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Cervical Lesions in Women With HIV May Point to Developing Anal Cancer

November 2015

HIV-positive women who had precancerous cervical lesions (damaged tissue) in the past had a 4-fold higher chance of precancerous anal lesions in a large French study.1 Human papillomavirus (HPV) infection can cause both cervical and anal lesions, but HIV-positive women are not always checked for anal lesions. Results of this study suggest that women with HPV-related cervical disease should be assessed for anal cancer.

Much research has focused on high rates of anal cancer and anal HPV among HIV-positive gay and bisexual men. Less work has analyzed anal cancer rates and risk factors in HIV-positive women, even though anal cancer rates are rising in both women and men in the general population.2

HPV is the most common sexually transmitted infection in the United States and many other countries. It can cause both anal cancer and cervical cancer, and cervical cancer -- an AIDS cancer -- poses a particular threat to women with HIV. So it seems reasonable that women with HPV-related cervical disease may run a higher risk of anal cancer or the anal lesions that lead to anal cancer. In fact, a U.S. study found HPV more often in the anus than in the cervix of women with HIV.3

Regularly checking for cervical lesions (with a Pap test) and treating any lesions found has greatly lowered the cervical cancer death rate.4 But health authorities in the United States and Europe do not yet recommend regular checking for anal lesions and anal cancer in women or men with HIV infection. To measure rates of anal HPV infection and precancerous anal lesions in women with HIV, a team of French researchers conducted this study.


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How the Study Worked

The study focused on a subgroup of HIV-positive women entering a larger study of cervical HPV infection and related conditions. Women who joined the anal HPV study never had anal cancer and agreed (1) to give an anal swab specimen for HPV testing, and (2) to undergo high-resolution anoscopy, a procedure that provides a magnified view of the anal canal. During high-resolution anoscopy, specimens of anal tissue can be snipped off and later tested to see if they are precancer or cancer.

Checking women's medical records with their permission, researchers collected medical details such as CD4 count, viral load, and current antiretroviral therapy. The research team used anal swab samples to test for high-risk HPV (HPV types more likely to cause cancer) and low-risk HPV (types less likely to cause cancer).

When women had high-resolution anoscopy, they completed a short questionnaire about sexual behavior and any anal disease. Women later had standard cervical testing for HPV and for cervical lesions. The investigators graded anal tissue and cells by systems used for cervical lesion staging, ranging from healthy, to various precancer stages, to cancer (Table 1).


Table 1. Anal Tissue and Cell Staging

Table 1. Anal Tissue and Cell Staging

AIN, anal intraepithelial neoplasia; ASC-US, atypical squamous cells of undetermined significance; SIL, squamous intraepithelial lesion.

* Atypical squamous cells, cannot exclude HSIL.


A main goal of the study was to see how many women had high-grade anal intraepithelial lesions (HG-AIN) or anal cancer; HG-AIN may develop into anal cancer. The researchers used accepted statistical methods to identify factors linked to HG-AIN or anal cancer. This type of analysis singles out individual risk factors regardless of whatever other risk factors a person has.


What the Study Found

The 171 women who had high-resolution anoscopy had a median age of 47.3 years and half of them were between 41 and 51 years old. Sixty-three women (37%) came from sub-Saharan Africa, and most women (61%) had 5 or more lifetime sex partners. Most women (89%) were taking antiretroviral therapy and had an undetectable viral load. Median CD4 count for the group stood at 655.

Sixty women (36%) had anal sex and 54 (33%) smoked. Anal sex may lead to anal HPV infection, and smoking raises the risk of anal precancer and cancer. More than half of the women (55%) had a record of low-grade squamous intraepithelial lesions (LSIL), which may develop into high-grade lesions and eventually result in cervical cancer. But cervical Pap tests at the time of this study were normal in most women (83.5%).

More than half of these women (58%) had high-risk HPV types (those that may cause cancer) in the anal canal. Eighty-one of 99 women (82%) with a high-risk HPV type had more than one high-risk HPV type. Almost 1 in 5 women (17%) had anal HPV-16, the HPV type most often linked to cancer.

Among 163 women with complete test results, 33 (20%) had low-grade anal lesions and 21 (13%) had high-grade anal lesions (HG-AIN) or cancer, including 1 woman with anal cancer, which was successfully treated. In total, one third of these women had a possibly dangerous anal lesion.

Statistical analysis that considers several risk factors simultaneously pinpointed two factors linked to higher chances of high-grade anal lesions or anal cancer regardless of whatever other risk factors a woman had (Figure 1). A record of cervical LSIL (low-grade cervical lesions) raised the odds 4 times, and anal HPV-16 raised the odds 16 times. Testing for high-risk HPV types or testing for HPV-16 plus anal cell analysis were the best ways to detect high-grade anal lesions or cancer in these women. Either approach would have detected 91% of cases.


Factors Linked to Anal Lesions in Women With HIV

Factors Linked to Anal Lesions in Women With HIV

Figure 1. In antiretroviral-treated women with well-controlled HIV infection, low-grade cervical lesions in the past were linked to 4 times higher odds of current high-grade anal lesions. HPV-16 detected in the anal canal was linked to 16-fold higher odds of high-grade anal lesions.


What the Results Mean for You

This study of HIV-positive women taking effective antiretroviral therapy and getting regular gynecologic exams found that one third of them had anal lesions (damaged tissue) that could get worse and might even develop into anal cancer. 1 More than 1 in 10 women had a more advanced type of lesion and 1 woman already had anal cancer.

HPV, a sexually transmitted virus, is well known as a cause of cervical cancer (an AIDS cancer) in women with HIV and of anal cancer in gay men with HIV. But this study is the first thorough analysis of HPV and anal cancer risk in a large group of HIV-positive women. The study found that women with a previous cervical cell abnormality were more likely to have a high-grade anal lesion or anal cancer. The researchers suggested that this link could mean HPV passed from the cervix or vagina to the anal canal of some women. In other words, women may not have to have anal sex to acquire anal HPV infection. Women with anal HPV-16, the HPV type most often linked to anal or cervical cancer, were more likely to have anal lesions than women without HPV-16.

Together, these findings strongly suggest that precancerous anal lesions are not rare in middle-aged women with antiretroviral-treated HIV infection and that HIV clinicians should check women for such lesions. The researchers stressed that collecting an anal sample for cell study is easy, fast, and painless and can be done in the HIV clinic without a specialized tool called an anoscope. The study showed that analyzing anal cells and testing women for high-risk HPV types, especially HPV-16, are a simple and reliable way to find HIV-positive women with anal lesions.

Because early detection and treatment of high-grade anal lesions may prevent anal cancer, the researchers believe HIV-positive women should be tested for such lesions and that those lesions should be treated or checked regularly. They suggested offering anal sample collection to HIV-positive women during their gynecologic exams.


References

  1. Heard I, Etienney I, Potard V, et al. High prevalence of anal human papillomavirus-associated cancer precursors in a contemporary cohort of asymptomatic HIV-infected women. Clin Infect Dis. 2015;60:1559-1568.
  2. Nielsen A, Munk C, Kjaer SK. Trends in incidence of anal cancer and high-grade anal intraepithelial neoplasia in Denmark, 1978-2008. Int J Cancer. 2012;130:1168-1173.
  3. Hessol NA, Holly EA, Efird JT, et al. Concomitant anal and cervical human papillomavirus infections and intraepithelial neoplasia in HIV-infected and uninfected women. AIDS. 2013;27:1743-1751.
  4. Peirson L, Fitzpatrick-Lewis D, Ciliska D, Warren R. Screening for cervical cancer: a systematic review and meta-analysis. Syst Rev. 2013;2:35.


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HPV Vaccine May Benefit HIV-Infected Women



This article was provided by The Center for AIDS Information & Advocacy. It is a part of the publication HIV Treatment ALERTS!. Visit CFA's website to find out more about their activities and publications.
 

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