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Clin Colon Rectal Surg 2009; 22(2): 094-101
DOI: 10.1055/s-0029-1223840
© Thieme Medical Publishers

Management of Anal Squamous Intraepithelial Lesions

Carlos E. Pineda1 , Mark L. Welton1
  • 1Section of Colon and Rectal Surgery, Stanford University School of Medicine, Stanford, California
Further Information

Publication History

Publication Date:
27 May 2009 (online)

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ABSTRACT

Anal squamous intraepithelial lesions include both low-grade squamous intraepithelial lesions (LSIL) and high-grade squamous intraepithelial lesions (HSIL) and are caused by chronic infection with the human papillomavirus (HPV). The disease is increasing in both incidence and prevalence, especially among patients with the following risk factors: homosexual men, acquired or iatrogenic immunosuppression, and presence of other HPV-related diseases. Although the natural history of the disease is unknown, there is significant evidence that untreated HSIL progresses to squamous cell carcinoma in 11% of patients and in up to 50% of patients with extensive disease and immunosuppression. Anal cytology and reflex HPV DNA testing are used to screen for disease, particularly among patients with the aforementioned risk factors. Evaluation of the patient should include physical examination and high-resolution anoscopy (HRA) to evaluate for disease above and below the dentate line. Intervention is warranted and this can be achieved in many ways. The treatment option associated with the best outcomes is ablation directed with HRA, which can be performed in the office or in the operating room with minimal morbidity. This strategy is effective in patients with both low-volume and high-volume disease and is associated with a malignant progression rate of 0.4% in patients with treated HSIL.

KEYWORDS

Anal squamous dysplasia - high-grade squamous intraepithelial lesions - high-resolution anoscopy

REFERENCES

  • 1 Pineda C E, Welton M L. Controversies in the management of anal high-grade squamous intraepithelial lesions.  Minerva Chir. 2008;  63(5) 389-399
    PubMedGoogle Scholar
  • 2 Apgar B S, Zoschnick L, Wright Jr T C. The 2001 Bethesda System terminology.  Am Fam Physician. 2003;  68(10) 1992-1998
    PubMedGoogle Scholar
  • 3 Longacre T A, Kong C S, Welton M L. Diagnostic problems in anal pathology.  Adv Anat Pathol. 2008;  15(5) 263-278
    CrossrefPubMedGoogle Scholar
  • 4 Grodsky L. Bowen's disease of the anal region: squamous cell carcinoma in situ; report of three cases.  Am J Surg. 1954;  88(5) 710-714
    CrossrefPubMedGoogle Scholar
  • 5 Welton M L, Amerhauser A, Litle V R, Leavenworth J D, Darragh T M, Palefsky J M. Anal Bowen's disease and high-grade squamous intraepithelial lesions are histologically and immunohistochemically indistinguishable.  , [meeting abstract] Dis Colon Rectum. 2001;  44 A32
    PubMedGoogle Scholar
  • 6 Fleshner P R, Chalasani S, Chang G J, Levien D H, Hyman N H, Buie W D. Standards Practice Task Force, American Society of Colon and Rectal Surgeons . Practice parameters for anal squamous neoplasms.  Dis Colon Rectum. 2008;  51(1) 2-9
    CrossrefPubMedGoogle Scholar
  • 6a Edge S B. AJCC Cancer Staging Manual. 7th edition.  , In press
    PubMedGoogle Scholar
  • 7 Varnai A D, Bollmann M, Griefingholt H et al.. HPV in anal squamous cell carcinoma and anal intraepithelial neoplasia (AIN). Impact of HPV analysis of anal lesions on diagnosis and prognosis.  Int J Colorectal Dis. 2006;  21(2) 135-142
    CrossrefPubMedGoogle Scholar
  • 8 Welton M L, Sharkey F E, Kahlenberg M S. The etiology and epidemiology of anal cancer.  Surg Oncol Clin N Am. 2004;  13(2) 263-275
    CrossrefPubMedGoogle Scholar
  • 9 Litle V R, Leavenworth J D, Darragh T M et al.. Angiogenesis, proliferation, and apoptosis in anal high-grade squamous intraepithelial lesions.  Dis Colon Rectum. 2000;  43(3) 346-352
    PubMedGoogle Scholar
  • 10 D'Souza G, Wiley D J, Li X et al.. Incidence and epidemiology of anal cancer in the multicenter AIDS cohort study.  J Acquir Immune Defic Syndr. 2008;  48(4) 491-499
    PubMedGoogle Scholar
  • 11 Adami J, Gäbel H, Lindelöf B et al.. Cancer risk following organ transplantation: a nationwide cohort study in Sweden.  Br J Cancer. 2003;  89(7) 1221-1227
    CrossrefPubMedGoogle Scholar
  • 12 Stier E A, Krown S E, Chi D S, Brown C L, Chiao E Y, Lin O. Anal dysplasia in HIV-infected women with cervical and vulvar dysplasia.  J Low Genit Tract Dis. 2004;  8(4) 272-275
    CrossrefPubMedGoogle Scholar
  • 13 Frisch M. On the etiology of anal squamous carcinoma.  Dan Med Bull. 2002;  49(3) 194-209
    PubMedGoogle Scholar
  • 14 Abramowitz L, Benabderrahmane D, Ravaud P et al.. Anal squamous intraepithelial lesions and condyloma in HIV-infected heterosexual men, homosexual men and women: prevalence and associated factors.  AIDS. 2007;  21(11) 1457-1465
    CrossrefPubMedGoogle Scholar
  • 15 Sobhani I, Walker F, Roudot-Thoraval F et al.. Anal carcinoma: incidence and effect of cumulative infections.  AIDS. 2004;  18(11) 1561-1569
    CrossrefPubMedGoogle Scholar
  • 16 Gohy L, Gorska I, Rouleau D HIPVIRG Study Group et al. Genotyping of human papillomavirus DNA in anal biopsies and anal swabs collected from HIV-seropositive men with anal dysplasia.  J Acquir Immune Defic Syndr. 2008;  49(1) 32-39
    CrossrefPubMedGoogle Scholar
  • 17 Johnson L G, Madeleine M M, Newcomer L M, Schwartz S M, Daling J R. Anal cancer incidence and survival: the surveillance, epidemiology, and end results experience, 1973-2000.  Cancer. 2004;  101(2) 281-288
    CrossrefPubMedGoogle Scholar
  • 18 Cress R D, Holly E A. Incidence of anal cancer in California: increased incidence among men in San Francisco, 1973-1999.  Prev Med. 2003;  36(5) 555-560
    CrossrefPubMedGoogle Scholar
  • 19 Koblin B A, Hessol N A, Zauber A G et al.. Increased incidence of cancer among homosexual men, New York City and San Francisco, 1978-1990.  Am J Epidemiol. 1996;  144(10) 916-923
    PubMedGoogle Scholar
  • 20 Frisch M, Melbye M, Møller H. Trends in incidence of anal cancer in Denmark.  BMJ. 1993;  306(6875) 419-422
    PubMedGoogle Scholar
  • 21 Ciobotaru B, Leiman G, St John T, Hyman N, Ramundo M, Grace C. Prevalence and risk factors for anal cytologic abnormalities and human papillomavirus infection in a rural population of HIV-infected males.  Dis Colon Rectum. 2007;  50(7) 1011-1016
    CrossrefPubMedGoogle Scholar
  • 22 Marfing T E, Abel M E, Gallagher D M. Perianal Bowen's disease and associated malignancies. Results of a survey.  Dis Colon Rectum. 1987;  30(10) 782-785
    PubMedGoogle Scholar
  • 23 Devaraj B, Cosman B C. Expectant management of anal squamous dysplasia in patients with HIV.  Dis Colon Rectum. 2006;  49(1) 36-40
    CrossrefPubMedGoogle Scholar
  • 24 Scholefield J H, Castle M T, Watson N F. Malignant transformation of high-grade anal intraepithelial neoplasia.  Br J Surg. 2005;  92(9) 1133-1136
    CrossrefPubMedGoogle Scholar
  • 25 Herat A, Shirato K, Damian D L, Finlayson R, Whitfeld M. Invasive squamous cell carcinoma arising in refractory perianal Bowen's disease in a HIV-positive individual.  Australas J Dermatol. 2006;  47(2) 120-123
    CrossrefPubMedGoogle Scholar
  • 26 Pineda C E, Berry J M, Jay N, Palefsky J M, Welton M L. High resolution anoscopy in the planned staged treatment of anal squamous intraepithelial lesions in HIV-negative patients.  J Gastrointest Surg. 2007;  11(11) 1410-1415 discussion 1415-1416 discussion 5-6
    CrossrefPubMedGoogle Scholar
  • 27 Kreuter A, Brockmeyer N H, Hochdorfer B et al.. Clinical spectrum and virologic characteristics of anal intraepithelial neoplasia in HIV infection.  J Am Acad Dermatol. 2005;  52(4) 603-608
    CrossrefPubMedGoogle Scholar
  • 28 Watson A J, Smith B B, Whitehead M R, Sykes P H, Frizelle F A. Malignant progression of anal intra-epithelial neoplasia.  ANZ J Surg. 2006;  76(8) 715-717
    CrossrefPubMedGoogle Scholar
  • 29 Jay N, Berry J M, Hogeboom C J, Holly E A, Darragh T M, Palefsky J M. Colposcopic appearance of anal squamous intraepithelial lesions: relationship to histopathology.  Dis Colon Rectum. 1997;  40(8) 919-928
    CrossrefPubMedGoogle Scholar
  • 30 O'Connor J J. The study of anorectal disease by colposcopy.  Dis Colon Rectum. 1977;  20(7) 570-572
    CrossrefPubMedGoogle Scholar
  • 31 Pineda C E, Berry J M, Welton M L. High resolution anoscopy and targeted treatment of high-grade squamous intraepithelial lesions.  Dis Colon Rectum. 2006;  49(1) 126
    CrossrefPubMedGoogle Scholar
  • 32 Tramujas da Costa e Silva I, de Lima Ferreira L C, Santos Gimenez F et al.. High-resolution anoscopy in the diagnosis of anal cancer precursor lesions in renal graft recipients.  Ann Surg Oncol. 2008;  15(5) 1470-1475
    CrossrefPubMedGoogle Scholar
  • 33 Chung A P, Rosenfeld D B. Intraoperative high-resolution anoscopy: a minimally invasive approach in the treatment of patients with Bowen's disease and results in a private practice setting.  Am Surg. 2007;  73(12) 1279-1283
    PubMedGoogle Scholar
  • 34 Cranston R D, Darragh T M, Holly E A et al.. Self-collected versus clinician-collected anal cytology specimens to diagnose anal intraepithelial neoplasia in HIV-positive men.  J Acquir Immune Defic Syndr. 2004;  36(4) 915-920
    CrossrefPubMedGoogle Scholar
  • 35 Chin-Hong P V, Berry J M, Cheng S C et al.. Comparison of patient- and clinician-collected anal cytology samples to screen for human papillomavirus-associated anal intraepithelial neoplasia in men who have sex with men.  Ann Intern Med. 2008;  149(5) 300-306
    CrossrefPubMedGoogle Scholar
  • 36 Solomon D, Davey D, Kurman R Forum Group Members et al. The 2001 Bethesda System: terminology for reporting results of cervical cytology.  JAMA. 2002;  287(16) 2114-2119
    CrossrefPubMedGoogle Scholar
  • 37 Palefsky J M, Holly E A, Hogeboom C J, Berry J M, Jay N, Darragh T M. Anal cytology as a screening tool for anal squamous intraepithelial lesions.  J Acquir Immune Defic Syndr Hum Retrovirol. 1997;  14(5) 415-422
    CrossrefPubMedGoogle Scholar
  • 38 de Ruiter A, Carter P, Katz D R et al.. A comparison between cytology and histology to detect anal intraepithelial neoplasia.  Genitourin Med. 1994;  70(1) 22-25
    PubMedGoogle Scholar
  • 39 Panther L A, Wagner K, Proper J et al.. High resolution anoscopy findings for men who have sex with men: inaccuracy of anal cytology as a predictor of histologic high-grade anal intraepithelial neoplasia and the impact of HIV serostatus.  Clin Infect Dis. 2004;  38(10) 1490-1492
    CrossrefPubMedGoogle Scholar
  • 40 Arain S, Walts A E, Thomas P, Bose S. The anal Pap smear: cytomorphology of squamous intraepithelial lesions.  Cytojournal. 2005;  2(1) 4
    CrossrefPubMedGoogle Scholar
  • 41 Fox P A, Seet J E, Stebbing J et al.. The value of anal cytology and human papillomavirus typing in the detection of anal intraepithelial neoplasia: a review of cases from an anoscopy clinic.  Sex Transm Infect. 2005;  81(2) 142-146
    CrossrefPubMedGoogle Scholar
  • 42 Nadal S R, Calore E E, Nadal L R, Horta S H, Manzione C R. [Anal cytology for screening of pre-neoplasic lesions].  Rev Assoc Med Bras. 2007;  53(2) 147-151
    PubMedGoogle Scholar
  • 43 Garcia F U, Haber M M, Butcher J, Sharma M, Nagle D. Increased sensitivity of anal cytology in evaluation of internal compared with external lesions.  Acta Cytol. 2007;  51(6) 893-899
    PubMedGoogle Scholar
  • 44 Cranston R D, Hart S D, Gornbein J A, Hirschowitz S L, Cortina G, Moe A A. The prevalence, and predictive value, of abnormal anal cytology to diagnose anal dysplasia in a population of HIV-positive men who have sex with men.  Int J STD AIDS. 2007;  18(2) 77-80
    CrossrefPubMedGoogle Scholar
  • 45 Mathews W C, Sitapati A, Caperna J C, Barber R E, Tugend A, Go U. Measurement characteristics of anal cytology, histopathology, and high-resolution anoscopic visual impression in an anal dysplasia screening program.  J Acquir Immune Defic Syndr. 2004;  37(5) 1610-1615
    CrossrefPubMedGoogle Scholar
  • 46 Lytwyn A, Salit I E, Raboud J et al.. Interobserver agreement in the interpretation of anal intraepithelial neoplasia.  Cancer. 2005;  103(7) 1447-1456
    CrossrefPubMedGoogle Scholar
  • 47 Scott H, Khoury J, Moore B A, Weissman S. Routine anal cytology screening for anal squamous intraepithelial lesions in an urban HIV clinic.  Sex Transm Dis. 2008;  35(2) 197-202
    PubMedGoogle Scholar
  • 48 Wright Jr T C, Massad L S, Dunton C J, Spitzer M, Wilkinson E J, Solomon D. 2006 ASCCP-Sponsored Consensus Conference . 2006 consensus guidelines for the management of women with abnormal cervical screening tests.  J Low Genit Tract Dis. 2007;  11(4) 201-222
    CrossrefPubMedGoogle Scholar
  • 49 Goldstone S E, Kawalek A Z, Goldstone R N, Goldstone A B. Hybrid Capture II detection of oncogenic human papillomavirus: a useful tool when evaluating men who have sex with men with atypical squamous cells of undetermined significance on anal cytology.  Dis Colon Rectum. 2008;  51(7) 1130-1136
    CrossrefPubMedGoogle Scholar
  • 50 Walts A E, Thomas P, Bose S. Anal cytology: is there a role for reflex HPV DNA testing?.  Diagn Cytopathol. 2005;  33(3) 152-156
    CrossrefPubMedGoogle Scholar
  • 51 Papaconstantinou H T, Lee A J, Simmang C L et al.. Screening methods for high-grade dysplasia in patients with anal condyloma.  J Surg Res. 2005;  127(1) 8-13
    CrossrefPubMedGoogle Scholar
  • 52 Goldie S J, Kuntz K M, Weinstein M C, Freedberg K A, Welton M L, Palefsky J M. The clinical effectiveness and cost-effectiveness of screening for anal squamous intraepithelial lesions in homosexual and bisexual HIV-positive men.  JAMA. 1999;  281(19) 1822-1829
    CrossrefPubMedGoogle Scholar
  • 53 Goldie S J, Kuntz K M, Weinstein M C, Freedberg K A, Palefsky J M. Cost-effectiveness of screening for anal squamous intraepithelial lesions and anal cancer in human immunodeficiency virus-negative homosexual and bisexual men.  Am J Med. 2000;  108(8) 634-641
    CrossrefPubMedGoogle Scholar
  • 54 van Poelgeest M I, van Seters M, van Beurden M et al.. Detection of human papillomavirus (HPV) 16-specific CD4+ T-cell immunity in patients with persistent HPV16-induced vulvar intraepithelial neoplasia in relation to clinical impact of imiquimod treatment.  Clin Cancer Res. 2005;  11(14) 5273-5280
    CrossrefPubMedGoogle Scholar
  • 55 Wieland U, Brockmeyer N H, Weissenborn S J et al.. Imiquimod treatment of anal intraepithelial neoplasia in HIV-positive men.  Arch Dermatol. 2006;  142(11) 1438-1444
    CrossrefPubMedGoogle Scholar
  • 56 Kreuter A, Potthoff A, Brockmeyer N H German Competence Network HIV/AIDS et al. Imiquimod leads to a decrease of human papillomavirus DNA and to a sustained clearance of anal intraepithelial neoplasia in HIV-infected men.  J Invest Dermatol. 2008;  128(8) 2078-2083
    CrossrefPubMedGoogle Scholar
  • 57 Sanclemente G, Herrera S, Tyring S K et al.. Human papillomavirus (HPV) viral load and HPV type in the clinical outcome of HIV-positive patients treated with imiquimod for anogenital warts and anal intraepithelial neoplasia.  J Eur Acad Dermatol Venereol. 2007;  21(8) 1054-1060
    CrossrefPubMedGoogle Scholar
  • 58 Palefsky J M, Berry J M, Jay N et al.. A trial of SGN-00101 (HspE7) to treat high-grade anal intraepithelial neoplasia in HIV-positive individuals.  AIDS. 2006;  20(8) 1151-1155
    PubMedGoogle Scholar
  • 59 Einstein M H, Kadish A S, Burk R D et al.. Heat shock fusion protein-based immunotherapy for treatment of cervical intraepithelial neoplasia III.  Gynecol Oncol. 2007;  106(3) 453-460
    CrossrefPubMedGoogle Scholar
  • 60 Webber J, Fromm D. Photodynamic therapy for carcinoma in situ of the anus.  Arch Surg. 2004;  139(3) 259-261
    PubMedGoogle Scholar
  • 61 Strauss R J, Fazio V W. Bowen's disease of the anal and perianal area. A report and analysis of twelve cases.  Am J Surg. 1979;  137(2) 231-234
    CrossrefPubMedGoogle Scholar
  • 62 Marchesa P, Fazio V W, Oliart S, Goldblum J R, Lavery I C. Perianal Bowen's disease: a clinicopathologic study of 47 patients.  Dis Colon Rectum. 1997;  40(11) 1286-1293
    CrossrefPubMedGoogle Scholar
  • 63 Beck D E, Fazio V W, Jagelman D G, Lavery I C. Perianal Bowen's disease.  Dis Colon Rectum. 1988;  31(6) 419-422
    PubMedGoogle Scholar
  • 64 Margenthaler J A, Dietz D W, Mutch M G, Birnbaum E H, Kodner I J, Fleshman J W. Outcomes, risk of other malignancies, and need for formal mapping procedures in patients with perianal Bowen's disease.  Dis Colon Rectum. 2004;  47(10) 1655-1660 discussion 1660-1661 discussion 60-1
    CrossrefPubMedGoogle Scholar
  • 65 Brown S R, Skinner P, Tidy J, Smith J H, Sharp F, Hosie K B. Outcome after surgical resection for high-grade anal intraepithelial neoplasia (Bowen's disease).  Br J Surg. 1999;  86(8) 1063-1066
    CrossrefPubMedGoogle Scholar
  • 66 Colquhoun P, Nogueras J J, Dipasquale B, Petras R, Wexner S D, Woodhouse S. Interobserver and intraobserver bias exists in the interpretation of anal dysplasia.  Dis Colon Rectum. 2003;  46(10) 1332-1336 discussion 1336-1338 discussion 6-8
    CrossrefPubMedGoogle Scholar
  • 67 Goldstone S E, Kawalek A Z, Huyett J W. Infrared coagulator: a useful tool for treating anal squamous intraepithelial lesions.  Dis Colon Rectum. 2005;  48(5) 1042-1054
    CrossrefPubMedGoogle Scholar
  • 68 Goldstone S E, Hundert J S, Huyett J W. Infrared coagulator ablation of high-grade anal squamous intraepithelial lesions in HIV-negative males who have sex with males.  Dis Colon Rectum. 2007;  50(5) 565-575
    CrossrefPubMedGoogle Scholar
  • 69 Cranston R D, Hirschowitz S L, Cortina G, Moe A A. A retrospective clinical study of the treatment of high-grade anal dysplasia by infrared coagulation in a population of HIV-positive men who have sex with men.  Int J Std AIDS. 2008;  19(2) 118-120
    CrossrefPubMedGoogle Scholar
  • 70 Pineda C E, Berry J M, Jay N, Palefsky J M, Welton M L. High-resolution anoscopy targeted surgical destruction of anal high-grade squamous intraepithelial lesions: a ten-year experience.  Dis Colon Rectum. 2008;  51(6) 829-835 discussion 835-837 discussion 35-7
    CrossrefPubMedGoogle Scholar
  • 71 Nathan M, Hickey N, Mayuranathan L, Vowler S L, Singh N. Treatment of anal human papillomavirus-associated disease: a long term outcome study.  Int J Std AIDS. 2008;  19(7) 445-449
    CrossrefPubMedGoogle Scholar

Carlos E PinedaM.D. 

Section of Colon and Rectal Surgery, Stanford University School of Medicine

300 Pasteur Dr., Stanford, CA 94305

Email: cepineda@stanford.edu

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