HIV JournalView

Low HIV Viral Load May Reduce Anal Cancer Risk; Spontaneous Regression Is Common

June 21, 2013

Two recent studies help shed new light on the risks of anal cancer among men living with HIV -- a growing concern among our patients, particularly for men who have sex with men.

Protective Benefits of Antiretroviral Therapy

The first study, which was published ahead of print in the online edition of JAIDS, found that for men living with HIV, having and sustaining an undetectable viral load reduced the risk of developing anal cancer.

Researchers at the U.S. Department of Veterans Affairs analyzed patient data from 1985 to 2009. In total, they collected data on 45,231 HIV-infected men spanning 307,495 person-years. They compared the differences between men who had received HIV treatment and those who were treatment-naive, looking in particular at the incidence rate of squamous cell cancer of the anus (SCCA). Overall, they found 377 cases of anal cancer.

Key findings include:

  • In terms of SCCA incidence rate, there was no statistically significant difference between those who had received treatment and those who had not (146.8 vs. 134.3 cases per 100,000 person-years).
  • Viral load was a key risk factor. The risk of developing anal cancer was reduced by about 50%, both for those who maintained an undetectable viral load 61%-80% of the time (P = .004) and those who did so 81%-100% of the time (P = .00004), when compared to men who had an undetectable viral for only 20% of the time.
  • Having a higher CD4+ cell count (both current and nadir) reduced the risk of developing anal cancer.

"This is the first large cohort study to demonstrate that maintaining undetectable viral load independently decreases the incidence of SCCA above and beyond other known SCCA risk factors," the researchers wrote, according to


These results are limited by the study's retrospective design. The study also did not focus on men who have sex with men, the group with the highest rates of anal cancer among people living with HIV. But it nonetheless provides still another reason for patients to start and adhere to antiretroviral treatment.

"I think that other studies and ours have shown a very strong effect on anal cancer risk from low nadir CD4 counts," lead study author Elizabeth Chiao, M.D., M.P.H., told "In our study, we used a CD4 count above 350 as a cutoff. We can't really say from our analysis that treatment regardless of CD4 count decreases risk, but there certainly is a strong implication that higher is better."

Chiao also pointed out four other ways to help prevent anal cancer for men living with HIV: quitting smoking; getting routine anal cancer screenings; decreasing exposure to high-risk HPV (human papillomavirus); and getting the HPV vaccine (Gardasil) if under the age of 26.

Joel Palefsky, M.D., one of the leading experts in HIV, HPV and anal cancer, found the results encouraging, but expressed some caution. He compared the study's SCCA incidence rate of about 147 cases per 100,000 person-years to the current incidence rate of cervical cancer in women, which is approximately 8 cases per 100,000 person-years.

"Even with the people who have the sustained reduction in viral load, the rates of anal cancer are still way too high. My concern here is that people don't say, 'I've had an undetectable viral load for a long time. I don't need to worry about it,'" he told

Lesion Regression Is Extremely Common; Beware of Aggressive Treatment

The second study, which was published ahead of print in the online edition of AIDS, found that high-grade, pre-cancerous lesions were more likely to spontaneously regress than progress to cancer.

Some quick context: Anal cancer is caused by high-risk strains of HPV. It is preceded by high-grade pre-cancerous anal lesions, also known as high-grade anal squamous intraepithelial lesions (ASILs). These high-grade ASILs are classified into grade-2 anal intraepithelial neoplasia (AIN2) or grade-3 anal intraepithelial neoplasia (AIN3), both of which are considered high-grade anal intraepithelial neoplasia (HGAIN).

Researchers from St. Vincent's Hospital in Sydney, Australia, analyzed data on 574 men who had received an anal Pap smear or high-resolution anoscopy (HRA) from 2004 to 2011. About three quarters were living with HIV; they had a median CD4+ cell count of 500 and about 84% had an undetectable viral load.

Key findings are as follows:

  • In total, only 1% of those with high-grade ASILs progressed to anal cancer. By comparison, there was a 24% regression rate.
  • Among the 152 patients who were eligible for disease progression analysis, 19 individuals (or 12.5%) developed HGAIN.
  • The incidence rate of progression to HGAIN was 7.4 per 100 person-years, but there was no statistically significant difference between HIV-infected and uninfected men.
  • There was a statistically significant difference in the incidence rate of progression to AIN3 between HIV-infected and uninfected men (13.1 vs. 4.5 per 100 person-years).
  • Among the HIV-infected men, nadir CD4+ cell count below 200 was considered a risk factor for progression to AIN3.
  • Out of 101 patients that had developed HGAIN, 24% experienced spontaneous regression of the disease. Of this 24%, biopsy revealed that 71% regressed to grade-1 anal intraepithelial neoplasia (AIN1), while the other 29% became completely cleared of the disease.
  • Out of 55 patients that had developed AIN3, 47% experienced spontaneous regression of the disease, with similar rates among both HIV-infected and uninfected men.
  • In total, four patients developed anal cancer, but only two had HGAIN prior to their diagnosis.

"Our data provide reassurance that high-grade ASILs diagnosed at any one point are much more likely to spontaneously regress than progress to cancer. Not all patients with high-grade ASILs warrant treatment," wrote the study authors, according to

"Our data support current guidelines that recommend any abnormality on anal cytology warrants further investigation with HRA, as two of four incident anal cancers had only low grade cytology a short time before the diagnosis of cancer," the authors added.

While the high rates of spontaneous regression of pre-cancerous anal lesions are promising, they don't tell the full story. The researchers hope to conduct future studies to identify risk factors and biomarkers that may predict the highest risk of progression to anal cancer.

However, Palefsky again expressed caution over the results. "I'm a little concerned people will misconstrue these findings, because they only followed people for one year and cancer takes many years to progress. Even in this one-year period, two people out of 101 [who had HGAIN] progressed to cancer. That's enormous," he told

"The other thing that's concerning is that you very rarely see a study where they show that people lost their HPV. If the HPV is still there, then it's just waiting to turn into a high-grade lesion," Palefsky added.

In terms of anal cancer prevention methods, Palefsky echoed Chiao's recommendation of routine anal cancer screenings, if available, particularly for all HIV-infected men and women under 30. If anal cytology and HRA are not available, "At a minimum, do an annual digital anal rectal exam, where the care provider would be putting their finger in and feeling for hard lumps that might be diagnostic of cancer. So, at least, if there's a cancer there already, it'll be picked up as early as possible."

Palefsky also recommended close communication with the patient about potential lesions. "Talk to the patient," he urged. "There are certain signs we worry about -- when people tell us, for instance, that they have a rapidly growing lump down there, particularly if that lump is associated with pain, because pain can sometimes be a sign of cancer. If they get a good history from their patient and know what's going on, that should also potentially alert them to the possibilities that this could be cancer."

Overall, both studies give clinicians more insight into how to handle concerns over anal cancer, including how to help prevent and identify risk factors. This research provides some welcome news while we await future studies to help clarify what further steps to take.

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Warren Tong is the research editor for and

Follow Warren on Twitter: @WarrenAtTheBody.

Copyright © 2013 Remedy Health Media, LLC. All rights reserved.

This article was provided by TheBodyPRO. It is a part of the publication HIV JournalView.

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