Primary Cause and Risk Factors for Anal Cancer

HPV Infection and Anal Cancer

Human papillomavirus (HPV) infection is the primary cause of anal cancer, representing the causative agent in 80-85% of patients, particularly HPV types 16 and 18 1, 2, 3
HPV is associated with approximately 90% of anal squamous cell cancers, making it second only to cervical cancer in the closeness of its association with this virus 4
Squamous cell carcinoma of the anus (SCCA) and its precursor lesion, anal intraepithelial neoplasia (AIN), are mostly attributable to HPV infection 2, 3

Factors increasing the risk of persistent HPV infection and subsequent malignancy include anal intercourse and high lifetime number of sexual partners 1, 2
Human immunodeficiency virus (HIV) infection increases the risk of persistent HPV infection and subsequent malignancy 1, 3
Immune suppression in transplant recipients increases the risk of persistent HPV infection and subsequent malignancy 1, 2
Use of immunosuppressants such as long-term corticosteroids increases the risk of persistent HPV infection and subsequent malignancy 1
History of other HPV-related cancers increases the risk of persistent HPV infection and subsequent malignancy 1, 2
Autoimmune disorders increase the risk of persistent HPV infection and subsequent malignancy 1, 2
Cigarette smoking increases the risk of persistent HPV infection and subsequent malignancy 1, 2

Men who have sex with men (MSM) have significantly higher risk of HPV infection and HPV-related disease compared to heterosexual men 5
The incidence of anal cancer in MSM is approximately 35 per 100,000 1
In HIV-positive MSM, the incidence increases dramatically to 75-135 per 100,000 1
HIV-positive individuals have a 30-fold higher risk of developing anal cancer compared to the general population 6
The incidence is also higher among HIV-positive women 1

Anal cancer is a rare disease, accounting for 1-2% of digestive tract tumors and 2-4% of anorectal tumors 1, 6
The annual incidence is approximately 0.5-2.0 per 100,000 people 2, 6
The incidence of anal cancer in Europe, Australia, and the United States is increasing 2
In the United States, there has been more than a doubling increase in the reported number of new, age-adjusted cases per 100,000 people per year over the last 40 years 2

The quadrivalent HPV vaccine has shown efficacy in preventing 77.5% of high-grade squamous intraepithelial lesions/anal intraepithelial neoplasia secondary to HPV 6, 11, 16, or 18 5
Currently, no national recommendations exist for cytologic screening to prevent anal cancers, despite the high risk in certain populations 4, 5

Most early-stage anal cancers are asymptomatic, reflecting the typically slow growth pattern 6
Common presenting symptoms include bleeding, pain, itching, discharge, and sensation of a rectal mass 2, 6
Diagnosis is often delayed because bleeding is attributed to hemorrhoids 2
The median age for diagnosis of anal cancer is 69 years, suggesting a long latency period 6

Receptive anal sex is an independent risk factor for anal cancer in all individuals, with HPV infection being the causative agent in 80-97% of anal cancers, primarily through HPV-16 and HPV-18 transmission 7, 8, 9
Receptive anal intercourse is a direct route of HPV transmission to the anal canal, establishing the biological mechanism for cancer risk 7, 8
Among men who have sex with men (MSM) without HIV infection, the incidence of anal cancer is approximately 14-35 per 100,000 person-years, compared to approximately 1 per 100,000 in the general population 8

The National Comprehensive Cancer Network recommends that individuals with immunosuppression, such as those with HIV, are at a higher risk of anal cancer, with an incidence of 75-135 per 100,000 person-years 8
The American College of Physicians notes that immunosuppression facilitates persistence of HPV infection, rather than initiating it, with low CD4+ counts appearing most influential 6-7 years prior to anal cancer diagnosis 7, 9

The Centers for Disease Control and Prevention recommends annual digital anorectal examination (DARE) for HIV-positive individuals and for HIV-negative MSM with a history of receptive anal intercourse, with a strength of evidence rated as moderate 10, 11
The American Cancer Society notes that data remain insufficient to recommend routine anal cytology screening, though some centers perform it in high-risk populations 10, 11

The National Comprehensive Cancer Network states that solid organ transplantation increases the incidence of anal cancer to 13.4-29.6 per 100,000 person-years, depending on time since transplant, with a high strength of evidence 7
The European Society for Medical Oncology notes that autoimmune disorders on immunosuppressive therapy also elevate the risk of anal cancer, with a moderate strength of evidence 7, 8