Long Lag Time in Anal Pap Follow-up for People With HIV

Heather Boerner

November 16, 2020

It took an average of 380 days for people who had received an abnormal anal Pap test result after having been diagnosed with HIV to undergo high-resolution anoscopy (HRA), which is recommended as follow-up.

That delay "revealed missed opportunities for a better experience on the patient, clinic, and provider level," Jessica Wells, PhD, research assistant professor at the Nell Hodgson Woodruff School of Nursing at Emory University, Atlanta, Georgia, told Medscape Medical News. After all, she said, "a lot can happen in that 1 year," including early development of human papillomavirus (HPV)–associated anal cancer.

Although it's too soon to say how significant that delay is with respect to the natural history of anal cancer, Wells said the data are a potential signal of disparities.

"The findings from my study may foreshadow potential disparities if we don't have the necessary resources in place to promote follow-up care after an abnormal Pap test, similar to the disparities that we see in cervical cancer," she said during the virtual Association of Nurses in AIDS Care (ANAC) 2020 Annual Meeting.

Single-Center Study

In the United States, people living with HIV are 19 times more likely to develop anal cancer than the general population, according to a 2018 article in the Journal of Clinical Oncology. Another single-center study from Yale University found that in minority communities, anal cancer rates were 75% higher than in White communities. Anal cancer rates were 72% higher in communities with greater poverty. As a result, many clinics are beginning to adminster Pap tests to determine early signs of HPV infection and associated changes.

In Wells' study, which was conducted from 2012 to 2015, 150 adults with HIV who were aged 21 and older were recruited from Grady Ponce De Leon Center in Atlanta. According to a 2018 study from that center, a large minority of participants had late-stage HIV and suppressed immune systems.

All participants had been referred for HRA after a recent abnormal anal Pap test. Participants filled out questionnaires on sociodemographics, internalized HIV-related stigma, depression, risk behaviors, social support, and knowledge about HPV and anal cancer.

Participants were disproportionately older (mean age, 50.9 years), cisgender (86.7%), Black (78%), and gay, lesbian, or bisexual (84.3%). Slightly more than 1 in 10 participants (11.3%) were transgender women.

Although for 6% of participants, Pap test results indicated high-grade squamous intraepithelial lesions (HSIL), an additional 8% had atypical Pap findings that couldn't exclude HSIL — the kinds of results that are one step away from a cancer diagnosis. More than 80% of participants had low-grade or inconclusive results. Nearly half (44%) of participants' Pap tests revealed low-grade squamous cell intraepithelial cell lesions (LSIL); 42% indicated atypical squamous cells of undetermined significance.

When Wells looked at how long participants had waited to undergo HRA, she found something that surprised her: although some participants underwent follow-up assessment in 17 days, for many, it took much longer. The longest wait was 2350 days ― more than 6 years.

"There were quite a few patients who had follow-up beyond 1000+ days," Wells told Medscape Medical News via email. "I didn't think the delays were that long — at most, I would say that patients will get scheduled and come back within a few weeks or months."

What's more, she discovered through the HPV knowledge questionnaire that many participants did not understand why they were having a follow-up appointment. Anecdotally, some confused HPV with HIV.

"There's education to be done to inform this target population that those living with HIV are more prone or at increased risk of this virus causing cancer later," she said. "There are a lot of campaigns around women living with HIV, that they need to do cervical cancer screening. I think we need to really expand this campaign to include that HPV can also cause anal cancer."

Wells had planned to primarily investigate the impact of psychosocial factors on wait time to follow-up, but none of those factors were associated with longer wait times.

Systems-Level Factors

That led Ann Gakumo, PhD, chair of nursing at the College of Nursing and Health Sciences of the University of Massachusetts Boston, in Boston, Massachusetts, to ask what other factors could account for the delay.

There were several, Wells said. Precarious housing, for example, could have influenced this lag in follow-up. About 1 in 4 participants were in transient housing, and one participant reported having been incarcerated. She gathered street addresses and plans to analyze that data to see whether the cases occurred in clusters in specific neighborhoods, as the Yale data indicated.

In addition, the anoscopy clinic was only available to receive patients one day a week and was staffed with only one clinician who was trained to perform HRA. Wait times could stretch for hours. Sometimes, participants had to leave the clinic to attend to other business, and their appointments needed to be rescheduled, Wells said.

In addition to the sometimes poor understanding of the importance of the follow-up test, Wells said, "We start to see a layering of these barriers.

"That's where we start seeing breakdowns," she said. "So I'm hoping in a larger study I can address some of these barriers on a multilevel approach."

This resonated with Gakumo.

"Oftentimes, we put so much of the responsibility for this on the part of the client and not enough on the part of the provider or on the systems level," she said.

Guiding Guidelines

Guidelines on follow-up for abnormal anal Pap test results are scarce, mostly because, unlike cervical cancer, the natural history of HPV-related anal cancers hasn't been established. The HIV Medical Association does recommend anal Pap tests, but only in cases in which "access to appropriate referral for follow-up, including high-resolution anoscopy, is available."

In an interview with Medscape Medical News, Cecile Lahiri, MD, assistant professor of infectious disease at Emory University, said that at Ponce De Leon Center, they recommend an anal Pap for women with HIV who have a history of cervical dysplasia.

There is a reliable association between high-grade abnormal Pap tests and cervical cancer, although low-grade changes can resolve on their own. In the case of anal cancer, especially in patients with HIV, low-grade cell changes are predictive; moreover, for such patients, anal cancer is more likely to recur and is harder to treat, Lahiri said.

"The cervical environment and the anal environment are very different," said Lahiri, who works at the Grady Ponce De Leon Center but was not involved in Wells' study. Lahiri is also a co-investigator of the multisite, randomized, controlled Anal Cancer HSIL Outcomes Research (ANCHOR) study, which seeks to establish whether early treatment of high-grade anal Pap changes is better than a watch-and-wait approach.

Lahiri said that when the results of that trial become available, they are more likely to know how important early anoscopy and treatment are. The findings should inform guidelines and insurance coverage of anal Pap tests and anoscopy.

In the meantime, she said, she suspected that, with the ANCHOR trial in 2015, many sites' capacity for anoscopy may have increased, and the wait times may have gone down.

"One of the most important pieces of the study is actually the time period in which it was conducted," said Lahiri, who in 2015 became the clinic's second physician trained in anoscopy. Currently, more than 200 people at the Ponce De Leon Center are enrolled in the ANCHOR trial. In addition, the general capacity for performing anoscopies has gone up nationwide as a result of the trial, which required that more providers learn how to properly perform an HRA. Many clinicians are not routinely trained in performing HRA, including gastroenterologists and surgeons, Lahiri said.

"It would be interesting to look at the differences, with the start of ANCHOR being the time point for before and after," she said.

Association of Nurses in AIDS Care (ANAC) 2020 Annual Meeting: Abstract LB-4. Presented November 12, 2020.

Heather Boerner is a science and medical reporter based in Pittsburgh, Pennsylvania. Her book, Positively Negative: Love, Sex, and Science's Surprising Victory Over HIV, came out in 2014.

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