Healthcare providers and researchers have serious uncertainties regarding current screening methods for anal cancer, according to a qualitative study from Canada published in Social Science & Medicine. The physicians navigated a tension between the need to avoid exposing their patients to additional uncertainties caused by screening and pre-cancer treatment, and the need to ensure that their patients did not develop anal cancer under their care. However, the high number of abnormal test results paradoxically reintroduced the capacity issues that the screening was meant to resolve.
Dr Mark Gaspar of the University of Toronto and colleagues interviewed 13 physicians and two clinical researchers with experience of anal Pap screening from Ottawa, Vancouver and Toronto. The interviews were conducted in 2016-2018 as part of a large research project called HPV-SAVE (HPV Screening and Vaccine Evaluation).
Anal cancer screening methods
Human papillomavirus (HPV) associated anal cancer is now one of the most significant non-AIDS cancers that affect gay and bisexual men living with HIV, at a rate greater than 100 times than in the general population. Anal cancer screening interventions include:
- Digital ano-rectal examination (DARE) – the clinician uses their gloved finger to feel for any lumps or swellings that may indicate pre-cancer.
- Anal Pap smears (cytology) – a small swab is passed just inside the anus to collect cells, which are suspended in fluid, stained and examined under a microscope. They are graded from least to more likely to flag pre-cancerous changes: negative (no abnormal cells), ASCUS (atypical squamous cells of undetermined significance), LSIL (low-grade squamous intraepithelial lesion) and HSIL (the same, but high-grade). The sample can also be tested for HPV.
- High-resolution anoscopy (HRA) – insertion of a thin, lighted, flexible tube with a magnifying device inside the anus. Abnormalities are biopsied and histologic results (from a microscopic examination) are graded similarly to cytologic results.
High-resolution anoscopy is regarded as the gold standard screening method, providing the most accurate results. However, it is more invasive, more costly and is only available at five specialist clinics in Canada.
Among other objectives, HPV-SAVE is evaluating anal cancer screening interventions. Gay and bisexual men living with HIV are offered Pap tests and those with abnormal results are invited for further screening with high-resolution anoscopy. Those with HSIL can join a randomised trial that compares ablative treatment (mechanical or chemical removal of lesions) to close surveillance (regular monitoring with high-resolution anoscopy and biopsies).
All 15 healthcare providers who participated in the study believed that anal cancer is a significant health concern for gay and bisexual men, particularly those who have HIV. Many of them had patients who had been diagnosed with or died of anal cancer, as this interviewee commented:
“But I’ve had two patients die from anal cancer. And you know, it impacts you when that happens. So I think it is really important.”
Generally speaking, they supported the implementation of screening programmes that included routine anal Pap testing, even though they questioned the tool’s utility. During interviews, they discussed a number of uncertainties and challenges.
Are anal Pap smears reliable?
Pap tests were used in the study as a triage tool for high-resolution anoscopy, but participants expressed scepticism over their reliability.
“There is a lukewarm feeling about the yield of this screening method.”
This reaction was not really surprising: while anal Pap testing has a high sensitivity for the detection of abnormalities, it has a low specificity when it comes to indicating their grades.
“I’m concerned with any result that’s not a negative. Even a negative. It’s a screening test and it’s not that good.”
Another issue was that some participants considered the correlation between Pap tests and high-resolution anoscopy results as poor. Several of them went as far as describing situations where they had had patients with high-grade Pap results that were not confirmed with the high-resolution anoscope; or patients with a negative cytology result who had later been diagnosed with anal cancer.
Challenges with cytology itself increased scepticism towards Pap results, for example, when compared to the precision of biopsies that allow to see if cells are invading different layers of tissue. One participant said:
“In cytology, you just get a bunch of cells, right? And so, I mean, arguably, how do you tell an invasive cell from a non-invasive cell, unless you can see it invading?”
Participants were also concerned with potential differences in the grading of the tissue samples, from one laboratory to another, sometimes collected from the same patient.
What do cytology results really mean?
Results of anal Pap tests were quite generally considered as ambiguous and therefore, not giving any clear idea about what to do with them. Some respondents went as far as thinking that only a high-grade result was useful to their follow-up practice.
“Because if you have a high-grade Pap, it’s coming from somewhere, right?”
Other results were too ambiguous, said another interviewee:
“Whereas everything else is like, well, maybe, maybe not. We just don’t know.”
"If physicians were confused, how could patients not be?"
Participants viewed the ASCUS (atypical squamous cells of undetermined significance) grade as the most ambiguous, with some even qualifying it as “bizarre” or “garbage”. ASCUS was one of the most common results, but did not “mean a hell of a lot”. Because “people don’t know what these results necessarily mean”, there was a potential for serious misinterpretation. For example, how would an inexperienced doctor react to a negative result, when the Pap’s less than 100% accuracy did not really allow for a conclusion such as “oh, everything is fine, there is nothing I need to worry about”?
Even for the specialists enrolled in the study, this ambiguity of results led to more uncertainty with regards to the interpretation of cytology results than among their counterparts working in gynaecology and cervical cancer screening. There are guidelines and resources to guide physicians’ follow-up after cervical screening, while with anal Pap testing, it was unclear what the next steps should be. Gay and bisexual men with HIV are a subpopulation within a minority population, which does not facilitate research into the issue or the development of guidelines and standardised clinical procedures.
Clearly, the confusion over how to respond to Pap results complicated the communication of such ambiguity to patients. If physicians were confused, how could patients not be?
How can test results be explained to patients?
After receiving Pap test results, patients asked numerous questions which called for specific answers. Of course, this depended on how these reacted to the news. Some could show a high level of acceptance:
“Okay, just tell me when I need to come in next.”
Or alarm:
“Do I have to tell my partner? What does this mean? How did I get this? I’ve already been living with a virus for however long and now I have to worry about something else again.”
Physicians needed an appropriate amount of time to provide patients with information on and around the Pap result:
“And it freaks people out. I spend a lot of time before I do the test, explaining that this does not diagnose cancer. I really, really go over it a lot and I just, I talk about atypical cells and you need to go for secondary screening, it’s a very long phone call.”
The word 'pre-cancer' was problematic. Participants expressed concern over how difficult it could be to convince their patients that it did not mean cancer, keeping in mind that, as robust as the information should be, it should not “drown” them. Physicians used several methods of communication, from trying to simplify the information, while being careful about getting them upset concerning pre-cancer, to explaining things “pragmatically” with a “proper kind of counselling” in order to “soften” the results, such as communicating clearly that the Pap “cannot determine whether or not you have cancer”.
Some doctors were selective with the information they provided. For example, one asked why bother telling patients that they have “atypical cells of uncertain significance” when they would not be followed up, and that the patients would not know what to do with this information?
The study investigators also report that several participants described how complex it was to present patients with information about their health that they could not address.
“You’ve now just told them there’s something I’m very concerned about. But let’s sit around for three years while they stew about this cancer they feel is growing inside them.”
Should pre-cancer be treated?
The question of treating pre-cancer or not was often raised. Evidence around treatment was “not really strong” but a participant had what he called a “natural instinct” to treat pre-cancer. Another one stated:
“In every instance in medicine where we find pre-cancers, they’re treated. So this would be a major exception. So cervical pre-cancers, vulvar, breast, colon, skin, there are all these pre-cancers that are treated. Nobody ever leaves pre-cancer to say “well, you know what? Let’s let it grow into cancer and then we’ll take it out”.
"Evidence around treatment was “not really strong” but a participant had what he called a “natural instinct” to treat pre-cancer."
Importantly, several of these physicians recognised their patients’ desires to have something potentially dangerous removed from their bodies.
There was concern about screening creating an endless cycle of testing and treatment:
“Once somebody is in that system, it’s very rare for them to leave… If they look close enough, they’re always going to find some cells and so then that means coming back every three months or every six months and using ablation. Unfortunately, it seems we don’t really seem to get anywhere.”
However, the available scientific evidence was too limited to allow for the determination of best practices regarding anal cancer screening, referral and treatment – including whether or not screening actually prevents mortality, or how frequently it should occur.
The epistemic-capacity paradox
Undoubtedly, the fifteen healthcare providers who were interviewed for this study were aware of the need for more evidence to support the development of clear guidelines. However, to reach this goal, they had to conduct a study based on a poorly accurate screening test – the Pap test – for referral to a more specific one – the high-resolution anoscopy.
But paradoxically, this practice reinstated the capacity issues it was meant to resolve, with existing dysplasia clinics being unable to follow-up all patients who had abnormal cells and had been referred to them. The very few specialist clinics and experienced pathologists in the country were completely overwhelmed, which did not encourage the respondents to make necessary referrals or even prevented them from recommending anal cancer screening to patients.
Gaspar and colleagues refer to this situation as the epistemic-capacity paradox, “a dynamic whereby seeking evidence to improve healthcare capacity simultaneously produces evidence that generates capacity challenges and introduces additional uncertainty”.
In their conclusion, Gaspar and colleagues try to answer the question of how to get out of the vicious circle they describe. One proposal would be to screen a much larger population, including all men who have sex with men and women, to gather more evidence. However, as this decision would still face the challenge of limited capacity in Canada, collaboration with other countries that are implementing anal cancer screening programmes would be welcome.
This would also require the mobilisation of advocacy skills and resources of the HIV sector and collaboration with other medical fields, “to establish procedures or share strategies that can help develop best practices more effectively in the context of addressing rarer conditions”.
“Finally”, they state, “evidence alone does not just drive implementation: politics does as well”.
Gaspar M et al. Diagnosing uncertainty: The challenges of implementing medical screening programs for minority sub-populations in Canada. Social Science & Medicine, 244: 112643, 2020.