- Email: [email protected]
Incorporating anal dysplasia screening and management into a surgical practice
Author’s Accepted Manuscript Incorporating anal dysplasia screening management into a surgical practice
and
Mark Lane Welton, Amy L. Lightner
www.elsevier.com/locate/yscrs
PII: DOI: Reference:
S1043-1489(17)30021-0 http://dx.doi.org/10.1053/j.scrs.2017.04.011 YSCRS595
To appear in: Seminars in Colon and Rectal Surgery Cite this article as: Mark Lane Welton and Amy L. Lightner, Incorporating anal dysplasia screening and management into a surgical practice, Seminars in Colon and Rectal Surgery, http://dx.doi.org/10.1053/j.scrs.2017.04.011 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Incorporating anal dysplasia screening and management into a surgical practice Mark Lane Welton, MD, MHCM and Amy L. Lightner, MD
Mark Lane Welton, MD, MHCM Harry A. Oberhelman Jr., Professor & Chair, Colon & Rectal Surgery Stanford University School of Medicine Chief of Staff, Stanford Hospital & Clinics Associate Chief Medical Officer and Medical Director, Hospital Operations Center Stanford CA and Amy L. Lightner, MD Assistant Professor of Surgery, Mayo Clinic College of Medicine Senior Associate Consultant, Department of Surgery, Mayo Clinic College of Medicine, Division of Colon and Rectal Surgery Mayo Clinic Rochester MN
Mailing Address: Mark Lane Welton, MD, MHCM ROOM H3105, MC 5328 300 Pasteur Drive, Stanford CA 94305
Abstract: Screening practices for anal dysplasia with the use of anal cytology and high-resolution anoscopy (HRA) has become a topic of increased interest to colon and rectal surgeons. However, screening continues to be practiced by a minority of clinicians. One major hurdle is how to incorporate anal cytology screening programs into busy colorectal surgical practices. In this article I highlight my early experience treating anal dysplasia and review my current approach and practice pattern for treating anal dysplasia. I also suggest a few paradigms for implementing screening into various clinical settings, and offer surveillance algorithms for individual patients with anal dysplasia based on risk factors.
Key Words: high resolution anoscopy, anal cytology, anal dysplasia
Introduction Over the past 20 years, I have noticed that the treatment of anal dysplasia has gained increasing acceptance. Conversations with colleagues have transitioned from “you’re not really doing that” to “how do you do that”. But this has been a slow evolution and a work in progress. My first eight years in practice, spent at University of California, San Francisco (UCSF), was not representative of most people’s practices. Thus, my treatment algorithms were not applicable to many other colon and rectal surgeons. At UCSF, we had a significant proportion of men who were at increased risk due to sexual practices, immune status and or drug usage, with large volume disease, who were willing to participate in an active clinical management program. I was the downstream treating surgeon. I saw the worst cases – those with circumferential or near circumferential high-grade disease, those with extensive large volume condylomatous disease, or those with complicated anorectal anatomy or pathology that made treatment in the office impossible. I had the luxury of working with two non-surgical physicians and a nurse practitioner, who were treating these patients preoperatively. We all worked together in the operating room relying heavily on the teachings of our nurse practitioner, Naomi Jay, making decisions about what should be treated, what could safely be treated and what should be treated at a later date. (1) While I controlled the cautery and extent of tissue destruction, they were there for a collaborative effort to provide longitudinal care to the patient. Postoperatively, it was these physicians and NP who managed the patients with follow up anal cytology and high-resolution anoscopy (HRA), as indicated Now at Stanford, with a different patient population, I have a much different practice. More patients are immunocompetent heterosexuals not engaged in high-risk behaviors. More
patients are referred with LSIL/HSIL after colonoscopic biopsies of “polyps” in the rectum. Finally, there is a population of undergraduate and graduate students, and young professionals who present with anal condylomata and a variety of risk factors, who like many young individuals, do not have established health care providers for follow up. Sweeping statements about how to incorporate anal dysplasia screening and management into a colon and rectal surgeon’s practice are often overwhelming and impractical. Rather, the best approach is to define the screening and treatment algorithms based on patient and practice factors. Patient factors include gender, sexual practices, immune status, age, and history of a previous lower anogenital tract HPV infection.(2-7) Practice factors to consider are the proportion of high risk patients, availability of nearby supporting clinical practices, and the type of colon and rectal surgical practice. If your practice is in a region with a high volume of at risk patients, there are a couple options. One is to have a dysplasia clinic within your colon and rectal surgery office. The clinic can by tailored to occupy as much of the practice time as you desire. Advanced practice providers (APP) can perform both the initial and follow up anal cytology sampling, and the diagnostic, surveillance and therapeutic HRA in the clinic/office setting.(8) This allows the colon and rectal surgeon to limit their practice to those lesions requiring treatment in the operating room. The operations can be performed in the outpatient setting with or without conscious sedation. The second option is to partner with a HIV positive care clinic or a practice group that performs anal cytology screening. The clinicians at the partnering clinic may perform the initial and follow up screening exams, but refer patients needing operative intervention to your office.
Low volume regions provide a different set of challenges that are also best addressed in an individualized fashion. Initial screening might be done in the office by an APP that is active in other portions of the surgeon’s practice, in a HIV-positive care clinic, or in a gynecology office. Or, the colorectal surgeon may perform anal cytology and HRA themselves. As with the highvolume practices, HRA for treatment may be performed in the office or the operating room. My preference is to treat patients with extensive disease in an ambulatory surgery center under conscious sedation. I feel it allows visualization of the distal rectal mucosa and bases of hemorrhoidal cushions that simply cannot be achieved with a plastic anoscope in an awake patient. With experienced anesthesiologists and nurses, the procedure takes an average of 12 minutes. In cases of extensive disease, it may take up to 20 minutes. In the operating room the patient is positioned prone jackknife and the buttocks are taped apart.(9) After intravenous conscious sedation is provided, a local block is delivered with 0.25% Marcaine in the subcutaneous tissue and 0.5% Marcaine with 1:200,000 epinephrine into the sphincter complex. The anal canal and perianal skin are soaked with 3% vinegar while the operative microscope is brought into position. A medium Hill Ferguson provides exposure of the anal canal and distal rectum. The perianal skin, anal mucosa and distal rectal mucosa are visualized through the operative microscope. Lesions that are concerning for HSIL are biopsied and destroyed. Sample biopsies of condylomatous lesions are taken and those lesions are destroyed with electocautery. Turnover times have dropped to 10-15 leaving this as the most efficient means to treat patients who need treatment of extensive or complicated disease. Although we do report recurrences with this approach, I would highlight that 77% of the recurrences are treated in the office with either trichloracetic acid or ablative therapy. (10) In
general, most patients returning to the operating room are those with circumferential disease who benefit from a staged approach to prevent anal stenosis, or require the intravenous sedation.(11) Following surgery, patients need to be followed. But the question remains: how frequently and aggressively? This is one of the biggest challenges in the overall management of these patients. As with colorectal cancer, it seems reasonable to risk stratify patients, and modify the surveillance algorithm accordingly. Based on the current literature, I recommend surveillance as outlined:
HIV positive and negative men who have receptive anal intercourse and are over the age of 35-40 – at least annual anal cytology, anorectal exam and anoscopy. HRA for ASCUS or “worse”.
HIV positive women over the age of 35-40 – at least annual anal cytology, anorectal exam and anoscopy. HRA for ASCUS or “worse”.
Men and women over the age of 35-40 who are immunosuppressed by medication or disease other than HIV who engage in anoreceptive intercourse – at least annual anal cytology, anorectal exam and anoscopy. HRA for ASCUS or “worse”.
Men and women immunosuppressed by medication or disease other than HIV who do not self report anoreceptive intercourse without a history of oral or lower anogenital tract HPV infection – consider initial HPV mRNA testing and follow with annual anal cytology, anorectal exam and HRA if positive.
Women with a history of lower anogenital tract neoplasia – annual anal cytology, anorectal exam and anoscopy. HRA for ASCUS or “worse”.
Immunocompetent men and women 50 years of age and older with an incidental “rectal polyp” found on colonoscopy that is AIN I or AIN III – HRA and follow up anal cytology at one year.
Young immunocompetent men and women without risk factors for anal cancer and a history of uncomplicated anal condylomatous disease – symptom directed anorectal exam and anoscopy.
The challenge with these proposed guidelines are the same limitations seen in all guidelines – applicability to a variety patient populations as well as lack of concrete evidence from large trials. How do we account for the monogamous man who has been having sex with the same man for the last 40-years? Certainly, he is not at the same risk and does not require the same surveillance as the 40-year-old man who has had exposure to both multiple partners and illicit drugs Further, not all immunosuppression appears to be the same.
Immunosuppression associated with kidney transplant seems to be different than that associated with immunosuppression for treatment of inflammatory bowel disease.(12-14) Finally, what does the impact of age have on screening and surveillance? When do we stop and what do we stop? Can we stop anal cytology at a certain age and simply perform anorectal and anoscopic exams? HPV subtyping in HIV positive and negative men who have sex with men is of questionable value. This is due to the high prevalence of high-risk types. On the other hand, HPV subtyping in low risk patients (e.g. women with a history of cervical neoplasia or men and women with a history of anal condyloma) may be helpful in directing ongoing surveillance.(15) Currently I only perform HPV subtyping when requested by the patient. Some have suggested that anal cytology and HRA be routinely used in follow up of patients with anal cancer.(16) However, I question its utility when looking at the number of patients it might actually benefit. According to the SEER data, 48% of patients with anal cancer initially present with localized disease, and survival in this group is 80%.(17) The other 20% of patients die from persistent or recurrent disease. Since the nature of the failures – persistence versus recurrence – is not defined and the location of the failures – local, regional, distant – is unknown in patients presenting with localized disease, the benefit of anal cytology over simple digital rectal exam and anoscopy remains unclear. In summary, anal dysplasia screening and management may easily be incorporated into the practice of a colorectal surgeon. I have suggested models of incorporation based on patient and practice patterns, and have proposed surveillance algorithms based on the patient’s risk profile. While many continue to advocate a watchful waiting approach, I continue to favor
targeted intervention and tailored follow up given the favorable rates of progression that we have been able to demonstrate with this approach and the documented progression of untreated lesions.(2,10) References: 1. Jay N, Berry JM, Hogeboom CJ, et al. Colposcopic appearance of anal squamous intraepithelial lesions: relationship to histopathology. Dis Colon Rectum. 1997;40(8):919-28. 2. Berry JM, Jay N, Cranston RD, et al. Progression of anal high-grade squamous intraepithelial lesions to invasive anal cancer among HIV-infected men who have sex with men. Int J Cancer. 2014;134(5):1147-55. 3. Burgos J, Curran A, Tallada N, et al. Risk of progression to high-grade anal intraepithelial neoplasia in HIV-infected MSM. AIDS. 2015;29(6):695-702. 4. Cronin B, Bregar A, Luis C, et al. Evaluation of anal cytology and dysplasia in women with a history of lower genital tract dysplasia and malignancy. Gynecol Oncol. 5. Gandra S, Azar A, Wessolossky M. Anal high-risk human papillomavirus infection and high-grade anal intraepithelial neoplasia detected in women and heterosexual men infected with human immunodeficiency virus. HIV AIDS (Auckl). 2015;7:29-34. 6. Moscicki AB, Darragh TM, Berry-Lawhorn JM, et al. Screening for Anal Cancer in Women. J Low Genit Tract Dis. 2015;19(3 Suppl 1):S27-42. 7. Robison K, Cronin B, Bregar A, et al. Anal Cytology and Human Papillomavirus Genotyping in Women With a History of Lower Genital Tract Neoplasia Compared With Low-Risk Women. Obstet Gynecol. 2015;126(6):1294-300. 8. Patel J, Salit IE, Berry MJ, de Pokomandy A, Nathan M, Fishman F, et al. Environmental scan of anal cancer screening practices: worldwide survey results. Cancer Med. 2014;3(4):1052-61. 9. Pineda CE, Berry JM, Welton ML. High resolution anoscopy and targeted treatment of high-grade squamous intraepithelial lesions. Dis Colon Rectum. 2006;49(1):126. 10. Pineda CE, Berry JM, Jay N, Palefsky JM, Welton ML. High-resolution anoscopy targeted surgical destruction of anal high-grade squamous intraepithelial lesions: a ten-year experience. Dis Colon Rectum. 2008;51(6):829-35; discussion 35-7. 11. Pineda CE, Berry JM, Jay N, Palefsky JM, Welton ML. High resolution anoscopy in the planned staged treatment of anal squamous intraepithelial lesions in HIV-negative patients. J Gastrointest Surg. 2007;11(11):1410-5; discussion 5-6. 12. Ogilvie JW, Jr., Park IU, Downs LS, Anderson KE, Hansberger J, Madoff RD. Anal dysplasia in kidney transplant recipients. J Am Coll Surg. 2008;207(6):914-21. 13. Patel HS, Silver AR, Levine T, Williams G, Northover JM. Human
papillomavirus infection and anal dysplasia in renal transplant recipients. Br J Surg. 2010;97(11):1716-21. 14. Shah SB, Pickham D, Araya H, Kamal A, Pineda CE, Ghole S, et al. Prevalence of Anal Dysplasia in Patients With Inflammatory Bowel Disease. Clin Gastroenterol Hepatol. 2015;13(11):1955-61 e1. 15. Robison K, Cronin B, Bregar A, Luis C, DiSilvestro P, Schechter S, et al. Anal Cytology and Human Papillomavirus Genotyping in Women With a History of Lower Genital Tract Neoplasia Compared With Low-Risk Women. Obstet Gynecol. 2015;126(6):1294-300. 16. Goon P, Morrison V, Fearnhead N, Davies J, Wilson C, Jephcott C, et al. High resolution anoscopy may be useful in achieving reductions in anal cancer local disease failure rates. Eur J Cancer Care (Engl). 2015;24(3):4116. 17. SEER NCI. SEER Stat Fact Sheets: Anal Cancer. 2016; Available from: http://seer.cancer.gov/statfacts/html/anus.html.
and
Mark Lane Welton, Amy L. Lightner
www.elsevier.com/locate/yscrs
PII: DOI: Reference:
S1043-1489(17)30021-0 http://dx.doi.org/10.1053/j.scrs.2017.04.011 YSCRS595
To appear in: Seminars in Colon and Rectal Surgery Cite this article as: Mark Lane Welton and Amy L. Lightner, Incorporating anal dysplasia screening and management into a surgical practice, Seminars in Colon and Rectal Surgery, http://dx.doi.org/10.1053/j.scrs.2017.04.011 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Incorporating anal dysplasia screening and management into a surgical practice Mark Lane Welton, MD, MHCM and Amy L. Lightner, MD
Mark Lane Welton, MD, MHCM Harry A. Oberhelman Jr., Professor & Chair, Colon & Rectal Surgery Stanford University School of Medicine Chief of Staff, Stanford Hospital & Clinics Associate Chief Medical Officer and Medical Director, Hospital Operations Center Stanford CA and Amy L. Lightner, MD Assistant Professor of Surgery, Mayo Clinic College of Medicine Senior Associate Consultant, Department of Surgery, Mayo Clinic College of Medicine, Division of Colon and Rectal Surgery Mayo Clinic Rochester MN
Mailing Address: Mark Lane Welton, MD, MHCM ROOM H3105, MC 5328 300 Pasteur Drive, Stanford CA 94305
Abstract: Screening practices for anal dysplasia with the use of anal cytology and high-resolution anoscopy (HRA) has become a topic of increased interest to colon and rectal surgeons. However, screening continues to be practiced by a minority of clinicians. One major hurdle is how to incorporate anal cytology screening programs into busy colorectal surgical practices. In this article I highlight my early experience treating anal dysplasia and review my current approach and practice pattern for treating anal dysplasia. I also suggest a few paradigms for implementing screening into various clinical settings, and offer surveillance algorithms for individual patients with anal dysplasia based on risk factors.
Key Words: high resolution anoscopy, anal cytology, anal dysplasia
Introduction Over the past 20 years, I have noticed that the treatment of anal dysplasia has gained increasing acceptance. Conversations with colleagues have transitioned from “you’re not really doing that” to “how do you do that”. But this has been a slow evolution and a work in progress. My first eight years in practice, spent at University of California, San Francisco (UCSF), was not representative of most people’s practices. Thus, my treatment algorithms were not applicable to many other colon and rectal surgeons. At UCSF, we had a significant proportion of men who were at increased risk due to sexual practices, immune status and or drug usage, with large volume disease, who were willing to participate in an active clinical management program. I was the downstream treating surgeon. I saw the worst cases – those with circumferential or near circumferential high-grade disease, those with extensive large volume condylomatous disease, or those with complicated anorectal anatomy or pathology that made treatment in the office impossible. I had the luxury of working with two non-surgical physicians and a nurse practitioner, who were treating these patients preoperatively. We all worked together in the operating room relying heavily on the teachings of our nurse practitioner, Naomi Jay, making decisions about what should be treated, what could safely be treated and what should be treated at a later date. (1) While I controlled the cautery and extent of tissue destruction, they were there for a collaborative effort to provide longitudinal care to the patient. Postoperatively, it was these physicians and NP who managed the patients with follow up anal cytology and high-resolution anoscopy (HRA), as indicated Now at Stanford, with a different patient population, I have a much different practice. More patients are immunocompetent heterosexuals not engaged in high-risk behaviors. More
patients are referred with LSIL/HSIL after colonoscopic biopsies of “polyps” in the rectum. Finally, there is a population of undergraduate and graduate students, and young professionals who present with anal condylomata and a variety of risk factors, who like many young individuals, do not have established health care providers for follow up. Sweeping statements about how to incorporate anal dysplasia screening and management into a colon and rectal surgeon’s practice are often overwhelming and impractical. Rather, the best approach is to define the screening and treatment algorithms based on patient and practice factors. Patient factors include gender, sexual practices, immune status, age, and history of a previous lower anogenital tract HPV infection.(2-7) Practice factors to consider are the proportion of high risk patients, availability of nearby supporting clinical practices, and the type of colon and rectal surgical practice. If your practice is in a region with a high volume of at risk patients, there are a couple options. One is to have a dysplasia clinic within your colon and rectal surgery office. The clinic can by tailored to occupy as much of the practice time as you desire. Advanced practice providers (APP) can perform both the initial and follow up anal cytology sampling, and the diagnostic, surveillance and therapeutic HRA in the clinic/office setting.(8) This allows the colon and rectal surgeon to limit their practice to those lesions requiring treatment in the operating room. The operations can be performed in the outpatient setting with or without conscious sedation. The second option is to partner with a HIV positive care clinic or a practice group that performs anal cytology screening. The clinicians at the partnering clinic may perform the initial and follow up screening exams, but refer patients needing operative intervention to your office.
Low volume regions provide a different set of challenges that are also best addressed in an individualized fashion. Initial screening might be done in the office by an APP that is active in other portions of the surgeon’s practice, in a HIV-positive care clinic, or in a gynecology office. Or, the colorectal surgeon may perform anal cytology and HRA themselves. As with the highvolume practices, HRA for treatment may be performed in the office or the operating room. My preference is to treat patients with extensive disease in an ambulatory surgery center under conscious sedation. I feel it allows visualization of the distal rectal mucosa and bases of hemorrhoidal cushions that simply cannot be achieved with a plastic anoscope in an awake patient. With experienced anesthesiologists and nurses, the procedure takes an average of 12 minutes. In cases of extensive disease, it may take up to 20 minutes. In the operating room the patient is positioned prone jackknife and the buttocks are taped apart.(9) After intravenous conscious sedation is provided, a local block is delivered with 0.25% Marcaine in the subcutaneous tissue and 0.5% Marcaine with 1:200,000 epinephrine into the sphincter complex. The anal canal and perianal skin are soaked with 3% vinegar while the operative microscope is brought into position. A medium Hill Ferguson provides exposure of the anal canal and distal rectum. The perianal skin, anal mucosa and distal rectal mucosa are visualized through the operative microscope. Lesions that are concerning for HSIL are biopsied and destroyed. Sample biopsies of condylomatous lesions are taken and those lesions are destroyed with electocautery. Turnover times have dropped to 10-15 leaving this as the most efficient means to treat patients who need treatment of extensive or complicated disease. Although we do report recurrences with this approach, I would highlight that 77% of the recurrences are treated in the office with either trichloracetic acid or ablative therapy. (10) In
general, most patients returning to the operating room are those with circumferential disease who benefit from a staged approach to prevent anal stenosis, or require the intravenous sedation.(11) Following surgery, patients need to be followed. But the question remains: how frequently and aggressively? This is one of the biggest challenges in the overall management of these patients. As with colorectal cancer, it seems reasonable to risk stratify patients, and modify the surveillance algorithm accordingly. Based on the current literature, I recommend surveillance as outlined:
HIV positive and negative men who have receptive anal intercourse and are over the age of 35-40 – at least annual anal cytology, anorectal exam and anoscopy. HRA for ASCUS or “worse”.
HIV positive women over the age of 35-40 – at least annual anal cytology, anorectal exam and anoscopy. HRA for ASCUS or “worse”.
Men and women over the age of 35-40 who are immunosuppressed by medication or disease other than HIV who engage in anoreceptive intercourse – at least annual anal cytology, anorectal exam and anoscopy. HRA for ASCUS or “worse”.
Men and women immunosuppressed by medication or disease other than HIV who do not self report anoreceptive intercourse without a history of oral or lower anogenital tract HPV infection – consider initial HPV mRNA testing and follow with annual anal cytology, anorectal exam and HRA if positive.
Women with a history of lower anogenital tract neoplasia – annual anal cytology, anorectal exam and anoscopy. HRA for ASCUS or “worse”.
Immunocompetent men and women 50 years of age and older with an incidental “rectal polyp” found on colonoscopy that is AIN I or AIN III – HRA and follow up anal cytology at one year.
Young immunocompetent men and women without risk factors for anal cancer and a history of uncomplicated anal condylomatous disease – symptom directed anorectal exam and anoscopy.
The challenge with these proposed guidelines are the same limitations seen in all guidelines – applicability to a variety patient populations as well as lack of concrete evidence from large trials. How do we account for the monogamous man who has been having sex with the same man for the last 40-years? Certainly, he is not at the same risk and does not require the same surveillance as the 40-year-old man who has had exposure to both multiple partners and illicit drugs Further, not all immunosuppression appears to be the same.
Immunosuppression associated with kidney transplant seems to be different than that associated with immunosuppression for treatment of inflammatory bowel disease.(12-14) Finally, what does the impact of age have on screening and surveillance? When do we stop and what do we stop? Can we stop anal cytology at a certain age and simply perform anorectal and anoscopic exams? HPV subtyping in HIV positive and negative men who have sex with men is of questionable value. This is due to the high prevalence of high-risk types. On the other hand, HPV subtyping in low risk patients (e.g. women with a history of cervical neoplasia or men and women with a history of anal condyloma) may be helpful in directing ongoing surveillance.(15) Currently I only perform HPV subtyping when requested by the patient. Some have suggested that anal cytology and HRA be routinely used in follow up of patients with anal cancer.(16) However, I question its utility when looking at the number of patients it might actually benefit. According to the SEER data, 48% of patients with anal cancer initially present with localized disease, and survival in this group is 80%.(17) The other 20% of patients die from persistent or recurrent disease. Since the nature of the failures – persistence versus recurrence – is not defined and the location of the failures – local, regional, distant – is unknown in patients presenting with localized disease, the benefit of anal cytology over simple digital rectal exam and anoscopy remains unclear. In summary, anal dysplasia screening and management may easily be incorporated into the practice of a colorectal surgeon. I have suggested models of incorporation based on patient and practice patterns, and have proposed surveillance algorithms based on the patient’s risk profile. While many continue to advocate a watchful waiting approach, I continue to favor
targeted intervention and tailored follow up given the favorable rates of progression that we have been able to demonstrate with this approach and the documented progression of untreated lesions.(2,10) References: 1. Jay N, Berry JM, Hogeboom CJ, et al. Colposcopic appearance of anal squamous intraepithelial lesions: relationship to histopathology. Dis Colon Rectum. 1997;40(8):919-28. 2. Berry JM, Jay N, Cranston RD, et al. Progression of anal high-grade squamous intraepithelial lesions to invasive anal cancer among HIV-infected men who have sex with men. Int J Cancer. 2014;134(5):1147-55. 3. Burgos J, Curran A, Tallada N, et al. Risk of progression to high-grade anal intraepithelial neoplasia in HIV-infected MSM. AIDS. 2015;29(6):695-702. 4. Cronin B, Bregar A, Luis C, et al. Evaluation of anal cytology and dysplasia in women with a history of lower genital tract dysplasia and malignancy. Gynecol Oncol. 5. Gandra S, Azar A, Wessolossky M. Anal high-risk human papillomavirus infection and high-grade anal intraepithelial neoplasia detected in women and heterosexual men infected with human immunodeficiency virus. HIV AIDS (Auckl). 2015;7:29-34. 6. Moscicki AB, Darragh TM, Berry-Lawhorn JM, et al. Screening for Anal Cancer in Women. J Low Genit Tract Dis. 2015;19(3 Suppl 1):S27-42. 7. Robison K, Cronin B, Bregar A, et al. Anal Cytology and Human Papillomavirus Genotyping in Women With a History of Lower Genital Tract Neoplasia Compared With Low-Risk Women. Obstet Gynecol. 2015;126(6):1294-300. 8. Patel J, Salit IE, Berry MJ, de Pokomandy A, Nathan M, Fishman F, et al. Environmental scan of anal cancer screening practices: worldwide survey results. Cancer Med. 2014;3(4):1052-61. 9. Pineda CE, Berry JM, Welton ML. High resolution anoscopy and targeted treatment of high-grade squamous intraepithelial lesions. Dis Colon Rectum. 2006;49(1):126. 10. Pineda CE, Berry JM, Jay N, Palefsky JM, Welton ML. High-resolution anoscopy targeted surgical destruction of anal high-grade squamous intraepithelial lesions: a ten-year experience. Dis Colon Rectum. 2008;51(6):829-35; discussion 35-7. 11. Pineda CE, Berry JM, Jay N, Palefsky JM, Welton ML. High resolution anoscopy in the planned staged treatment of anal squamous intraepithelial lesions in HIV-negative patients. J Gastrointest Surg. 2007;11(11):1410-5; discussion 5-6. 12. Ogilvie JW, Jr., Park IU, Downs LS, Anderson KE, Hansberger J, Madoff RD. Anal dysplasia in kidney transplant recipients. J Am Coll Surg. 2008;207(6):914-21. 13. Patel HS, Silver AR, Levine T, Williams G, Northover JM. Human
papillomavirus infection and anal dysplasia in renal transplant recipients. Br J Surg. 2010;97(11):1716-21. 14. Shah SB, Pickham D, Araya H, Kamal A, Pineda CE, Ghole S, et al. Prevalence of Anal Dysplasia in Patients With Inflammatory Bowel Disease. Clin Gastroenterol Hepatol. 2015;13(11):1955-61 e1. 15. Robison K, Cronin B, Bregar A, Luis C, DiSilvestro P, Schechter S, et al. Anal Cytology and Human Papillomavirus Genotyping in Women With a History of Lower Genital Tract Neoplasia Compared With Low-Risk Women. Obstet Gynecol. 2015;126(6):1294-300. 16. Goon P, Morrison V, Fearnhead N, Davies J, Wilson C, Jephcott C, et al. High resolution anoscopy may be useful in achieving reductions in anal cancer local disease failure rates. Eur J Cancer Care (Engl). 2015;24(3):4116. 17. SEER NCI. SEER Stat Fact Sheets: Anal Cancer. 2016; Available from: http://seer.cancer.gov/statfacts/html/anus.html.