Anal cancer has been repeatedly linked to sexual activity.  It appears that, like cervical disease, risk for anal cancer is increased in women and men with more lifetime sexual partners.  Frish et al  conducted a case control study that revealed that women with greater than 10 lifetime sexual partners had a 5 fold increase in their risk for anal cancer when compared to women with one lifetime partner.    Intercourse before the age of 20 with greater than 4 partners increased risk three fold when compared to women who had not yet had intercourse at that age.   Female cases were also more likely to have had anal intercourse (odds ratio 2.2) and to have started this behavior before the age of 30 (odds ration 4.4).  2/3 of female cases had a history of anogenital warts; anal warts alone increasing the risk nearly 10 fold (odds ratio 9.8).  The odds ratio was also increased if there was a prior history of STD (odds ratio for gonorrhea of 4.4 and 2.2 for trichomonas).  There was also an increased odds ratio in women with previously diagnosed cervical neoplasia (odds ratio of 2.6)[8].

Men in this same study showed a similar profile.  Interestingly greater than 10 female lifetime sex partners increased the odds ratio to 2.8 when compares to men with 2-3 lifetime partners.  Other STDs, history of receptive anal intercourse, and anal warts also increased the odds of being a male case of anal carcinoma.  In men who had never reported having a heterosexual relationship, the odds ratio increased to 12.7.  [8]

It has been recognized that MSMs are at higher risk for anal cancer even before the dawn of the AIDS epidemic [2].   The incidence is estimated to be approaching 35 cases per 100, 000, about the same incidence as cervical cancer before routine PAP smear screening programs were created[7].  Homosexual men, regardless of HIV serostatus are more likely to have ASIL.  HIV infection increases the risk that that ASIL will be of a higher grade and that if LSIL is found that it will progress to HSIL within two years.  Lower CD4 counts also increased the relative risk of developing HSIL.  Other risk factors for progression of ASIL are presence of more oncogenic strains of HPV in the anal canal and HPV positive serology [7].

It is as of yet unclear what impact HAART will have on anal cancer and dysplasia.  Some postulate that dysplasia may be more likely to regress with increasing CD4 counts.   Others predict that these life-extending meds may lead to more cases of anal cancer as the increasing life expectancy of HIV infected individuals provides time for dysplasia to progress to invasive cancer.

Invasive anal cancer is 6.8 times more common in HIV positive women than their HIV negative counterparts.  HIV positive women are also similarly more likely to have ASIL than their matched HIV negative counterparts.  In one natural-history cohort study of women with high-risk sexual behavior, 26% of HIV positive women compared to 8% of HIV negative women had abnormal anal cytologies.  6% of HIV positive women had HSIL compared to 2 % among HIV negative women.  Abnormal cervical cytology in HIV positive women also increased the risk of abnormal anal cytology (2.2 relative risk)[9].

There is a paucity of information regarding HIV negative women and their ASIL risk related to their cervical cytology.  It is thought, however, that all women with a history of cervical disease are also at increased risk for development of anal cancer [8].  In one prospective cohort study, a history of HPV genital infection increased the relative risk of development of anal cancer by 8 fold.  Though the confidence interval of this relative risk includes one because the number of anal cancer cases reported in this cohort were small, there appears to be an association between cervical disease and anal dysplasia[10].

Smoking has also been identified as a risk factor for anal cancer independent of sexual practices [11].  Alcohol consumption is not cited as a  risk factor in the medical literature on anal cancer.

Another risk factor appears to be chronic pharmacologic immunosupression.  One study looking at patient with renal allografts revealed a 100-fold increase in the incidence of anogenital cancers when compared to the general population [12].  It is unclear if chronic corticosteroids use for other disease processes is a risk factor for anal cancer [11].