Anal Dysplasia: Symptoms, Types, Causes and Treatment

Anal dysplasia is an increasingly recognized clinical concern that encompasses a spectrum of precancerous changes in the epithelial lining of the anal canal. While often silent and asymptomatic, its progression can lead to anal squamous cell carcinoma, a malignancy whose incidence is rising, especially among certain high-risk groups. Understanding the symptoms, types, causes, and available treatments for anal dysplasia is crucial for both patients and healthcare providers aiming to prevent cancer and manage this condition effectively. Below, we explore these aspects in detail, synthesizing the latest research and clinical insights.

Symptoms of Anal Dysplasia

One of the most challenging aspects of anal dysplasia is its frequently silent nature. The majority of individuals with anal dysplasia do not experience noticeable symptoms, making early detection difficult without targeted screening. In a prospective study of high-risk patients undergoing high-resolution anoscopy (HRA), nearly 69% were found to be entirely asymptomatic, despite the presence of dysplasia on biopsy 1. This underscores the importance of routine screening in populations at elevated risk.

When symptoms do occur, they are often non-specific and may mimic those of other anorectal conditions. Reported symptoms include:

• Anal pain: Present in about 12% of patients with dysplasia, and shown to be independently associated with high-grade disease. Patients experiencing anal pain were significantly more likely to have high-grade dysplasia compared to those without pain 1.
• Rectal bleeding: Noted in about 15% of cases, rectal bleeding can be intermittent or persistent and may be mistaken for hemorrhoidal bleeding 1.
• Pruritus (itching): Experienced by approximately 11%, pruritus is another non-specific symptom that may prompt further investigation 1.
• Visible or palpable anal lesions: Physical examination may reveal lesions or abnormalities, which are more frequently seen in individuals with either low- or high-grade dysplasia compared to those without dysplasia 1.

In some congenital forms, such as anal sphincter dysplasia, the symptoms are more related to defecation disorders—chronic constipation, severe straining, encopresis (fecal soiling), and paradoxical diarrhea with fecal incontinence—resulting from anatomical malformations of the anal canal and sphincter complex 2.

Despite these possible symptoms, the “silent” nature of anal dysplasia remains a major clinical challenge. Therefore, the absence of symptoms does not rule out the disease, particularly in individuals at higher risk, who may benefit from routine screening and anoscopic evaluation 1.

Types of Anal Dysplasia

Anal dysplasia encompasses a spectrum of histopathological changes, ranging from mild atypia to severe dysplastic changes that precede invasive cancer. The two main contexts in which anal dysplasia is described are:

1. Anal Intraepithelial Neoplasia (AIN)

AIN is the most commonly used term for dysplastic changes in the squamous epithelium of the anal canal. It is classified according to the degree of cellular atypia:

• AIN I (Low-grade dysplasia): Represents mild dysplasia, involving the lower third of the epithelium. These lesions are often associated with low-risk HPV types and have a lower risk of progression to cancer 3.
• AIN II (Intermediate-grade dysplasia): Involves moderate dysplasia, affecting up to two-thirds of the epithelial thickness. The risk of progression is intermediate, and the viral genotype present may influence management decisions 3.
• AIN III (High-grade dysplasia): Indicates severe dysplasia or carcinoma in situ, involving more than two-thirds of the epithelium. High-grade lesions are considered the direct precursors to anal squamous cell carcinoma and warrant aggressive management 3 4 5.

2. Congenital Anal Sphincter Dysplasia

Distinct from the HPV-associated neoplastic process, congenital anal sphincter dysplasia is a rare, often familial malformation characterized by improper positioning or fixation of the sphincter complex. This anomaly manifests primarily with chronic defecation disorders rather than neoplastic transformation and may require surgical correction 2.

3. Anal Condylomata and Other Lesions

Anal condylomas (warts), caused by HPV infection, may harbor dysplastic changes. These condylomas can be associated with either low- or high-grade dysplasia, increasing the risk of progression to anal squamous cell carcinoma, particularly in immunocompromised individuals 6.

4. Progression and Recurrence

High-grade anal dysplasia, especially in at-risk populations such as HIV-positive men who have sex with men, has a notably high recurrence rate even after treatment, necessitating ongoing surveillance 8 9.

The classification of anal dysplasia is vital, as it guides management strategies and helps stratify patients by risk of progression to invasive cancer.

Causes of Anal Dysplasia

The development of anal dysplasia is multifactorial, with overwhelming evidence implicating infection by oncogenic (high-risk) types of human papillomavirus (HPV) as the primary etiological agent.

1. Human Papillomavirus (HPV) Infection

HPV is the leading cause of anal dysplasia and anal squamous cell carcinoma. More than 70 HPV subtypes exist, with approximately 35 types specific to the anogenital epithelium. Of these, high-risk subtypes, particularly HPV 16 and 18, are most strongly associated with high-grade dysplasias and progression to cancer 3 4 5 6. In surgical specimens, high-risk HPV was detected in up to 88% of high-grade lesions, with type 16 present in 68% of such cases 3.

The risk of developing anal dysplasia is particularly pronounced in certain populations, including:

• Men who have sex with men (MSM)
• HIV-positive individuals and other immunocompromised patients
• Women with a history of cervical, vaginal, or vulvar cancer These groups show a higher prevalence of persistent HPV infection and are more likely to develop high-grade anal dysplasia 4 5 10.

2. Immunosuppression

Immunocompromised individuals, such as those infected with HIV, have an increased risk for both acquiring and failing to clear oncogenic HPV infections. This leads to higher rates of dysplasia and progression to cancer. Studies show that recurrence rates of high-grade lesions are higher in HIV-infected patients, and the number of lesions treated also increases recurrence risk 8 9. Use of antiretroviral therapy (ART) in HIV-positive individuals confers a protective effect, decreasing the incidence of high-grade dysplasia 10.

3. Other Risk Factors and Genetic Causes

• Anal/genital condylomas: The presence of warts is a predictor of ≥AIN2 lesions 10.
• Specific HPV genotypes: Certain types, such as HPV68, have been identified as significant risk factors for high-grade lesions 10.
• Congenital factors: Rarely, anal dysplasia can be due to congenital malformations, such as anal sphincter dysplasia, which has an autosomal dominant inheritance pattern with variable expression 2.

4. Behavioral and Epidemiological Factors

• Number of sexual partners
• Receptive anal intercourse
• Smoking These factors can increase the risk of acquiring HPV and developing dysplasia 4 5.

Understanding these causes not only aids in identifying at-risk individuals but also informs prevention strategies, such as HPV vaccination and targeted screening.

Treatment of Anal Dysplasia

Treatment strategies for anal dysplasia are determined by the grade of dysplasia, the extent and number of lesions, patient comorbidities, and risk factors for recurrence. The overarching goal is to prevent progression to anal squamous cell carcinoma while minimizing morbidity from treatment.

1. Ablative Therapies

For high-grade lesions (AIN III or HGAIN), ablation is the mainstay of therapy. Techniques include:

• Laser ablation
• Infrared coagulation (IRC)
• Electrocautery These methods can be performed under local anesthesia in an outpatient setting and are relatively well tolerated. High-resolution anoscopy (HRA) is used to guide these procedures, ensuring precise targeting of dysplastic areas 8 9 11. Although effective, recurrence rates remain high—up to 77% in HIV-positive patients and 66% in HIV-negative patients at 3 years post-treatment, warranting close follow-up and repeat treatments as needed 8. IRC has shown efficacy in about 64% of treated lesions, particularly in HIV-positive MSM 9.

2. Excisional Surgery

For small, unifocal lesions, traditional surgical excision with clear margins remains an effective approach. However, extensive or multifocal disease increases the risk of recurrence and postoperative complications, such as anal stenosis and fecal incontinence. This has led to a preference for less invasive ablative techniques, particularly in patients with widespread disease 11.

3. Topical Therapies

Topical treatments, such as 5-fluorouracil and imiquimod, offer a non-surgical option, particularly suitable for multifocal or extensive disease. These agents can be effective but require extended courses and are associated with symptomatic inflammatory responses, which may affect patient adherence 11.

4. Experimental and Immunologic Therapies

Immunotherapeutic approaches, including therapeutic vaccines targeting HPV epitopes (e.g., HPV-16 E7 protein), have shown promise in early-phase trials, producing histological responses and boosting immune reactivity against HPV. While still investigational, these strategies hold potential for future management, especially in patients with persistent or recurrent high-grade lesions 7.

5. Treatment of Congenital Anal Sphincter Dysplasia

For congenital malformations, surgical correction such as posterior butterfly anoplasty combined with fixation of the sphincter to the coccyx has been shown to improve defecation disorders 2.

6. Role of Antiretroviral Therapy

In HIV-positive individuals, ART has a protective effect against the development and progression of anal dysplasia, highlighting the importance of optimal HIV management as part of dysplasia prevention and treatment strategies 10.

7. Surveillance and Recurrence Management

Given the high recurrence rates, particularly in immunocompromised individuals, ongoing surveillance with regular anoscopic evaluation and prompt retreatment of recurrent lesions is essential 8 11. The probability of developing invasive cancer post-ablation remains low (about 2% at 3 years), but vigilance is critical 8.

Conclusion

Anal dysplasia represents a silent yet potentially serious threat, especially for individuals in high-risk groups. Its often asymptomatic nature highlights the need for proactive screening and surveillance. The primary driver of anal dysplasia is persistent infection with high-risk HPV types, although congenital and immunological factors also play roles in certain cases. Classification into low- and high-grade lesions guides clinical management, which includes a range of ablative, surgical, topical, and emerging immunotherapeutic options. Despite advancements, high recurrence rates demand long-term follow-up and patient education. Prevention strategies—including HPV vaccination, safe sexual practices, and optimal HIV management—are pivotal in reducing the burden of disease. As research advances, the hope is for more effective, less burdensome treatments and perhaps universal screening protocols that can further reduce the risk of progression to anal cancer.