Genitoanal human papillomavirus infection and associated neoplasias

Abstract

Human papillomavirus (HPV) infection is the most common sexually transmitted virus infection; about 40 out of 150 known HPV genotypes have been associated with genitoanal lesions in the female and male. They have been divided into low-risk (LR) and high-risk (HR) HPV types according to the association of each HPV genotype with genitoanal benign warts, genitoanal cancer and precursor lesions. For the most part, genitoanal HPV infection is equally common in men and in women. Genitoanal HPVs are predominantly transmitted by sexual intercourse. In a minor number of individuals where HR HPV infection has persisted, malignant squamous-cell tumors may develop. There are 15 mucosal oncogenic HPV types which are the etiological factor of cervical cancer and other genitoanal cancers. DNAs of HR HPV types are present in 100% of all cervical carcinomas and in 100% of the precursor lesions, the cervical intraepithelial neoplasias 2 and 3. HPV-16 and -18 alone account for 70% of the oncogenic mucosal HPV types identified. HR HPV types, mostly HPV-16 and -18, are the causes of vaginal and vulvar cancers in females, anal cancers in both genders and cancer of the penis in men. While anal cancers are linked to HR HPVs in more than 80% of cases, only 40% of vulvar cancers and 50% of penile cancers are HPV positive. Genitoanal cancers have a similar anatomy, histology and similar risk factors as well as natural histories. About 60% of vulvar and 50% of penile cancers are HPV negative, but associated with chronic inflammatory disorders, mainly lichen sclerosus. Clinical manifestations of LR HPVs in both sexes are genitoanal warts (condylomata acuminata), which are benign highly infectious tumors. The highest rate of warts is observed in females 16-24 years of age. In males the peak is at the age of 20-24 years. Diagnosis of genitoanal warts should exclude other sexually transmitted infections and diseases. A high number of genitoanal dermatoses, benign tumors, malignant squamous-cell neoplasias and cancer precursors may mimic condylomata acuminata. These malignant counterparts have to be ruled out by biopsy and a thorough histological workup. Therapy of manifest genitoanal HPV-associated lesions has profited from the development of local immunotherapy with imiquimod and local therapy with green tea derivatives (sinecatechin) 10% (Europe) and 15% (USA). Disease recurrence is a crucial problem with treatment, one that could potentially be reduced with the use of immunomodulating agents such as immuquimod and sinecatachins. Recently primary prevention of genitoanal clinical manifestations associated with HPV-6, -11, -16 and -18 including cancer precursors (intraepithelial neoplasias) has become true by the release of prophylactic quadrivalent (HPV-6, -11, -16, -18) and bivalent (HPV-16, -18) vaccines. These vaccines consist of HPV L1 virus-like particles which induce high anti-L1 serum-neutralizing antibody concentrations. Dermatologists and venereologists, general practitioners and pediatricians should cooperate with gynecologists to vaccinate young women and men in order to increase vaccination rates. In Australia and Scotland, an immense efficacy has been observed both regarding the prevention of benign genitoanal warts and cancer precursors caused by the vaccine HPV types. An absolute prerequisite of such a successful prevention against HPV-associated neoplasias is the administration of the vaccine before the first sexual contact.