Before addressing risk factors, one needs to understand what the term
anal cancer comprises. Tumors that arise from the transitional or squamous mucosa of the anus are termed squamous cell carcinoma (SCC). These terms,
anal cancer and
SCC, are used interchangeably in most studies
3 and will be used interchangeably in the present review as well. Other cancers are also categorized as anal cancers because of their location; these include cloacogenic carcinomas (subset of SCC), developing in the transitional zone; adenocarcinomas, arising mostly from the rectum; basal cell carcinomas, derived from the skin in the perianal area; and malignant melanoma, developing from the skin or anal lining.
3
Not all HPV types have been associated with dyplasia. According to the CDC, oncogenic HPV types are believed to be the causative agent in up to 90% of anal cancers.
14 Persistent HPV infection with any of these 13 high-risk types (ie, oncogenic HPV strains 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 66) is the cofactor leading to the dysplastic changes of AIN seen before anal invasive carcinoma is diagnosed.
2 As with cervical cancer, HPV is the principal cause of anal cancer.
10 A minority of anal cancer cases have not been shown to have a connection with any HPV infection, and no discernible differences have been noted between these cancers and HPV-associated cancers in terms of patient age, adjacent dysplasia, ductal differentiation, or prognosis.
15
Anal HPV infection was present in 24.8% of immunocompetent heterosexual men in a recent study.
2 These infections have been transient, with a low incidence of persistent infection. Immunosuppressed patients, such as transplant recipients and patients with HIV infection, have opposite results, with higher rates of persistent HPV infection, and these persistent infections lead to a higher incidence of HPV-associated malignancies.
16
The prevalence of HPV infection is highest in MSM, HIV-infected men, and transplant recipients, all of whom are in the at-risk population. Even HIV-infected men without a history of anal intercourse have a higher risk of AIN than do the general population.
Most of the research data on HPV and anal cancer in men have been collected in HIV-positive men, especially MSM assumed to be anal receptive. In HIV-negative MSM, the identifiable risk factors for anal cancer include HPV infection, a greater number of HPV types present, the number of receptive anal sex partners, and injection drug use.
17 No association has been seen between age and AIN prevalence in HIV-negative MSM.
17
In the general population, other risk factors for anal cancer include a history of anal intercourse, a history of perianal condylomas, chronic immunosuppression (seen in patients taking immunosuppressive medications, those who are HIV positive, or those who have received organ transplants), age older than 50 years, multiple sexual partners (increasing the risk of HPV infection), and smoking (increasing the risk of non-clearing HPV infection).
3,18 In one study, cigarette smoking and lifetime number of sexual partners were associated with an increased prevalence of anal cancer.
19
Receptive anal intercourse is the most prominent risk factor for anal HPV infection, but infection can also be acquired from contact with other infected genital areas, particularly the vulva in women and the penis in men. Contact of fingers and sex toys with infected fluids may also be associated with anal HPV infection.
18
When interviewing a patient, the physician should always ask about the patient's sexual history, especially when the examination involves the anogenital area. When the examination involves the anal area, the physician should ask questions to discern whether objects, fingers, or other body parts have been inserted into the anus. This type of questioning is appropriate because it provides information relevant to the patient's health. The history should also identify MSM who may practice anal receptive intercourse; such patients must be educated about potential risk factors for acquiring HPV infection amongst other infections.
In heterosexual patients, the causes of anal HPV infection may not be as obvious. In all men, the incidence of HPV infection has increased nearly 3-fold in the past 30 years.
2 The prevalence of anal HPV infection in heterosexual men without a history of anal or oral sex with a man has been shown to be 24.8%; 33.3% of these infections are with oncogenic HPV types. Therefore, anal HPV infection in heterosexual men, even those without any visible or palpable signs of anal condylomas or masses—which are usually caused by nononcogenic, high-risk, HPV types
20—could be considered common. Risk factors for heterosexual men include a large lifetime number of female sex partners and a high frequency of sexual intercourse just before diagnosis. A possible association with lack of circumcision has also been seen.
2
Other possible risk factors related to sexual behavior include self-initiated or partner-initiated anal massage with an object, anal massage or insertion with a finger, nonpenetrating sex (finger-vulvar, penile-vulvar, and oral-penile contact associated with female genital HPV infection), and oral-anal sex.
2 Nonsexual behavioral risk factors include hand carriage, as in hygiene care, from the genitals to the anus
21 and transference from objects of any kind used to manage genital HPV infection.
22