Anal Cancer in HIV-Infected Individuals

Jessica Wells, PhD, RN

Katherine Yeager, PhD, RN

Once a terminal illness, HIV is now considered a chronic disease due to the advances in highly active antiretroviral treatment (HAART). Today, individuals infected with HIV often manage comorbidities, including cancer, with their HIV disease.¹ During the pre-HAART era, individuals infected with HIV were at significant risk for three types of AIDS-defining cancers—Kaposi’s sarcoma, non-Hodgkin lymphoma, and cervical cancer.

Due to the advancements in treatment and an aging HIV population, HIV-infected individuals are less likely to die from opportunistic infections but now face a growing problem of non—AIDS-defining cancers, particularly Human Papillomavirus (HPV)–related cancers.²

HPV is one of the most common sexually transmitted infections in the United States and includes a group of more than 150 related viruses. There are many subtypes of HPV, but the one most likely to cause anal cancer is HPV-16. HPV-16, as well as HPV-18, HPV-31, HPV-33, HPV-45, and some others are considered high-risk types of HPV because they are strongly linked to cancer.³

These HPV subtypes can also cause cancers of the cervix, vagina, and vulva in women, as well as cancer of the penis in men, and throat cancer in both women and men. HPV is passed from one person to another during skin-to-skin contact with an infected area of the body. Infection with HPV is common, and in most cases the body can clear the infection on its own. But in some people, like those with HIV, the HPV infection does not clear and is persistent. Persistent infection, especially with high-risk HPV types, can eventually cause certain cancers, including anal cancer.⁴

Increased Incidence of Anal Cancer

The increased prevalence and persistence of HPV infections in the HIV-infected population has contributed to increased incidence of anal cancers. Similar to cervical cancer, persistent HPV infection is a significant cause of anal precancerous lesions and anal cancer in HIV-infected individuals.⁵

Immunosuppression plays a significant role in the high prevalence and persistence of HPV infections seen in HIV-infected individuals. Individuals living with HIV not only have an increased risk of acquiring a HPV infection, but also are more likely to have persistent HPV-induced anal squamous intraepithelial lesions.⁵

These lesions can progress to cancer. Among cancer sites associated with HPV infection, anal cancer has the highest incidence rate and occurs at an even greater rate among those infected with HIV than the general population. HIV-infected individuals are 28 times more likely than the general population to be diagnosed with anal cancer. Mortality and morbidity from anal cancer among HIV-infected individuals is also substantial. The 5-year survival rates range from 47% to 60%.⁶

Screening for Anal Cancer

The goal of a cancer screening program is to capture and treat early signs of precancerous lesions before progression to cancer. The success of a national cervical screening program over the last five decades has led to drastic decreases in cervical cancer mortality and morbidity in the general population.¹

Analogous to the cervix, the anal canal has a transformation zone where columnar epithelial cells transition to squamous epithelia. This zone is vulnerable to the development of precancerous lesions from HPV infection.

Anal pap testing involves collecting cells from the anal canal for cytological examination. All abnormal anal pap cytology, regardless of grade, is recommended to be followed up by anoscopy and biopsy of suspected precancerous lesions for histologic confirmation. High resolution anoscopy is important in identifying areas that require treatment in efforts to prevent progression to anal cancer. Unfortunately, research-based screening guidelines for anal cancer are not available.

Jessica Wells, PhD, RN, is working to better understand how to decrease the personal and clinical burden of anal cancer in persons living with HIV. Wells and colleagues conducted an integrated review of recommendations and guidelines for anal cancer screening to provide a guide to inform healthcare clinicians.⁷

This review found that no formal national or international guidelines exist for routine screening of anal cancer for HIV-infected individuals. To date, no randomized control trial has provided strong evidence supporting efficaciousness and effectiveness of an anal cancer screening program. Wells reviewed and synthesized screening recommendations for HIV-infected individuals from seven international, national, and statebased reports. These guidelines based on expert opinion suggest that anal cancer screening may be effective in decreasing the incidence of anal cancer. This review highlights the need for further research to define standard of care for anal cancer screening in HIV-infected persons, a vulnerable group that will benefit from an anal cancer screening program.

Given the heightened incidence in this population, it is imperative that clinicians provide or connect the patient to cancer prevention resources, including HPV vaccination when indicated. From the review of recommended guidelines, it is suggested that all HIV-infected patients should, at a minimum, have a visual inspection and digital rectal exam included in their annual physical exams. Annual or biennial anal pap testing is strongly recommended, especially for those high-risk individuals living with HIV.

These recommendations are given under the assumption that these patients are managed at a high-resource setting where trained and skilled clinicians, cytology, pathology, high resolution anoscopy, biopsy, and necessary treatment are available.

No doubt more research and education are needed to combat anal cancer, especially for those HIV-infected individuals who experience such a high burden of disease. Future efforts must focus on screening studies to provide clear directions for cancer prevention in this population to combat the rising rates of anal cancer.

References

• Darragh TM, Winkler B. Anal cancer and cervical cancer screening: key differences. Cancer Cytopathol. Feb 25 2011;119(1):5-19.
• Shiels M, Cole S, Kirk G, Poole C. A Meta-Analysis of the Incidence of Non-AIDS Cancers in HIV-Infected Individuals. J Acquir Immune Defic Syndr. 2009;52(5):611-622.
• Palefsky JM, Holly EA, Gonzales J, et al. Detection of human papillomavirus DNA in anal intraepithelial neoplasia and anal cancer. Cancer Res. 1991;51(3):1014-1019.
• Ahdieh L, Klein RS, Burk R, et al. Prevalence, incidence, and type-specific persistence of human papillomavirus in human immunodeficiency virus (HIV)-positive and HIV-negative women. J Infect Dis. 2001;184(6):682-690.
• Frisch M, Biggar RJ, Goedert JJ. Human papillomavirus-associated cancers in patients with human immunodeficiency virus infection and acquired immunodeficiency syndrome. J Natl Cancer Inst. 2000;92(18):1500-1510.
• Chiao EY, Giordano TP, Richardson P, El-Serag HB. Human immunodeficiency virus-associated squamous cell cancer of the anus: epidemiology and outcomes in the highly active antiretroviral therapy era. J Clin Oncol. 2008:26(3):474-479.
• Wells JS, Holstad MM, Thomas T, Bruner DW. An integrative review of guidelines for anal cancer screening in HIV-infected persons. AIDS Patient Care STDs. 2014;28(7):350-357.