Well this is a study to answer a very basic question that people have who are taking care of individuals at increased risk of anal cancer you know cancer is a very bad disease it causes a lot of mortality when cause when diagnosed late stage but even people diagnosed at early stage have a higher survival rate but the morbidity rate from the treatment is very high so whether somebody's diagnosed early or late it's a disease that is much better prevented than diagnosed after it has occurred HPV is the cause of anal cancer just like it is cervical cancer human papilloma virus and we also know that anal cancer is preceded by high-grade pre-cancerous changes very similar to what we see in the cervix so we think of cervical cancer as being very similar to anal cancer and since we know that we can prevent cervical cancer not only through HPV vaccination as primary prevention but through secondary prevention in the form of pap smear screening identification of cervical high grade lesions through colposcopy and removal of those high grade lesions to prevent cancer that works very well we thought perhaps we could do the same thing for anal cancer again primary prevention for anal cancer is HPV vaccination to prevent initial HPV infection but we need secondary prevention as well because many people at risk renal cancer may be too old to have been vaccinated against HPV so secondary prevention is the only opportunity to prevent cancer in those individuals and the question is if we look for and diagnosed anal high-grade squamous intra-epithelial lesions the cancer precursor HSIL for short can we reduce the risk of anal cancer there are certain populations where anal cancer is unacceptably high in the general population the incidence is pretty low more common in women than men and increasing by about two to three percent per year since the 1970s but certain risk groups are known to be at particularly high risk of anal cancer and the highest risk group of all are people living with HIV and of people living with HIV the highest risk group are men who have sex with men but women with HIV and males who are not MSM also are at increased risk of HIV other risk groups include women who've had an HPV-related cancer or pre-cancer elsewhere in the inner genital tract such as the cervix or the vulva and also people who are immunosuppressed for reasons other than HIV such as solid organ transplant so we know who the risk groups are people with HIV definitely the highest risk of all so we thought if we're going to try a method to prevent anal cancer through secondary prevention let's start with this group and so the study that we did was called the ANCHOR study called ANCHOR because it's the ship's ANCHOR and it stands for anal an cancers the CH cell is the age outcomes research study and the idea was a simple one which was to do a randomized controlled trial asking whether amongst people who have the cancer precursor H-ZOL if we treat them can we reduce the incidence of anal cancer and to do a study like that the control group was a group in which we did what was called active monitoring namely very close follow-up of these ancient lesions without treatment so to do a study like this we recruited for screening 10,723 men and women living with HIV over the age of 35 and then looked for HCL using high resolution endoscopy if they had h cell on biopsy and met the other study inclusion and exclusion criteria then they were offered randomization and if they agreed they were randomized one to one to treatment versus active monitoring and then we followed up both groups over time and counted up the number of cases of anal cancer in both arms for statistical reasons target was 31 cases of anal cancer at which point our protocol called for us to have the data reviewed by the data and safety monitoring board the DSMB we actually reached 32 cases and notified the DSMB and ended up doing an analysis based on 30 because two cases were subsequently determined to have been ineligible because they were diagnosed with anal cancer prior to randomization so when the DSMB analyzed the 30 cases nine ended up being in the treatment arm and 21 in the monitoring arm which was a statistically significant difference and translates into a 57 reduction in anal cancer in the treatment arm compared with monitoring so at that point the primary study question was it addressed and the DSMB recommended stopping the study and offering treatment to everybody who had been in the monitoring arm who wish to have treatment at that point so basically in this study in which we randomized 4446 people we found for the first time in a randomized controlled trial that looking for anal h cell and treating it was effective in reducing the incidence of anal cancer so we feel that this is the first evidence that proves that a an approach to preventing anal cancer can be done similar to what we do in the cervix and are working with various regulatory entities to use these data towards development of standard care guidelines for people living with HIV.
Common Questions From Your Colleagues?
Well, the first question that people ask very commonly is okay what should I do now for my patients with HIV and here I need to mention what the ANCHOR study did and what the ANCHOR study did not do ANCHOR study was his treatment strategy study where we were not actually comparing different forms of treatment for the NOH cell but rather the decision to treat versus not treat i.e. to follow carefully the data as I mentioned showed that treating actually works but the study was not designed to say this treatment should be used versus that treatment as it happens almost all of the people in the study were treated with a modality called uh ablation it was office based ablation most often electrocautery in the form of hyfrecation and we feel that even though ANCHOR was not designed to test one treatment over the other uh so many of the people in the study were treated with hyfrecation that the benefits that we saw in ANCHOR could be attributed to that so one question I get asked is how do I treat patients and the answer is hyfrecation is a very reasonable starting point or some other form of office based ablation using a Bovee using laser if you have that or using infrared coagulation but another big question is how do I screen and decide who gets high resolution endoscopy to find these lesions in the first place and to guide the treatment the method used is high resolution endoscopy which is the equivalent of cervical colposcopy the problem we have right now is that the skills needed to perform HRA take a long time to develop if you want to become a really good high resolution endoscopy takes a very extensive period of training we have a very limited supply of people who are trained in high resolution endoscopy right now and so part of the problem is we cannot send everybody who's HIV over the age of 35 for HRA because we simply don't have the person power to do that so we need to have screening algorithms to decide who gets HRA and who doesn't this is what we do in the cervix we don't send all women for cervical colposcopy we do a screening test first either in the form of cervical cytology or pap smears with or without HPV testing we need something similar in the anus and ANCHOR study was not designed to test different screening algorithms because we did HRA and everybody to find the biopsy proven h sill that was one of the entrance criteria so one of the key questions is going to be what to do to decide who amongst your patients should go for HRA we are actually working with different agencies right now to come up with some guidelines to recommend different screening approaches until we have more definitive data ANCHOR itself will actually provide us with a lot of data that will help in this but those data are still being analyzed and for now we recommend that you go to the CDC guidelines for the care of opportunistic infections and people with HIV for further information there we hope over the next few months will be information on how to use anal cytology how to do anal HPV testing uh when to send your patients for HRA when you can just follow them with a repeat test later if the initial results are negative so the screening approach is very important one other thing that I do want to emphasize though is that there is a test that we recommend that everybody do regardless of whether or not you can do anal cytology or HPV testing or regardless of whether or not you can do or send somebody for HRA and that is a digital anal rectal exam or a dare I want to emphasize here that we have two different kinds of screening tests here the dare which uses your finger is meant to detect a prevalent anal cancer when you put your finger in you feel something hard we often feel small soft mobile lumps when we put our finger in but if you feel something hard and immobile that is more suspicious for a cancer and so to do the so-called anal cancer screening test we recommend that everybody living with HIV get a digital anal rectal exam probably once a year and if you are in living or practicing in an area where you can send your patients for HRA based on any additional screening tests that you do then we recommend that where those additional screening tests are the screening tests for HCL so the cytology the HPV testing done through anal swabs are the tests that you would do to decide which of your patients goes for HRA so in other words all patients should get a digital anorectal exam if you're in an area where you can refer your patients or if you're performing charity yourself if an abnormal pap test comes back or a positive HPV test then we recommending we recommend doing those tests based on the guidelines that we hope will be coming up shortly by CDC and other entities.
Will This Effect Clinicians Today?
We do think the data will affect clinicians today because now that we know that we can prevent anal cancer it underscores the importance of taking measures number one to make sure that primary prevention is done through HPV vaccination for people who are of appropriate vaccination age that includes men and women but the data speak even more directly to the need to start secondary prevention measures for people who are too old or don't have access to the HPV vaccines so what that really means is start doing your digital rectal exams because those rates of cancer are increasing and two you should consider figuring out in your practice environment whether there is somebody who you can refer your patients to should those cytology or HPV tests come back abnormal if you don't then we recommend sticking with the dare until you do but if you do right now it's reasonable to start screening your patients based on the guidelines that we hope will be appearing soon so we don't think it's going to be very long uh until those come out they will be modified as additional data come in but this is a new standard of care practice that we expect will be adopted uh in the next few months we hope and this is an important piece of preventive medicine to add for the care of patients with HIV the other question that we get asked a lot actually is what do the data mean for my high-risk patients who don't have HIV and this is a point where we're going to have more discussions with different stakeholders question being can we take the data that we learned from people with HIV and extrapolate them to people who don't have HIV my own personal feeling is that yes we can and should because people living with HIV are some of the toughest people of all to treat and my feeling is that if we can be successful in reducing anal cancer in this very challenging group we should be at least if not more successful in some of the other groups that I mentioned earlier the women with HPV related disease elsewhere transplant recipients etc. so that in all likelihood secondary prevention should be possible in those groups as well where it gets a little dicey is whether uh various agencies who that make recommendations for standard care are willing to accept data from a population that was all HIV positive to extend those to these non-HIV positive groups and that's a discussion that we're going to have uh if for no other reason because replicating the ANCHOR study in those other groups is probably going to be extremely difficult if not totally impossible and so I think these are the data that we are going to have to work with and we're going to have to make a decision about whether we're willing to accept them for those other groups.
What Are The Next Steps?
Well there's a lot of next steps coming the one of the next steps is to use some of the data that we and others have to try and refine the screening algorithms to help people determine which tests they should use psychology or HPV or both and at what intervals another important step in research is actually improving the treatments for anal h cell although we were able to reduce the risk of anal cancer quite substantially with these office-based ablation methods there were still some people in the treatment arm who progressed to cancer despite efforts to prevent it and so we definitely need more research on even better treatments for anal H cell and one of the entities that is involved in this is the aids malignancy consortium of the national cancer institute and so we are actively looking at other approaches to treating NHL cell therapeutic vaccinations new topical therapies to try and make it easier and more effective to treat these lesions over time that's another very important research component another one that's important is to analyze cost-effectiveness data it'll be very important to look at what these data look like in different populations amongst people with HIV starting at what age are is the cost effectiveness acceptable Another group at high risk of anal cancer and who should also be considered for anal cancer screening programs are HIV-negative men who have sex with men. What does the cost-effectiveness look like in the other non-HIV populations these are important research questions and then another a very important endeavor that needs to occur not so much a research issue but an implementation issue is to ramp up the training of people who know how to do HRA and who know how to treat lesions because as I mentioned earlier one of the significant limitations that we have right now is a shortage of people who know how to do this we really need to increase the number of people who know how to do this and we need to also learn how to train people faster and more efficiently
Well I encourage everybody to read the paper that describes the primary findings of the ANCHOR study which was published in the June 16th issue of the New England Journal I think it's really important particularly for people taking care of people with HIV right now to be aware of this development because cancer prevention is becoming increasingly important as the population with HIV ages anal cancer is going to become more common in older people and so this is a relatively straightforward procedure that can be done to reduce a lot of morbidity and potentially mortality your patients also are going to be asking about it so i think it's good to understand the uh this new development and ideally make a plan for reaching out to others in the in your practice environment to be able to take care of patients who might be uh at risk for anal h cell by virtue of the screening tests that that we've been uh discussing also I strongly recommend that people taking care of people with HIV reach out to their surgical colleagues because when you do your digital rectal exam it's important to have somebody who knows what to do when you feel that mass that feels suspicious for cancer they will need to have an endoscopy probably under anesthesia to make sure that it isn't cancer to do necessary biopsies etc.. so it's a great opportunity to reach out to your surgical colleagues also a great opportunity to reach out to your pathology colleagues some of you who may be starting to do anal psychology for the first time will be sending those specimens to psychologists or pathologists who may not have seen these before so I strongly recommend that you develop a strong working relationship with the pathology and cytology community that they know that these are coming that they're accustomed to seeing them and that you're working closely together to get the best diagnosis on your patients so you know how to best refer them.
Joel Palefsky, MD, Professor of Medicine at University of California San Francisco. In this interview, he speaks about the Treatment of Anal High-Grade Squamous Intraepithelial Lesions to Prevent Anal Cancer.
The trial's randomized phase compared topical or ablative treatment with active monitoring in preventing anal cancer in people with HIV and high-grade squamous intraepithelial lesions (HSIL). Anal HSIL is anal canal tissue that has been damaged by human papillomavirus (HPV) infection and is at risk of developing into anal cancer.
Based on the data and statistical analysis given to them on 07SEP2021, the ANCHOR Data Safety Monitoring Board (DSMB) assessed that the primary study endpoint had been met.
During the post-randomization phase of this experiment, all recruited patients are offered HSIL treatment and/or follow-up at their discretion.