Factor, Stephanie H. MD MPH*; Cooperstein, Amy MPH†; Pereira, Guilherme A.‡; Goldstone, Stephen E. MD§
Anal squamous cell carcinoma cancer (ASCC) rates are rising with approximately 6000 cases in the United States in 2012 to more than 7000 cases projected in 2013 according to the National Cancer Registry’s Surveillance Epidemiology and End Results database.1,2 Although men who have sex with men (MSM) and immune-compromised individuals (HIV-infected, transplant recipients) are at greatest risk, rates have increased in all men and women, with the most rapid upswing beginning in 1997.3 Since then, according to the data from Surveillance Epidemiology and End Results, invasive anal cancer in males is increasing by 2.6% per year and in females by 2.0% per year,1 and carcinoma in situ is increasing in men and women by 14.2% per year.4
Both cervical and anal cancers are initiated when oncogenic human papillomaviruses (HPVs) infect the host cell. Persistent infection and possible integration into the host genome disturb normal protein transcription, which may lead to high-grade squamous intraepithelial lesions (HSILs) and potentially invasive cancer.5 Cervical cancer prevention includes routine cervical cytology screening via a Papanicolaou test, followed by colposcopy for patients with abnormal cells. Minimal standards for cervical colposcopy require the use of acetic acid and magnification to distinguish normal from abnormal tissue. Clinicians biopsy abnormal areas to identify HSIL and/or invasive cancer. When HSIL is found, it is treated by removal of the dysplastic region and the squamocolumnar transformation zone.4 Proper training in colposcopy is required for successful use. Rigorous screening in the United States has decreased the incidence of cervical cancer by 4.6% per year since the mid-1970s. The current rate is approximately 8/100,000 women.6
Similarly, advocates for ASCC prevention propose anal cytology screening (anal Papanicolaou test), followed by in-office high-resolution anoscopy (HRA) for patients found to have abnormal cells.7 High-resolution anoscopy is analogous to colposcopy and requires acetic acid to highlight potentially dysplastic squamous epithelium and magnification to observe vascular patterns and other abnormalities indicative of HSIL.8 Figure 1 illustrates the difference between examining the anal canal without magnification, with just acetic acid and using both acetic acid and magnification. Without acetic acid, flat HSIL is nearly impossible to find. Without magnification, it is impossible to determine if acetowhite areas contain abnormalities indicative of HSIL including coarse punctuation, atypical glands, and mosaicism. Abnormal areas are biopsied, and if HSIL is found, individual lesions are ablated under HRA guidance using a variety of techniques including infrared coagulation and electrocautery.9–12 Although there is no formal certification process, like colposcopy, HRA requires proper training and practice to master the necessary skill sets.8,13 Although there has never been a prospective study evaluating screening for and treatment of anal HSIL to prevent ASCC, multiple reports confirm decreased progression to cancer in treated patients when compared with those followed with a watch and wait approach.1–7,9–12,14–16 High-grade squamous intraepithelial lesion recurrence after treatment remains high, so repeated screening is required to prevent new lesions from developing and progressing to ASCC. High-resolution anoscopy for diagnosis and treatment of HSIL is best performed in-office where procedures are far less costly and burdensome to patients than when performed in an operating room (OR).
In addition to MSM and immune-compromised individuals, others at high risk for anal neoplasia and cancer include persons with a history of anal neoplasia and women with a history of HPV-associated disease (including cervical cancer, vulvar cancer, high-grade cervical intraepithelial neoplasia, or vulvar intraepithelial neoplasia).7,17 It is therefore likely that multiple medical specialties including HIV providers, gynecologists, sexually transmitted disease specialists, and colon and rectal surgeons treat patients at risk for anal cancer and could screen by performing anal Papanicolaou tests. Although no formal guidelines exist, based on a growing body of literature, patients with cytologic abnormalities should be sent to specialists trained in HRA for further evaluation. Although nonsurgeon specialists often perform HRA, patients with extensive anal dysplasia and condyloma require operative treatment by a surgeon. Colon and rectal surgeons often treat anorectal pathology including condyloma and anal cancer. They likely serve as a referral point for at-risk individuals and should play an important role in providing both anal Pap screening and HRA.
In 2008, the American Society of Colon and Rectal Surgeons (ASCRS), a voluntary membership society for surgeons interested in treating and studying colorectal diseases, issued practice parameters for anal squamous neoplasms.18 At that time, screening with anal cytology and ablating HSIL to prevent ASCC was given a third-tier recommendation because survival benefit had not been determined. In 2012, the ASCRS issued new practice parameters upgrading cytology and HSIL treatment to a first-tier recommendation.19
In 2005, the American Society for Colposcopy and Cervical Pathology first offered formal training courses in HRA. Among the growing numbers of providers who have been trained, there is a belief that HRA should become the standard of care for management of anal neoplasia. However, HRA and ablation of high-grade dysplasia to prevent cancer are not yet the standard of care as it is in the cervix. Since courses began relatively recently, it is clear that in comparison with the growing numbers of individuals affected by anal neoplasia, there is likely to be a paucity of expertly trained providers experienced in HRA to manage them. Although there are growing numbers of colon and rectal surgeons enrolling in the course, anecdotally, by specialty, they seem to make up less than one-fourth of attendees. Before the issuing of updated guidelines, we surveyed US ASCRS members to identify barriers to anal screening and interest in HRA training.
After approval from the Icahn School of Medicine at Mount Sinai Institutional Review Board and the ASCRS Executive Council, an e-mail was sent to all ASCRS members and fellows inviting them to participate via an Internet questionnaire administered through SurveyMonkey. Society members are licensed physicians in good standing and board certified in general surgery. Fellows are additionally board certified in colon and rectal surgery.
The survey assessed demographic data (sex, race, ethnicity, education, professional training, specialty), medical practice characteristics (type of practice, common conditions treated, procedures performed), patient population (age range, percent of patients who are MSM, are HIV infected, and have HPV-related disease), clinical practices (sexual history taking, anal dysplasia screening methods), and reasons for not screening. Most questions were multiple answer format (i.e., check all that apply). Participation was voluntary and could be terminated at any time. Participants were free to answer any questions and not required to submit results after initiating participation.
Clinicians were included in the analysis only if they were currently practicing physicians in the United States and they answered at least one of the following questions as “yes” or “no”: “Have you ever performed an anal Pap smear?” or “Have you ever performed high-resolution anoscopy?”
Characteristics associated with performing anal Papanicolaou test and HRA were studied separately. Univariable analyses using the χ2 test, Fisher exact test, and simple logistic regression were performed to find associations between characteristics assessed in the survey and anal screening. Characteristics with a P value of 0.20 or less in univariable analysis were evaluated for inclusion in the final multivariable logistic regression model. Evaluation for inclusion was done using manual and computer-assisted forward, backward, and stepwise multivariable logistic regression to identify those characteristics independently associated with the outcomes (performing anal Papanicolaou test and HRA). The final model included only those variable independently associated with these outcomes. A P value of 0.05 or less was considered statistically significant. All calculations were performed using SAS version 9.3 (SAS Institute Inc, Cary, NC). Not all questions were answered by all participants, and some questions referred to only certain segments of the cohort based on prior responses, so the “n” for each question was adjusted accordingly.
Between January and March 2012, 1655 ASCRS members were e-mailed the survey, of which 310 (19%) responded, 291 answered at least one of the qualifying questions, and 290 (18%) were practicing clinicians eligible for inclusion.
Most participants were white (83%), male (76%), and board-certified colon and rectal surgeons (89%) who graduated professional school after 1990 (54%) and worked within a group specialty practice (53%; Table 1). Comparing survey respondents with the basic demographics collected by the ASCRS on its membership, this study had a higher percentage of women (24% vs. 15%, P < 0.001), board-certified colon and rectal surgeons (89% vs. 76%, P = .01), and participants who graduated medical school before 1990 (50% vs. 37%, P < 0.001; Table 1).
Most study participants seemed well informed about risk factors for anal dysplasia and treat patients with anal dysplasia. Almost all study participants (99%) had read medical literature or attended a lecture (92%) on anal dysplasia. Most clinicians correctly acknowledged positive risk factors for anal dysplasia including MSM (88%), HIV-infected men (86%), women (73%), and those with history of anal condyloma (≈70%; data not shown). In addition, all (100%) participants treated patients at high risk for anal dysplasia: 100% treated HIV-infected patients and MSM, more than 95% of participants treated anal cancer and anal condyloma, and 92% treated anal dysplasia.
Despite their level of knowledge and practices, which include patients at risk for anal cancer, less than half conducted anal dysplasia screening. Of 290 participants, 140 (48%) performed at least one screening procedure: 96 (33%) performed an anal Papanicolaou test, whereas 99 (35%) of 286 participants performed HRA (Table 1).
Many who do collect anal cytology on their patients do so infrequently. Of 94 participants who perform anal cytology, 35 (37%) responded that they do it once a year or less, whereas slightly more than half (48 participants) do so more than once a year (Table 1). Fifty-eight participants perform both HRA and anal cytology, and of these, 16 (28%) perform anal cytology once a year or less.
Of those who do perform HRA, most do not perform HRA in the optimal setting, do not use the appropriate technique, and have not received appropriate training, with many having no intention of getting trained. Eight-three percent of the 99 who perform HRA primarily perform HRA in the OR, whereas 10% primarily perform HRA in-office. Only 82% of those performing HRA use the minimal necessary acetic acid with some form of magnification. Of 99 participants who perform HRA, 46 (46%) were formally trained. Forty-eight of 53 participants who perform HRA without having been trained answered a question regarding future training, and only 17 (35%) planned on becoming trained. Of 287 participants who responded that they evaluate patients in the OR for anal dysplasia by any method, 31% use acetic acid with some form of magnification, 37% use gross exam only, 23% use acetic acid without magnification, and 10% do not use any special technique for evaluation.
The importance of training in HRA was underappreciated by some participants. Of 53 participants who perform HRA without training, 52 answered the following question: “If you were never formally trained in HRA, what do you do if someone asks you to perform the procedure?” and 80% stated that they tell their patients they were never trained but still do HRA, whereas 4% tell patients HRA is not necessary (Table 1).
Participants who do not screen were asked to provide one or more reasons for not performing the procedures, and 125 responded stating they were never formally trained (52%), did not think it was a priority (23%), and did not believe there was enough evidence to support it (21%). Close to 20% responded affirmatively to each of the following: they did not want it to take over their practice and would refer patients to another practitioner for screening. Only 8% were concerned about cost to the patient (Table 1). Although all participants reported treating patients at high risk for anal neoplasia, 24 (19%) participants stated they did not screen because they did see patients who need it.
After univariable and multivariable analyses of all characteristics with P ≤ 0.20 in univariable analysis, the final multivariable regression model found that performing anal Papanicolaou tests was statistically associated with being female (adjusted odds ratio [AOR], 1.96; 95% confidence interval [CI], 1.01–3.84]), African American race (AOR, 8.31; 95% CI, 1.17–59.12), taking a sexual history 1 or more times per year (AOR, 3.99; 95% CI, 1.28, 12.48), treating patients with sexually transmitted infections (AOR, 1.86; 95% CI, 1.00–3.46), and having most patients 35 to 44 years old (AOR, 2.42; 95% CI, 0.99–5.90). When compared with participants whose practices contain less than 1% HIV-infected patients, treating more HIV-infected patients significantly increased the likelihood the participants performed anal Papanicolaou tests (1%–5% HIV infected [AOR, 2.70; 95% CI, 1.26–5.80] and >5% HIV infected [AOR, 6.13; 95% CI, 2.13–17.68]; Table 2).
After univariable and multivariable analyses of all characteristics with P ≤ 0.20 in univariable analysis, the final multivariable regression model found that performing HRA was statistically associated with more recent year of professional school graduation (AOR, 1.04 per year; 95% CI, 1.01–1.06), having 1% to 5% HIV-infected patients compared with having less than 1% HIV-infected patients (AOR, 2.55; 95% CI, 1.25–5.23), and having more than 5% HIV-infected patients when compared with less than 1% (AOR, 4.22%; 95% CI, 1.6–11.15; Table 3).
Most study participants seemed well informed about risk factors for anal dysplasia and treat patients with anal dysplasia. Despite their level of knowledge and caring for an at-risk patient population, less than half conducted anal screening, and many believe that screening is not worthwhile. Of those who perform HRA, only a small subset was formally trained and use the minimally required technique of acetic acid and magnification compromising the sensitivity and specificity of HRA, as well as the ability to determine cancer prevention. If clinicians perform HRA without the proper tools or training, lesions can be missed, and patients are left with a false sense of security that they do not have HSIL.
Practitioners in many specialties are likely to screen for anal cancer and need to identify clinicians to whom patients with abnormal anal Papanicolaou test results should be referred. Colon and rectal surgeons are best able to treat both limited and extensive diseases and, as such, are a likely referral choice. This study, however, provides invaluable information in pointing out that many colon and rectal surgeons either do not perform HRA or, if they do, were never formally trained and could use inadequate technique. Specifically, practitioners referring patients for HRA should determine if the surgeon has been formally trained in HRA and where the practitioner performs the HRA procedure. Referring physicians will best serve their patients by referral to trained practitioners who perform HRA in office where it is most cost-effective and comfortable for patients. Moreover, in order for skill sets to develop fully, procedures must be practiced regularly because there is a steep learning curve.13 With more than one-fourth of respondents who perform both HRA and anal cytology obtaining cytology once a year or less, it seems that either most respondents do not follow their patients after HRA or, if they do, then they do not adhere to recommended follow-up guidelines.7,10,11
Although a referring physician may have more options finding trained practitioners in many different specialties who can perform office-based HRA, their patients with the most severe disease requiring treatment in an OR will still require a surgeon’s skill. However, of respondents who treat anal HPV-related disease in the OR even without HRA, only one-third use acetic acid and magnification, thereby making it difficult to find a surgeon who can truly evaluate a patient for high-grade dysplasia and superficially invasive anal cancer that has not yet developed mass effect.
For public health practitioners interested in the widespread practice of appropriate anal dysplasia screening and diagnosis, this study suggests that lack of universal anal dysplasia screening is not due to lack of knowledge about the at-risk groups but due to the perceived lack of medical evidence to support the practice. Although a randomized clinical trial demonstrating the efficacy of anal screening would provide the best evidence of the importance of anal screening, no such trials are currently funded. Educational programs highlighting the best interpretation of the available studies may be able to address this perceived lack of evidence in the absence of clinical trials. This study also suggests that lack of correct technique among those who do practice HRA is due to lack of formal training. Outreach to surgeons about the importance of formal training and widespread availability of training programs as well as ways to implement screening techniques into an office setting that will not become disruptive or over burdensome are recommended. Finally, if we are to improve anal dysplasia screening among colon and rectal surgeons, this study provides invaluable information regarding which surgeons will potentially be most receptive to adopting screening practices including women, African American surgeons, more recent graduates, and those with a higher percentage of HIV-infected patients in their practices. It is also critical that outreach targets colon and rectal surgeons already performing HRA-absent proper technique or training.
The major strength of this study is that it is the first to examine anal dysplasia clinical practice among colon and rectal surgeons in the United States. There is only one other study that has evaluated anal dysplasia screening. Three hundred ninety-three members of coloproctology societies in Europe, Australia, and New Zealand responded to an Internet survey.20 Of respondents in that study, 42% used acetic acid (23% in conjunction with HRA) and 20% performed cytology. Our results are similar to their findings providing some validation for the results of both studies.
A weakness of this study is that our data were collected before the publication of the most recent ASCRS practice parameters recommending screening for and ablation of HSIL.19 It is possible that more surgeons now desire training in HRA and/or may have already started screening. Other weaknesses include the fact that less than one-fourth of ASCRS members participated in this study, and it is impossible to tell if respondents’ knowledge and practice are different from those of the membership as a whole. Finally, the data collected are cross sectional, which prevents us from determining cause and effect for factors such as whether or not having a higher percentage of patients with HIV, treating sexually transmitted infections, taking a sexual history, and seeing patients aged 35 to 44 years motivated clinicians to begin screening or if patients with these characteristics/needs sought out clinicians offering screening. Further study is necessary to address these limitations and to determine whether our findings are generalizable to other clinician specialists treating patients at risk for ASCC.
Many ASCRS member respondents to this survey do not screen for anal dysplasia. Those that do are often not formally trained and use inadequate technique. More training and research must be performed before the new ASCRS practice parameters translate into clinical practice. It is important to check a clinician’s training and experience in HRA before referring a patient for the procedure.
1. American Cancer Society. Cancer Facts & Figures 2013
. Atlanta; 2013.
3. Nelson RA, Levine AM, Bernstein L, et al. Changing patterns of anal canal carcinoma in the United States. J Clin Oncol 2013; 31: 1569–1575.
4. Apgar BS, Kittendorf AL, Bettcher CM, et al. Update on ASCCP consensus guidelines for abnormal cervical screening tests and cervical histology. Am Fam Phys 2009; 80: 147–155.
5. Clark MA, Hartley A, Geh JI. Cancer of the anal canal. Lancet Oncol 2004; 5: 149–157.
6. Howlader N, Noone AM, Krapcho M. SEER Cancer Statistics Review, 1975–2010 [Online]. Bethesda, MD: National Cancer Institute.
7. Goldstone SE, Winkler B, Ufford LJ, et al. High prevalence of anal squamous intraepithelial lesions and squamous-cell carcinoma in men who have sex with men as seen in a surgical practice. Dis Colon Rectum 2001; 44: 690–698.
8. Jay N, Berry JM, Hogeboom CJ, et al. Colposcopic appearance of anal squamous intraepithelial lesions: relationship to histopathology. Dis Colon Rectum 1997; 40: 919–928.
9. Goldstone RN, Goldstone AB, Russ J, et al. Long-term follow-up of infrared coagulator ablation of anal high-grade dysplasia in men who have sex with men. Dis Colon Rectum 2011; 54: 1284–1292.
10. Marks DK, Goldstone SE. Electrocautery ablation of high-grade anal squamous intraepithelial lesions in HIV-negative and HIV-positive men who have sex with men. J Acquir Immune Defic Syndr 2012; 59: 259–265.
11. Pineda CE, Berry JM, Jay N, et al. High-resolution anoscopy targeted surgical destruction of anal high-grade squamous intraepithelial lesions: A ten-year experience. Dis Colon Rectum 2008; 51: 829–835; discussion 835–837.
12. Weis SE, Vecino I, Pogoda JM, et al. Treatment of high-grade anal intraepithelial neoplasia with infrared coagulation in a primary care population of HIV-infected men and women. Dis Colon Rectum 2012; 55: 1236–1243.
13. Swedish KA, Lee EQ, Goldstone SE. The changing picture of high-grade anal intraepithelial neoplasia in men who have sex with men: The effects of 10 years of experience performing high-resolution anoscopy. Dis Colon Rectum 2011; 54: 1003–1007.
14. Devaraj B, Cosman BC. Expectant management of anal squamous dysplasia in patients with HIV. Dis Colon Rectum 2006; 49: 36–40.
15. Watson AJM, Smith BB, Whitehead MR, et al. Malignant progression of anal intra-epithelial neoplasia. A N Z J Surg 2006; 76: 715–717.
16. Scholefield JH, Castle MT, Watson NFS. Malignant transformation of high-grade anal intraepithelial neoplasia. British J Surg 2005; 92: 1133–1136.
17. Saleem AM, Paulus JK, Shapter AP, et al. Risk of anal cancer in a cohort with human papillomavirus–related gynecologic neoplasm. Obstetrics and Gynecology 2011; 117: 643–649.
18. Fleshner PR, Chalasani S, Chang GJ, et al. Practice parameters for anal squamous neoplasms. Dis Colon Rectum 2008; 51: 2–9.
19. Steele SR, Varma MG, Melton GB, et al. Practice parameters for anal squamous neoplasms. Dis Colon Rectum 2012; 55: 735–749.
20. Dindo D, Nocito A, Schettle M, et al. What should we do about anal condyloma and anal intraepithelial neoplasia? Results of a survey. Colorectal Disease 2011; 13: 796–801.