Anal Cancer: Symptoms, Types, Causes and Treatment

Anal cancer is a rare but increasingly common malignancy that affects the tissues of the anus. While it represents a small percentage of all digestive system cancers, its incidence has risen steadily in recent decades, especially in certain high-risk populations. Understanding its symptoms, types, causes, and treatment options is essential for early detection, effective management, and prevention. This article brings together the latest evidence to provide a comprehensive overview of anal cancer, synthesizing information from leading research and clinical guidelines.

Symptoms of Anal Cancer

Recognizing the symptoms of anal cancer is crucial for early diagnosis and improving outcomes. Many signs are subtle or commonly mistaken for benign conditions, which can delay seeking medical help. However, awareness of the typical symptoms can prompt timely evaluation and intervention.

Symptom	Description	Frequency/Significance	Sources
Bleeding	Blood from the anus or rectum	Most common symptom	1 2 3 4
Pain	Anal or perianal discomfort	Very frequent	1 2 3 4
Mass sensation	Feeling of a lump or fullness	Noted in many cases	2 3 4
Weight loss	Unintentional loss of body weight	Associated with advanced disease	1
Foreign body sensation	Feeling something abnormal in anal area	Less common	1
Asymptomatic	No specific symptoms	Up to 20% of cases	2

Table 1: Key Symptoms

Overview of Anal Cancer Symptoms

Anal cancer frequently presents with symptoms that may be easily confused with more benign anorectal disorders, such as hemorrhoids or fissures. The majority of patients report at least one noticeable symptom at diagnosis, and being vigilant to these clues can make a significant difference.

Most Common Presenting Symptoms

• Rectal or Anal Bleeding:
  This is the most frequently reported symptom, observed in up to 78% of patients. It may be intermittent or persistent and can range from small amounts of blood on tissue paper to more obvious bleeding. Because rectal bleeding is also common in benign conditions, it is often overlooked 1 2 3 4.

• Anal/Perianal Pain:
  Persistent pain or discomfort around the anus is another common complaint, present in 63% or more of patients with anal cancer. Pain may worsen during or after bowel movements and can be a sign of more advanced disease 1 2 3.

• Sensation of a Mass or Lump:
  Some people experience the feeling of a mass, fullness, or a foreign body in the anal region. This can be due to the growth of a tumor and is noted in a significant proportion of cases 2 3 4.

• Weight Loss:
  Unintentional weight loss is less common but is often associated with advanced or aggressive disease. Its presence should always prompt further investigation 1.

• Other Symptoms:
  Other less frequent symptoms include changes in bowel habits, itching, discharge, and swollen lymph nodes in the groin.

Asymptomatic Cases

Importantly, up to 20% of people diagnosed with anal cancer may not report any tumor-specific symptoms. This highlights the importance of regular medical checkups, especially for high-risk individuals 2.

Physical Findings on Examination

During a physical examination, nearly all patients have at least one abnormal finding, such as a visible tumor, palpable mass, or pain/bleeding during a digital rectal exam (DRE). Patients with more advanced disease (T3/T4) typically present with more symptoms and more pronounced physical findings than those with early-stage tumors 1.

Types of Anal Cancer

Anal cancer is not a single disease but comprises several distinct types, each with unique characteristics. Understanding these types helps guide appropriate treatment and informs prognosis.

Type	Description	Prevalence	Sources
Squamous Cell Carcinoma (SCC)	Arises from squamous cells lining the anal canal	~80-90% of cases	5 6 7 8 9 14 15
Adenocarcinoma	Originates from glandular tissue	Less common	5 6 7 8
Basaloid/Transitional	Variant of SCC, sometimes classified separately	Rare	6 8 14
Melanoma, Lymphoma, Sarcoma	Other rare histologies	Very rare	6 8 14

Table 2: Main Types of Anal Cancer

Overview of Anal Cancer Types

Anal cancers are classified mainly by the type of cell from which they develop. The most prevalent is squamous cell carcinoma, but rarer forms also exist.

Squamous Cell Carcinoma (SCC)

• Description:
  SCC arises from the squamous epithelial cells lining most of the anal canal and perianal skin.
• Epidemiology:
  Approximately 80-90% of all anal cancers are SCC, making it by far the most common type 5 6 7 8 14 15.
• Association with HPV:
  SCC is strongly linked to infection with high-risk strains of human papillomavirus (HPV), particularly types 16 and 18 6 9 14 15.

Adenocarcinoma

• Description:
  This type arises from glandular cells, either from the anal glands or the rectal mucosa.
• Prevalence:
  Adenocarcinomas account for a small minority of anal cancers and often behave more like rectal cancers in terms of spread and treatment 5 6 7 8.

Other Rare Types

• Basaloid/Transitional Cell Carcinoma:
  These are considered subtypes or variants of SCC and are rare 6 8 14.
• Melanoma, Lymphoma, Sarcoma:
  Malignancies such as melanoma, lymphoma, and sarcoma can also develop in the anal region, but these are extremely rare and require specialized management 6 8 14.

Site-Based Classification

Anal cancers can also be classified by their primary location:

• Anal Canal:
  Between the anorectal junction and the anal verge.
• Perianal Region:
  The skin within 5 centimeters of the anal verge 4 15.

Causes of Anal Cancer

The development of anal cancer is multifactorial, with several established and emerging risk factors. Understanding these causes is essential for prevention and early intervention, especially in high-risk groups.

Cause/Risk Factor	Role/Mechanism	At-Risk Groups/Details	Sources
HPV Infection	High-risk types (esp. 16/18) cause cellular changes	80-90% of SCC cases; MSM, HIV+	6 9 10 11 14 15
Immunosuppression	Reduced immune surveillance	HIV+, transplant recipients	6 9 14 15 16
Cigarette Smoking	Promotes carcinogenesis	Independent risk factor	12 13 14
Sexual Behavior	High number of partners, receptive anal intercourse	MSM, women with many partners	10 11 12 13
History of Genital Neoplasia	Shared HPV etiology	Women with cervical/vulvar cancer	6 9 14
Other STIs (e.g., HSV)	Possible co-factor	Unclear role	12 14

Table 3: Major Causes and Risk Factors

Human Papillomavirus (HPV) Infection

• Central Role:
  HPV infection, particularly with high-risk types 16 and 18, is the single most significant cause of anal cancer, especially for SCC. Over 80% of anal SCCs harbor HPV DNA, with type 16 detected in the vast majority 6 9 10 11 14 15.
• Transmission:
  HPV is sexually transmitted, and certain sexual behaviors (e.g., anal intercourse, multiple sexual partners) increase risk 10 11 13.

Immunosuppression

• HIV Infection:
  Individuals living with HIV, especially men who have sex with men, are at much higher risk due to both increased HPV infection rates and reduced immune control over oncogenic viruses 6 9 14 15 16.
• Transplant Recipients:
  Those taking immunosuppressive drugs after organ transplantation also face elevated risk 6 14 15.

Cigarette Smoking

• Independent Risk:
  Smoking is consistently identified as an independent risk factor for anal cancer, likely due to its carcinogenic effects on mucosal tissues 12 13 14.

Sexual Behavior

• High Sexual Activity:
  Both men and women with a greater number of lifetime sexual partners, early age of first intercourse, and a history of receptive anal intercourse have increased risk 10 11 12 13.
• Men Who Have Sex with Men (MSM):
  MSM, particularly those with HIV, have the highest documented rates of anal cancer 6 9 11.

Other Contributing Factors

• History of Genital Neoplasia:
  Women with a history of cervical or vulvar cancer are more likely to develop anal cancer, likely due to shared HPV infection 6 9 14.
• Other Sexually Transmitted Infections:
  Infections such as herpes simplex virus may play a secondary, less defined role 12 14.
• Chronic Inflammation:
  Unlike some earlier theories, chronic irritation or inflammatory conditions (like hemorrhoids) are not considered major causes 13 14.

Prevention Implications

• HPV Vaccination:
  Vaccination against HPV can prevent the majority of anal SCC cases and is a key preventive strategy 5 7 19.
• Screening:
  Screening high-risk individuals for anal precancerous lesions (HSIL), especially those with HIV, can help catch disease early and reduce cancer development 2 9 16.

Treatment of Anal Cancer

Treatment for anal cancer has evolved significantly, with the goal of curing the cancer while preserving anal function and quality of life. The approach depends on the type and stage of disease, as well as patient-specific factors.

Treatment Modality	Indication	Main Features	Sources
Chemoradiation	Mainstay for most cases (SCC)	5-FU + mitomycin or cisplatin; non-surgical	8 13 15 17 18 19
Surgery	Salvage for non-responders or small early lesions	Abdominoperineal resection or local excision	8 13 15 17
Systemic Chemotherapy	Metastatic or recurrent disease	5-FU + cisplatin; other regimens	8 15 18
Novel Therapies	Advanced/refractory cases, clinical trials	Immunotherapy, targeted agents, vaccines	18 19
Surveillance	All treated patients	Regular follow-up for recurrence	17 19

Table 4: Major Treatment Approaches

Overview of Anal Cancer Treatment

The treatment landscape for anal cancer now favors organ preservation and multimodal therapy. The standard approach is concurrent chemoradiation, a strategy that has dramatically improved outcomes compared to surgery alone.

Chemoradiation: The Mainstay

• What It Involves:
  A combination of radiation therapy and chemotherapy (typically 5-fluorouracil [5-FU] and mitomycin C or cisplatin).
• Benefits:
  This approach leads to complete tumor regression in 80–90% of patients with localized disease, while preserving anal sphincter function and avoiding the need for permanent colostomy 8 13 15 17 18 19.
• Indications:
  Standard for most squamous cell carcinomas of the anus, regardless of stage at diagnosis.

Surgery

• Current Role:
  Surgery is now reserved for select situations:
  • Small, well-defined lesions at the anal margin may be excised locally.
  • Salvage abdominoperineal resection (removal of anus and rectum with permanent colostomy) is used for cases not cured with chemoradiation or for persistent/recurrent disease 8 13 15 17.
• Historical Context:
  Before the 1970s, surgery was the primary treatment, but outcomes and quality of life were poorer.

Systemic Chemotherapy

• In Advanced Disease:
  For patients with metastatic or recurrent anal cancer, systemic chemotherapy (often 5-FU plus cisplatin) is used, sometimes in combination with other drugs 8 15 18.

Novel and Emerging Treatments

• Immunotherapy and Targeted Agents:
  Immune checkpoint inhibitors, HPV-targeted vaccines, and other novel agents are promising and currently being studied in clinical trials 18 19.
• Photodynamic Therapy:
  Experimental for select cases 18.

Surveillance and Follow-Up

• Importance:
  All patients require ongoing follow-up after treatment to detect recurrences early, as additional curative-intent therapy may be possible 17 19.

Multidisciplinary Care

• Team Approach:
  Optimal management requires input from gastroenterologists, oncologists, surgeons, radiologists, and other specialists 15 17.

Special Considerations

• High-Grade Squamous Intraepithelial Lesions (HSIL):
  For high-risk groups, treating HSIL can reduce progression to anal cancer 16.
• HPV Vaccination:
  Prevention remains vital; HPV vaccination can prevent most cases of anal SCC 5 7 19.

Conclusion

Anal cancer is a rare but increasingly common malignancy, primarily caused by HPV infection. Early recognition of symptoms, awareness of risk factors, and advances in treatment have substantially improved outcomes. Here’s what we’ve covered:

• Symptoms:

  • Most common are rectal bleeding, anal pain, mass sensation, and sometimes weight loss.
  • Up to 20% may be asymptomatic.

• Types:

  • Squamous cell carcinoma is the predominant type.
  • Adenocarcinoma and other rare types exist.

• Causes:

  • HPV infection (especially types 16/18) is the main cause.
  • Immunosuppression, smoking, and certain sexual behaviors increase risk.

• Treatment:

  • Chemoradiation is the mainstay, with surgery reserved for select cases.
  • Systemic chemotherapy and novel therapies are options for advanced cases.
  • HPV vaccination and HSIL treatment can help prevent disease.

Staying informed and proactive—through vaccination, regular checkups, and attention to symptoms—can make a significant difference in preventing and successfully treating anal cancer.