© Springer-Verlag Berlin Heidelberg 2015Vincenzo Mirone (ed.)Clinical Uro-Andrology10.1007/978-3-662-45018-5_14
14. HPV Infection in Male
Department of Clinical and Experimental Medicine, University of Florence, Largo Brambilla 4, Florence, Italy
Department of Urology, Santa Chiara Regional Hospital, Largo Medaglie d’Oro, 9, Trento, Italy
14.3.2 HPV Infection and Fertility
14.6.2 Secondary Prevention
KeywordsHuman papillomavirusMaleProstatitisUrogenital neoplasmsPapillomavirus vaccines
14.1 Epidemiology of HPV Infection
Human papillomavirus (HPV) infection is commonly recognized as the first cause of cervical cancer in women as well as other diseases in men and women (Garnock-Jones and Giuliano 2011). About 97 % of cervical cancers take its origin by a sexually transmitted viral infection that subsequently evolved to cancer transformation through the persistence of HPV into the cervical mucosa for long periods of time (till 20–30 years) (Tay 2012). Viral transmission normally occurs through sexual intercourse with commonly recognized infection distribution from man to woman or man to man where man is often considered as a disease healthy bearer. The viral passage from woman to man has been demonstrated and clarified in clinical practice only in the cases of anogenital warts in the sexual partner. In all these cases man represents the vector of HPV infection to sexual partners but he is rarely considered as a potential final target. HPV-related cancers in men are in fact found among selected people considered at risk for infection such as immunodeficiency patients (due to viruses such as HIV/AIDS or other non-viral causes) and/or homosexuals, overall in developed countries (Giuliano et al. 2007). About 32,000 cases of new cancers in men and women attributable to HPV infection such as cervix, vagina, vulva, penis, oral cavity, head or neck and canal anal, were found in the USA in 2009 (American Cancer Society 2009). HPV types that infect the genital area are categorized in “high-risk” HPV (HR-HPV) and “low-risk” HPV (LR-HPV), and the World Health Organization (WHO) International Agency for Research on Cancer recognizes at least thirteen different types of HR-HPV. Types 16 and 18 are frequently associated with more than 70 % of cervical cancers worldwide, while types 6 and 11 are frequently involved in the majority of cases of anogenital warts (Albrow et al. 2012; Nyitray et al. 2010). The same genotypes responsible for anogenital cancers are often involved in the genesis of head and neck cancers (de Pokomandy et al. 2009). Genital infection is often asymptomatic in both genders although the evidence of sexual warts could be easily found in men than in women. In other rare cases the presence of plain condylomata has been identified through the preventive use of acetic acid solution (Wright 2003). On the other hand, periodical Pap test and subsequent HPV test investigations allow to exert cancer screening visits in women thus reducing the risk of developing cervical cancers and monitoring couples with stable sexual partners. The frequency of HPV infection in various groups of male subjects was analysed in a systematic review of the literature, which included 40 papers published from 1999 to 2006 (Giuliano et al. 2007). The prevalence of HPV in men ranged from 1.3 to 72.9 %, and it is at least 20 in 56 % of the analysed studies (Giuliano et al. 2010). Another review article by Partridge et al. describes a prevalence of HR-HPV infection ranging from 2.3 to 34.8 % of heterosexual males: in these subjects HPV infection has been found also in the anal area with a prevalence of 4.3–15 % independently from their heterosexual condition (Partridge and Koutsky 2006).
14.2 HPV Infection Natural History
14.2.1 Male HPV Infection Natural History
This is a critical point due to the limited information on HPV infection in men and the appropriate criteria of diagnosis to detect the presence of one or more HPV genotypes on the penis or in seminal fluids (Bartoletti et al. 2011). Risk factors could be represented by sexual behaviour, immunodeficiency or HIV co-infection and the evidence of HPV infection in a sexual partner. According to CDC guidelines, each male sexual partner of an infected woman should be accurately evaluated and treated if necessary at least for a period exceeding 3 months which is normally considered as the incubation period necessary to develop visible lesions. The persistence of visible lesion in the male partner could be considered as a determinant factor to induce a possible re-infection in subsequent sexual intercourse (Dunne et al. 2011). Kyo et al. described less prevalence of evident lesions in male partners of infected women but the presence of HPV-DNA in the semen of the same subjects (Kyo et al. 1994). Foresta et al. described HPV viral infection of spermatozoa with possible effects on fertility (Foresta et al. 2011). Penile condylomata represent the most frequent sign of infection in males. Local sense of burning, pain and bleeding are the most frequent subjective symptoms. HPV genotypes 6 and 11 are involved in at least 90 % of infection able to determine genital condylomata. Evident lesions should be adequately treated by N-YAG laser application, diathermo-coagulation, cryo-ablation or medical therapies such as imidazole derivative, podophyllotoxin or trichloroacetic acid (Dunne et al. 2006).
14.2.2 HPV Infection Spontaneous Clearance
The HPV infection prevalence is similar in all classes of age considered although the spontaneous time of infection clearance is usually short. Viral transmission from women to men is possible, but not all male sexual partners of infected women are positive for evident penile condylomata. A possible justification of this phenomenon could be the repeated infections that occurred during sexual activity persisting just for a period of time. Another justification could be represented by the presence of viral undetected infection in men. The mean time to the infection clearance (as the time necessary to determine a complete regression in at least 50 % of infected subjects) has been estimated at 5.9 months (95 % CI 5.7–6.1), while the complete clearance of HPV-DNA in at least 75 % of infected subjects has been estimated at 12 months independently from the HPV genotype considered (Giuliano et al. 2011).
14.3 HPV-Associated Diseases in Men
14.3.1 Male HPV Infection–Related Cancers
HPV-DNA has been frequently found in several cancers in both genders. The cancer sites are strongly related with sexual activity; in particular penile, anal, oral, head and neck (tongue, pharynx, rhinopharynx, hypopharynx, larynx) cancers have been previously described. HPV-DNA has been also recently described in several cases of patients with superficial bladder tumours and benign prostate hyperplasia by Cai et al. (2011).
220.127.116.11 Penile Cancer
Penile cancer afflicts less than 0.5 % of all males with cancer diagnosis in western countries with a cumulative incidence close to 1 out 100,000 inhabitants. The incidence rises to 1.5–3.7 in some South American countries such as Brazil, Perù and Colombia, 2.8 in Uganda and 1.7 in Thailand and India. There is a direct relationship between cervical and penile cancer prevalence according to specific geographical areas. Moreover penile cancer seemed to be less frequent in countries with a large density of circumcised subjects such as Israel, USA, Japan and China (Johnson et al. 2010). HPV-DNA has been found in at least 40–50 % of all penile cancer pathological variants (intra-epithelial neoplasia, squamous–verrucous, basaloid–verrucous) with a prevalence of 16 and 18 genotypes. HPV-DNA has been also found in 75–80 % of penile basaloid intra-epithelial neoplasia (PIN) 1, 2 and 3, but 30–60 % of squamous penile carcinoma represents the most frequent penile cancer pathological variant (Chaux and Cubilla 2012).
18.104.22.168 Anal Cancer
Ninety nine thousand new cases of anal cancer have been estimated in 2002 all around the world. About 40 % of them have been found in men, and 65 % were squamous carcinomas developed from anal intra-epithelial tumours and often related with HPV infection (Cranston et al. 2012). In particular, both 16 and 18 genotypes seemed to be involved in the transformation process. An increased prevalence of 160 % in men and 78 % in women has been described in the USA from 1970 to 2000. This increase is particularly evident among homosexuals and HIV patients. The risk of developing HPV infection with subsequent anal cancer is also related to other factors such as cigarette smoking, anal sexual intercourse and the number of sexual partners (Gao et al. 2010).
22.214.171.124 Head and Neck Cancers
The definition includes all cancers with squamous pathological variant involving the oral cavity, oropharynx, hypopharynx and larynx. 405,000 new cases have been described in 2002 all around the world with 211,000 deaths disease related. The male/female ratio ranged from 2:1 to 15:1. The association with HPV infection is very frequent although some other risk factors such as cigarette or cigar smoking, alcohol consumption or their combination should be considered in each patient. HPV infection prevalence among these cancers is about 60 % in oro-pharynx cancers and 20 % in other head/neck tumours, while the prevalent genotype was HPV 16 (60–80 %). There is a strong relationship between HPV oral infection and oral sex practice (Bisht and Bist 2011).