Detection of anal dysplasia through anal pap testing in HIV infected individuals

Background:

Anal cancer is infrequent in the general population; currently at the rate of approximately one per 100,000 (Chiao, et al.,2005). However, the incidence of anal cancer in HIV-infected men who have sex with men (MSM) has been increasing at rates of 60-160 per 100,000 (Salit, et al., 2010).

Rates of anal cancer among HIV-infected MSM are comparable to rates of cervical cancer in women prior to the initiation of routine screening for cervical dysplasia. Most of the literature pertainng to HPV disease has focused on cervical abnormalities, but anal infections are actually more common. Several studies have also shown that anal cancer is increasing in HIV-infected individuals with the advent of highly active anti-retroviral therapy, probably because of the prolonged life span due to therapy.

What is Anal Dysplagia? It refers to abnormal structural changes in the cells that can happen to the cells that make up the lining (mucosa) of the anal canal. Similar to cervical dysplasia, it is a pre-cancerous condition where abnormal cells clustered together to form a lesion. Anal dysplasia occurs mainly in two places: in the “junction,” where the anal canal meets the rectum; and in the peri-anal skin, just outside of the anal opening. These cells may then progress from low-grade lesions to high-grade lesions.

What causes Anal Dysplagia? It is most commonly linked to human papillomavirus (HPV), the same virus that causes warts and the most common sexually transmitted disease (Salit, 2010). HPV is a common virus with at least 70 strains, many of which can be transmitted sexually.

 

Under normal circumstances our cells make certain proteins that help prevent dysplasia and cancer. HPV can shut off these proteins, allowing dysplasia to develop. People with HIV, including women, are at increased risk for anal dysplasia. HIV seems to interact with HPV to make these changes more likely. Furthermore, anal dysplasia has been clearly associated with HIV and particularily with a decrease in CD4+ cell count.

Risk factors for Anal Dysplasia:

Individual that are at risk for anal dysplagia include but are not limited to the following:

  • Men and women who have receptive anal intercourse (RAI). Studies show that the rates of anal cancer are much higher in men who have anal sex with men (MSM) and are HIV positive, which leads to up to the next point.
  • HIV infection: those who are HIV+ are especially at risk because they are at higher risk for persistent HPV infection. And unlike other sexually transmitted diseases, condoms are not effective in preventing HPV infection.
  • CD4 count < 200cells/L. Those with a CD4 count lower than 200 have a low immune system and abnormal cell changes can occur with no or little resistance.
  • Individuals with a history of anal warts are at risk of getting anal cancer.
  • Having multiple sex partners increases the likelihood of getting anal HPV.
  • High grade cervical/vulvar dysplasia women with high grade cervica/vulvar dsyplasia have a higher chance.
  • Lastly, cigarette smoking is another risk factor for anal dysplasia.

Having said all this there is no consensus on who should get an anal pap smear. Some recommend that all men and women who have RAI should have an anal pap smear performed regularly. Some recommend it for all MSM, for all individuals with HIV and anal warts, or for all individuals with a history of anal warts.

What is anal pap testing? It is the anal counterpart of the cervical pap smear. It is a test to screen for anal dysplasia, used for the early detection of anal cancer. Usually a sample of cells is collected from the anal canal and are then examined under the microscope to identify anal dysplasia. Pap tests of the anal canal are simple to perform, clinically effective, and cost-effective to reduce the incidence of invasive disease in high-risk individuals.

Anal pap test results:

There are 5 possible results from the pap test:

  1. Negative/Normal
  2. ASCUS (Atypical Squamous Cells of Unknown Significance) cells are abnormal, but no definite diagnosis can be made.
  3. LSIL (Low-grade Squamous Intraepithelial Lesion) means mild dysplasia.
  4. HSIL (High-grade Squamous Intraepithelial Lesion) means moderate to severe dysplasia
  5. Anal Cancer (Squamous Cell Carcinoma)

 

Follow-up from an anal pap test:

If a result is normal, the suggestion is to follow up with routine screening. When the result is abnormal, the patient will be referred for further investigation. The patient might be referred to a colorectal surgeon, an infectious disease doctor, or a physician trained in colposcopy, examination, or biopsy of this region. At a minimum, a digital rectal exam is performed. A proctoscopic exam might follow. Ultimately, a biopsy might be performed, with or without the aid of a colposcope, a dermatoscope, or a high resolution anoscopy (HRA). HRA uses a magnifier to provide more detailed images of the mucosa. During the procedure, lesions are enhanced by first applying a thin layer of dilute vinegar to the mucosa.

Screening guidelines:

At present, there are no standardized policy about anal dysplasia screening (e.g. who and how often). Anal paps are not included into the therapeutic guidelines set out by the BC Center for Excellence for HIV treatment and care. Furthermore, there are no universally accepted guidelines. This is in part due to the fact that there has not been enough studies conducted on the needs even though it is statistically shown that there are significant incidences of anal cancer. Thus, there is a need for anal cancer screening. Also, the population at focus is MSM which is not a large enough population to have a significant evidence based studies to create a standard practice.There currently are only a handful of clinics throughout BC and Canada that are conducting screenings. These clinics have an anal dysplasia clinic for which patients are referred to for appropriate follow-up.

Recommendation for anal dysplasia screening:

The recommendations for pap screenings are similar to cervical pap screenings:

  • Initial evaluation of HIV+ patients who are at risk as listed before.
  • If initial pap is normal, then repeat the screening in 6 months.
  • If initial 2 pap smears are normal, repeat yearly. If the CD4<500 cells/L, then to consider screening more often.
  • If pap smears results are abnormal, the patient is referred for further investigations. As mentioned, usually to an anal dysplasia clinic that is able to do HRA and biopsy.

 

Limitations of anal dysplasia screening:

There are limitations of the screening. These include but are not limited to the following:

  • Anal cytology have high sensitivity but low specificity for detecting AIN (anal intraepithelial neoplasia).
  • Grades of dysplasia determined by cytology do not always correlate with grades obtained via biopsy of suspected lesions (i.e. LSIL on cytology is often revealed as HSIL on biopsy).
  • Anal cytology often under represents grade of disease.
  • Therefore, following abnormal PAP smear results to detect for HSIL is improved by direct visualization via HRA and biopsy.

 

Conclusion:

There is a specific population of HIV-infected individuals that are at risk of anal cancer. It is evident that these individuals need special focus on screening for anal dysplasia. By bringing this attention to healthcare providers who work with this population, this can aid in the early detection of a potentially fatal condition. Healthcare workers can take a pro-active approach by providing education to their clients who are at risk. Individuals from a high risk population include MSM, men with bisexual orientation engaging in RAI, women engaging in RAI, patients with persistent anal infection with multiple high risk HPV subtypes. Healthcare workers can also bridge partnership with community health clinics that offer anal pap testing to refer their clients. As awareness and education around anal dysplasia is growing, the hope is to create a standard practice to prevent anal cancer among the HIV-infected people who are at risk.

 

References:

Chiao E. Y., Krown S. E. , Stier E. A. , & Schrag D. (2005). A population-based analysis of temporal trends in the incidence of squamous anal canal cancer in relation to the HIV epidemic. J Acquir Immune Defic Syndr, 40, 451-455.

Salit, I. E., Lytwyn A., Raboud J., Sano M., Chong S., Diong C., Chapman W., Mahony J. B., & Tinmouth J. (2010). The Role of Cytoloy (Pap Tests) and Human Papillovavirus Testing in Anal Cancer Screening. AIDS, 24(9), 1307-1313.

Salit, I. (2010). Fact Sheets: Anal dysplasia. Retrieved October 13, 2010 from http://www.catie.ca/facts.nsf/d3d652aa551a843685256f0900686f9f/

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Written by: Nancy Chow, RN, BScN

Immunodeficiency Clinic, Burrard Building, St.Paul’s Hospital, 1081 Burrard Street, Vancouver, BC V6Z 1Y6

(T) 604-806-9303 (F) 604-806-9311 |  nchow@providencehealth.bc.ca

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