PL8 The causal role of genital human papillomavirus (hpv) infections in cervical carcinogenesis

Abstract

Well over 150 different human papillomavirus (HPV) types are currently recognised, divided according to their preferential targets into (i) cutaneous and (ii) mucosal HPV types. The latter are further classified as low‐risk (HPV 6, 11, 40, 42, 43, 44, 54, 61, 70, 72, 81, and CP6108), intermediate risk (HPV 26, 53, and 66) and high‐risk (HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, and 82) types, according to their association with malignant lesions at genital‐ and extra‐genital mucosal sites. Since the recognition of their close association with cervical cancer precursor (CIN) lesions in 1976, HPVs have emerged as the most important human tumour viruses. Beyond any doubt, oncogenic HPV types are the single most important etiological agents of cervical cancer (CC) and CIN lesions, whereas low‐risk HPV types are associated with benign mucosal squamous cell lesions (papillomas and condylomas). Apart from extensive epidemiological documentation, the link between HPV and CC has been confirmed by molecular biological research and prospective cohort studies disclosing the natural history of HPV infections and the true precancer nature of high‐grade CIN lesions. The latter develop as a result of persistent oncogenic HPV infections, known to predispose the women to significantly increased risk of CC. Factors predicting both the disease outcome (persistence, progression, regression) and the viral events (incident infections, HPV persistence, virus clearance) are emerging only recently. In addition to testing the feasibility of various optional screening tools in early detection of CC precursors, as well as to ongoing clinical trials with prophylactic HPV vaccines, another major focus of current HPV research includes the intense screening of new biomarkers as potential predictors of disease progression and outcome of oncogenic HPV infections.