Epidemiology and Clinical Manifestations
Ramírez-Fort MK, Khan F, Rady PL, Tyring SK (eds): Human Papillomavirus: Bench to Bedside.
Curr Probl Dermatol. Basel, Karger, 2014, vol 45, pp 75-91 (DOI: 10.1159/000358370)
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The Epidemiology of Human Papillomaviruses
Alan G. Nyitraya · Michelle R. Iannaconeb
a Center for Infectious Diseases, University of Texas School of Public Health at Houston, Houston, Tex., USA; b Cancer and Population Studies Group, QIMR Berghofer Medical Research Institute, Brisbane, Qld., Australia
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Abstract
Epidemiological studies indicate that most men and women will acquire a sexually transmitted anogenital human papillomavirus (HPV) infection in their lifetimes. In addition, infection with cutaneous HPV types is essentially ubiquitous. Most HPV infections are transient with no clinical symptoms although a minority of infections result in clinical disease such as warts or malignancies. Anogenital warts are the most common clinical manifestation of HPV infection with a prevalence of perhaps 1%. Virtually 100% of cervical cancers, 90-93% of anal canal cancers, 12-63% of oropharyngeal cancers, 36-40% of penile cancers, 40-64% of vaginal cancers and 40-51% of vulvar cancers are attributable to HPV infection. Of the estimated 12.7 million cancers occurring globally in 2008, 610,000 (approx. 5%) were HPV-associated anogenital or oral cancers. Cutaneous HPV types may increase the risk for nonmelanoma skin cancers. Sexual behavior is a primary risk factor associated with anogenital and oral HPV infection among men and women.
© 2014 S. Karger AG, Basel
In 2010, a total of at least 150 different human papillomavirus (HPV) genotypes had been fully described [1] . HPV is somewhat tissue specific with approximately 40 types from the α-genus known to infect the anogenital region and oral cavity. In addition, cutaneous HPV types of the β-genus are responsible for warts commonly found on the hands or feet [2] . While little is known about the natural history of cutaneous HPV infections, these types have also been found on the genitals [3], and anogenital types have been found on the hands [4, 5] . Anogenital HPV is primarily transmitted through vaginal, anal and oral intercourse [5-8] ; however, there is some evidence for hand carriage transmission [4, 5, 9] . Regardless of the transmission route, a large majority of adult men and women in the USA will acquire α-genus-associated HPV infection at least once [10], and infection with β-genus cutaneous types will occur in even more [11].
Anogenital HPV types are classified according to their carcinogenic potential with 13 genotypes considered most oncogenic (i.e. 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68) [12] . It is the necessary cause of cervical cancer [13] and the primary cause of anal cancer [14, 15] . HPV is also commonly found in malignant tumors of the penis, vagina, vulva and oropharynx [16] . In addition to cancer and warts, other HPV-associated outcomes that are important clinically are actinic keratosis and recurrent respiratory papillomatosis.
Epidemiology
Genital Infection and Associated Factors
α-Genus HPV is common although estimates vary by study depending on population, age, what anatomical site is sampled, specimen collection technique and laboratory diagnostic tool. Among 1,921 adolescent and adult women in the National Health and Nutrition Examination Survey in the USA, the cervicovaginal prevalence for ≥ 1 of 37 HPV types was 26.8% [17] . In a meta-analysis of 78 studies conducted on 6 continents, global cervical HPV prevalence was estimated at 10.4% in asymptomatic women with prevalence varying from a high of 31.6% in eastern Africa to a low of 6.2% in southeastern Asia. HPV types 16, 18, 31, 58 and 52 are the most common genotypes [18] . The meta-analysis also observed on all continents except Asia a U-shaped prevalence curve with prevalence peaking in women less than 34 years of age, declining between the ages of 35 and 44, and then increasing in women 45 and older. In Asia, prevalence continued to decline throughout the lifespan after a peak prevalence in women under 34 [18] . Studies among women who have sex with women indicate HPV prevalence may be comparable to that of heterosexual women [19]; however, HPV prevalence can be much higher. A study among 645 sexually active inner city young women observed a cervical HPV prevalence of 54% [20].
Oncogenic types may be acquired most often with an annual incidence of approximately 5-15% [21] . HPV-16 tends to be the most commonly acquired genotype with an estimated incidence of 5.9 (95% confidence interval, CI, 5.2-6.6) per 100 person-years [22] ; however, most infections clear within a few months or few years [23] . In a population of women with cytological abnormalities at the cervix, approximately 90% of prevalent infections cleared within 2 years [24] . HPV that is not cleared by the body is said to be persistent - a crucial step in the development of anogenital cancers [25, 26] . About 5% of women with incident infection will still be infected with the same genotype up to several years later [27] . Persistent oncogenic HPV infection is necessary for the development of precancerous lesions that, in turn, increase the risk for invasive cancer.
Sexual behavior, particularly vaginal sex, is strongly associated with prevalent and incident cervical HPV among women [28, 29] . In addition, age, genetics, use of barrier contraceptives and coinfections may impact genital HPV risk [6, 30-33]. Cigarette smoking, HPV viral load, sexually transmitted infections like Chlamydia tracho-matis and immune incompetence in persons with human immunodeficiency virus (HIV) infection or iatrogenic immunosuppression may increase the duration or persistence of oncogenic HPV infection [21, 34-36].
In general, genital HPV prevalence among healthy men appears to be as high, or higher, than that among women and estimated to range from 1.3 to 72.9% [37]. As with studies among women, prevalence varies by population studied, anatomical sites sampled and HPV DNA detection methods. In recent reports from an ongoing multinational prospective cohort study, 50.5% of men were positive at enrollment for at least 1 known oncogenic or nononcogenic HPV type. HPV-16 was the most common type detected (6.5%) [38] . In this same cohort, overall genital HPV prevalence was similar for both heterosexual men and men who have sex with men (MSMs) but somewhat higher among men who have sex with both women and men [39].
The rate at which heterosexual men acquire a new genital HPV infection is similar to rates reported in young women. In a study among US men, the 12-month cumulative risk of acquiring a new genital HPV infection was 29.2% [40], similar to estimates reported for young males attending a US university [4] and young US females [41]. Unlike observations among women, there is no age-specific pattern of HPV acquisition in men [40, 42].
Studies with repeated interval follow-up of men suggest that the duration of genital infections in men may be similar to that of women [40] . In a large multinational study of genital HPV infection in mostly heterosexual men, the median time to clearance of any type HPV infection was 7.5 months and was significantly longer among younger men [42] while the median time to clearance was longest for HPV-16 at 12.2 months, and was independent of age.
Anal Infection and Associated Factors
Anal HPV infection is a common condition among women and men although most studies have targeted women, MSMs and persons with HIV. Nevertheless, studies indicate that anal HPV infection is also common among heterosexual men [43], including those who report no receptive anal sex [44].
The prevalence of anal and cervical HPV infection among women may be comparable [45] . For example, one large study observed a 27% HPV prevalence at the anal canal and 29% at the cervix among women attending health clinics in Hawaii [46] whi...