What is the primary cause of anal cancer?

Primary Cause of 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

HPV Infection and Anal Cancer

• 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 1, 2
• HPV-16 can be detected in approximately 90% of HPV-positive cases of anal squamous cell carcinoma 2
• Squamous cell carcinoma of the anus (SCCA) and its precursor lesion, anal intraepithelial neoplasia (AIN), are mostly attributable to HPV infection 1
• The progression from precursor lesions to invasive cancer typically follows a slow pattern, with progression from AIN 3 to invasive malignancy being uncommon in immunocompetent patients 3

Risk Factors for HPV Persistence and Anal Cancer

• Factors increasing the risk of persistent HPV infection and subsequent malignancy include:
  • Anal intercourse and high lifetime number of sexual partners 1, 4
  • Human immunodeficiency virus (HIV) infection 1, 3
  • Immune suppression in transplant recipients 1
  • Use of immunosuppressants such as long-term corticosteroids 1
  • History of other HPV-related cancers 1
  • Autoimmune disorders 1
  • Cigarette smoking 1, 4
  • Prior history of anogenital warts 1, 4

High-Risk Populations

• Men who have sex with men (MSM) have significantly higher risk of HPV infection and HPV-related disease compared to heterosexual men 5, 4
• 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 3
• The incidence is also higher among HIV-positive women 1

Epidemiology and Trends

• Anal cancer is a rare disease, accounting for 1-2% of digestive tract tumors and 2-4% of anorectal tumors 1, 3
• The annual incidence is approximately 0.5-2.0 per 100,000 people 1, 3
• The incidence of anal cancer in Europe, Australia, and the United States is increasing 1, 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 1

Prevention

• HPV vaccination holds promise for anal cancer prevention for those not already HPV-infected 2, 6
• 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, 6
• Currently, no national recommendations exist for cytologic screening to prevent anal cancers, despite the high risk in certain populations 1, 5

Clinical Implications

• Most early-stage anal cancers are asymptomatic, reflecting the typically slow growth pattern 3
• Common presenting symptoms include bleeding, pain, itching, discharge, and sensation of a rectal mass 1, 3
• Diagnosis is often delayed because bleeding is attributed to hemorrhoids 1
• The median age for diagnosis of anal cancer is 69 years, suggesting a long latency period 3