By Dr. Ed Weiss (biography and disclosures) Disclosures: Clinical trials with the University Health Network. Mitigating Potential Bias: Recommendations are consistent with current practice patterns.
What I have noticed
Over the last forty years, epidemiologists have noted a striking increase in the incidence of squamous cell carcinoma of the anus. In the United Kingdom, for example, incidence rates have increased by over 60% between 1993 and 2015, while 5-year mortality rates have hovered around 65%.(1) Close to 90% of anal cancers are associated with high-risk HPV subtypes, such HPV-16,(2)which cause oncogenic transformation of the anal canal and perianal skin in a manner that parallels the development of cervical cancer. People living with HIV and other immunosuppressed states have traditionally been considered at the highest risk for the development of anal cancer; those with HIV who are also men who have sex with other men (MSM) have a relative risk that is 50-100 times that of the general population.
In Canada, the incidence of anal cancer in the general population is around 1.7 per 100,000 person/years; the increased risk in HIV positive MSM would thus be even higher than the incidence of colorectal cancer in men, which is about 60 per 100,000 person/years.(3)
As is the case in the cervix, anal cancer begins with a long and asymptomatic phase of non-invasive high-grade dysplasia, with an annual risk of transformation to cancer that ranges between 1-10%.(4) During my medical training, I became aware of the increased risk of anal cancer among MSM, and I heard vaguely about the use of anal pap swabs to screen for precancerous anal lesions, but I was never able to clarify how to use anal cytology as a screening tool, nor was it ever clear what I was supposed to do with abnormal results! In order to learn more about the role that primary care clinicians can play in recognition and prevention of anal cancer, I embarked on a formal training program in High Resolution Anoscopy (HRA), which is the anal equivalent of colposcopy for cervical lesions. Through the Immunodeficiency Clinic at Toronto General Hospital, I shadowed experienced clinicians and eventually joined the group as a part-time anoscopist in 2015.
Data that answers these questions
One of the more surprising things that I learned through my training was that there is no strong RCT evidence to support screening for anal cancer. Specifically, there is a lack of evidence that treating pre- cancerous dysplasia prevents progression to invasive anal cancers, although there is a general consensus that detecting and treating anal cancers early in their development leads to better long-term outcomes. Although trials (such as ANCHOR) are currently being conducted to clarify whether screening has long term benefit, it will be some years before we know the results, and even then, the findings will only address screening in the HIV-positive population.
In the interim, I feel it is imperative that we try to do better for our patients. We know that the diagnosis of anal cancer in Canada is often delayed: ano-rectal symptoms such as pain and bleeding are often attributed to hemorrhoidal disease and clinicians are often hesitant to perform a digital ano-rectal examination (DARE).(5) In my experience so far, I have seen that even when patients are referred for a colonoscopy, subtle anal canal lesions can often be missed due to the inability to examine the anal mucosa in fine detail. So, what can we do?
What I recommend (practice tip)
Be aware of people at risk
As mentioned, HIV-positive MSM are at the highest risk for anal cancer, but there are a number of other populations who are also at elevated risk, including: HIV-negative MSM, women with HIV, men and women who have had a previous genital HPV-related lesion (such as high grade dysplasia or cancer of the cervix, vulva, or penis), organ transplant recipients, and others with significant immunosuppression. Cigarette smoking and a history of multiple sexual partners are also risk factors and should be taken into account when obtaining a history.
Anal cytology needs to be part of an integrated pathway of care
Because Pap tests are limited in their sensitivity and specificity, the success of cervical cancer screening depends on repeat examinations and timely access to colposcopy, where the presence of high-grade dysplasia can be definitively confirmed and treated if necessary. Unfortunately, when it comes to the anus, there is very limited access in Canada to clinicians who perform HRA, which is the gold standard for diagnosing and treating anal dysplasia; currently there are only a handful of us, located mostly in major urban centres such as Toronto, Vancouver, and Montreal. Internal dysplasia cannot be visualized with the naked eye, and thus colorectal surgeons are not usually in a position to offer local ablative treatment. Dysplasia in the absence of invasive cancer is also not amenable to radiation therapy. Therefore, doing anal Pap smears is not advised in most situations, unless there is an established referral pathway for access to HRA.
Dare to DARE
What I now counsel colleagues is that the importance of a DARE cannot be overstated. While there are no official guidelines regarding this particular intervention, it is worthwhile for clinicians to consider a screening examination every 1-2 years for people who are at high risk for anal cancer. Additionally, any new symptomatic complaint of anal pain, discomfort, or bleeding should prompt a DARE in patients with risk factors for anal cancer, and in those without obvious risk factors who are over the age of 50. It is especially important to perform a DARE if there is no thrombosed hemorrhoid or fissure visible on examination to explain the presence of pain. I inspect the perianal skin for any nodules, erosions, or fissures. Doing a thorough, quadrant-by-quadrant sweep of the anal canal (with plenty of lubricant, or with lidocaine jelly), I palpate every aspect of the mucosa and feel for induration, nodules, or tenderness. Intra-anal warts are surprisingly common, especially among people who have receptive anal sex, and can be identified by their verrucous texture; they should not cause any pain or tenderness on examination, and the presence of painful warty nodules should raise red flags for an underlying cancer. Exquisite generalized tenderness may be a sign of an anorectal infection, such as lymphogranuloma venereum, and swabs for chlamydia and gonorrhea should be obtained.5 If there are any concerning features on DARE, a general surgeon with expertise in oncology should be consulted for consideration of an examination under anesthesia and biopsy. Confirmation of invasive cancer should prompt cross-sectional imaging for staging purposes, and referral to a radiation oncologist, if the patient’s goals of care are consistent with intensive treatment.
Encourage HPV vaccination
Prevention of anal cancer is just one more reason to encourage young people to get vaccinated against HPV prior to the initiation of sexual activity. We hope that widespread vaccination will ultimately change the course of history and make anal cancer a thing of the past!
Further reading and resources for clinicians and patients
- https://analcancerinfo.ucsf.edu
- https://www.bmc.org/sites/default/files/Anal-Cancer-Brochure_AMC.pdf
- https://www.youtube.com/watch?v=O1-sXsS7uEA
- http://www.providencehealthcare.org/infectious-diseases
BC Cancer Primary Care Program (Family Practice Oncology Network-FPON) Note:
Billing: Of note, there is an “In-office Anoscopy” fee (Y10710) here in BC that may be billed in addition to an office visit if the FP does anoscopy (which is far more likely to pick up the anal cancer than a digital rectal exam) as part of an assessment.
There is currently no BC Primary Care Anal Cancer Guideline. There is a guideline in Alberta dated 2013 (https://www.albertahealthservices.ca/assets/info/hp/cancer/if-hp-cancer-guide-gi001-anal-canal.pdf) that states “Because prognosis depends upon the stage of disease, an anatomic assessment with digital rectal examination, anoscopy or sigmoidoscopy (with biopsy), and a CT scan of the abdomen and pelvis (and/or MR or transrectal ultrasound) plus chest x-ray are recommended.”
The JNCCN 2018 article http://www.jnccn.org/content/16/7/852.full states “The panel recommends a thorough examination/evaluation, including a careful digital rectal examination (DRE), an anoscopic examination, and palpation of the inguinal lymph nodes, with fine-needle aspiration and/or excisional biopsy of nodes found to be enlarged by either clinical or radiologic examination.”
The ESMO-ESSO-ESTRO Clinical Practice Guidelines (https://www.esmo.org/Guidelines/Gastrointestinal-Cancers/Anal-Cancer) for diagnosis, treatment and follow-up in its screening and prevention section states: “The existence of an identified viral aetiological agent and the ability to detect pre-neoplastic lesions may allow the development of screening and prevention programmes. Vaccination of girls against oncogenic HPV is now being recommended for the prevention of cervical cancer, and a recent report indicated that up to 80% of anal cancers could also be avoided with prophylactic quadrivalent HPV vaccine (against HPV types 6, 11, 16 and 18). But currently vaccination has no role when SCCA is actually present [2]. Screening programmes using anal cytology and high-resolution anoscopy have been proposed for high-risk populations (MSM and HIV– women with a history of anal intercourse or other HPV-related anogenital malignancies) based on the achievements obtained in cervical cytology screening. However, no randomised control study has yet demonstrated the advantage of screening in these high-risk populations.)”
References
- Cancer Research UK. Anal cancer incidence statistics. Updated January 24, 2018. Accessed October 13, 2018. (View)
- de Martel C, Plummer M, Vignat J, Franceschi S. Worldwide burden of cancer attributable to HPV by site, country and HPV type. Int J Cancer. 2017;141(4):664-670. DOI: 10.1003/ijc.30716. (View)
- Medford RJ, Salit IS. Anal cancer and intraepithelial neoplasia: epidemiology, screening and prevention of a sexually transmitted disease. CMAJ. 2015; 187(2):111–115. DOI: 10.1503/cmaj.140476. (View)
- Berry-Lawhorn JM, Palefsky JM. Progression of anal high-grade squamous intraepithelial lesions to anal squamous cell carcinoma and clinical management of anal superficially invasive squamous cell carcinoma. Semin Colon Rectal Surg. 2017;28(2):91–96. DOI: 10.1053/j.scrs.2017.04.007. (Request with CPSBC or view with UBC)
- Chiu S, Joseph K, Ghosh S, Cornand RM, Schiller D. Reasons for delays in diagnosis of anal cancer and the effect on patient satisfaction. Can Fam Physician. 2015;61(11):e509-516. (View)
- Weiss ES, Sano M. Proctocolitis caused by lymphogranuloma venereum. CMAJ. 2018;190(11):E331-E333. DOI: 10.1503/cmaj.171292. (View with CPSBC or UBC)
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For women who have had a previous genital HPV-related lesion (such as high grade dysplasia or cancer of the cervix), is there a role in vaccination if they are age >45, to reduce risk of anal CA?
There are HPV tests available through the colposcopy service. They were available at some cost in Ontario in 2006 as a patient paid test, like screening PSA in BC.
This would be an interesting adjunct to screening for anal HPV as it would not take much special expertise to obtain samples.
Note that Pap testing in Ontario used a liquid and broom technique, which made addition of the HPV assessment a bit easier, likely not as easy with the brush and fixed slide used in B/C,