN2 þ and CIN3 þ , with a three-tier ranking of the other hrHPV types; risks were highest in the first screening round, gradually decreasing over time but still persisting after more than 9 years (12). Moreover, an inverse relationship between sensitivity and specificity of the triage tests was always registered, and different combinations have been proposed. Indeed, the ideal triage test/strategy should allow selection of women at hig...

Experience destructive therapy anogenital warts

“…Этиологический агент аногенитальных бородавок -вирус папилломы человека (ВПч) -является высококонтагиозным эпителиотропным вирусом, передаваемым от человека к человеку при оральном, генитальном и анальном половых контактах, а также контактно-бытовым и вертикальным путями. Поражая эпителиальные клетки, ВПч паразитирует в эписомальной, а затем и в интегрированной форме, при определенных условиях запуская процесс канцерогенеза [5,6].…”