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HPV-Related Diseases in HIV-Infected Individuals (18HH01)

Debra Chew, MD, MPH, Clinical Assistant Professor, Division of Infectious Diseases, Department of Medicine, Rutgers New Jersey Medical School, Lisa Dever, MD, Vice Chair for Faculty Development in the Department of Medicine, Clinical Chief of Infectious Diseases and the Director of the Infectious Disease Fellows, Rutgers New Jersey Medical School, and Shobha Swaminathan, MD, Assistant Professor, Division of Infectious Diseases, Department of Medicine, Rutgers New Jersey Medical School

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Screening for Anal Neoplasia

National guidelines on anal cancer screening are currently lacking. Given the high risk of invasive anal cancer among HIV-infected men and women, some experts have adopted routine anal screening as a standard intervention in HIV primary care. The approach of anal cancer screening is similar to cervical cancer testing with the goal of identifying precancerous areas that can be ablated to prevent invasive anal cancer. Like cervical screening, anal cytologic examination is the first step, followed by confirmation of the disease stage by high-resolution anoscopy and biopsy. Screening is advised, however, only if there is an infrastructure in place for ready access to high-resolution anoscopy and treatment.

Screening for AIN should begin with documentation of any history of anogenital warts, anal receptive intercourse, prior cervical or anal squamous intraepithelial lesions, and other sexually transmitted diseases. Symptoms, such as discharge, pain, bleeding, itching, or spotting after intercourse, should be elicited from patients.

Anal cytologic screening with Pap smear may be easily performed, using a Dacron swab moistened with ordinary tap water with the patient in fetal position. The swab should be inserted as far into the anal canal as far as it will comfortably go, to a maximum of 5 cm, and withdrawn slowly while rotated in a spiral fashion. The swab is then swirled in a liquid cytology vial to release cells into the liquid (liquid should change from clear to slightly cloudy). Anal Pap smear should be followed by a digital rectal exam to palpate for nodules, condylomas or abnormal anal skin (e.g., rough or irregular). A thorough examination of the perianal area and genitalia should be performed. High-grade AIN typically appears as grayish, hyperpigmented patches on the perianal area. Any abnormalities on cytology (ASCUS, low-grade, or high-grade dysplasia) should prompt further evaluation with high resolution anoscopy and biopsy.49,76

Similar to cervical colposcopy, high resolution anoscopy identifies possible high-grade AIN and condylomas. A lubricated anoscope is inserted into the anus, and a cotton swab wrapped in gauze and soaked in 3% acetic acid is inserted through the anoscope. The acetic acid reacts with the skin and allows visualization of dysplastic epithelium by turning it white, referred to as “acetowhite”. Areas suspicious for high-grade AIN, such as those with acetowhitening, or areas showing abnormal vascular patterns, or changes induced by applying Lugol’s iodine (dysplastic lesions appear mustard or light yellow instead of mahogany color) should be biopsied.76

An anal screening protocol for HIV-infected patients has been proposed by Chin-Hong and Palefsky. They recommend that HIV-infected patients with normal anal cytologic results be screened with an anal Pap annually. Those with any abnormal anal cytologic results (ASCUS or higher grade of dysplasia) should undergo high resolution anoscopy with biopsy. Patients’ whose high resolution anoscopy with biopsy show either no lesion or AIN1 (low-grade SIL) may be followed-up every 6 months, whereas those with high-grade SIL or severe dysplasia or carcinoma in situ should be treated and have repeat anoscopy every 4-6 months.76

Treatment of Anal Neoplasia

While optimal approach to treatment of AIN has not yet been defined, many experts treat patients with high-grade AIN. Treatment for those with low-grade AIN is optional but may reduce risk of further enlargement or progression to high-grade AIN or reduce AIN-associated symptoms and patient anxiety. The choice of treatment depends on the size of the lesion and the location of the lesion (perianal vs intra-anal). Although treatment with a variety of approaches may result in complete regression, recurrences are frequent with all treatment modalities in HIV-infected individuals, and often require multiple treatments and close post-treatment follow-up.77-79 The quality of the high resolution anoscopy in detecting and treating all high-grade lesions is key to minimizing disease recurrence.

New treatment options are emerging for the treatment of high-grade AIN. Ablative therapy with infrared coagulation (applying 1.5 second pulse of irradiation in the infrared red directly to dysplastic skin to a depth of approximately 1.5 mm) or electrocautery/hyfrecation offers office-based treatment for high-grade SIL that is effective and well-tolerated.77,80 For individual intra-anal lesions that are small and that represent less than 50% of the circumference of the anal transformation zone, therapy is suggested with either ablation or provider-applied 80% trichloroacetic acid (particularly if lesions are less than 1cm2 at the base). Therapy options for larger intra-anal lesions are either ablation with infrared coagulation or electrocautery/hyfrecation. Alternatively, patient-applied topical 3% or 5% imiquimod (applied 3 times per week) or 5% fluorouracil (4 cycles applied twice daily for 5 days followed by 9 days off) may be used in a staged, step-wise manner to reduce lesion size followed by ablation methods.79

None of the current approaches for high-grade AIN are FDA approved, and data on efficacy to reduce or clear high-grade AIN are very limited. In the only randomized trial comparing treatment modalities in men with AIN treated with imiquimod, topical fluorouracil or electrocautery, complete response rates were 24%, 17%, and 39%, respectively. Recurrences were common, with cumulative recurrence rates of 71%, 58%, and 68% respectively by 72 weeks.81 Ablative therapies are generally well-tolerated and possible complications include mild to moderate post-procedural pain and bleeding for up to 2 weeks; rare complications (<1%) include infection of the treated area and severe bleeding.77,80-81 A phase III National Institutes of Health trial by the AIDS Malignancy Consortium, the ANCHOR trial, is currently underway to assess not only effectiveness of treatment for high-grade AIN but also whether topical or ablative treatment for high-grade AIN compared to active monitoring through regular examinations is ultimately effective in preventing subsequent development of anal cancer.82

The most commonly used treatment for invasive anal cancer is combination radiation and chemotherapy. Treatment is similar in HIV-infected and HIV-uninfected individuals.


 
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