Anal Warts and Anal Intradermal Neoplasia

ABSTRACT

For the last five millennia we have been dealing with the annoyance of verrucas. Anogenital human papillomavirus (HPV) infection is the most common sexually transmitted disease in the United States and is increasing in incidence. As in other gastrointestinal conditions, HPV infection can lead to a stepwise transition from normal cells to dysplastic cells and then to invasive anal cancer. Knowledge of the natural history of HPV infection, risk factors, diagnostic tools, and therapeutic methods gives us the tools to adequately prevent, evaluate, treat, and counsel our patients. In this review, the authors detail the diagnosis, management, and treatment of anal condyloma and anal intraepithelial neoplasia with a focus on prevention, early detection, and treatment using current data and technology.

KEYWORDS

Anal intraepithelial neoplasia (AIN) - anal condyloma - anal cytology - high-definition anoscopy - human papillomavirus

REFERENCES

• 1 McCaffery M. Autopsy of a mummy - warts and all.  Can Fam Physician. 1974;  20 (9) 89-91
• 2 Dubash S E. The Zoroastrian sanitary code, with critical and explanatory notes. Bombay: Sanj Vartaman; 1906: 125
• 3 Celsus AC. De medicina. Ueber die Artzneiwissenschaft; übersetzt und erklärt von Eduard Scheller: zweite Auflage von Walther Frieboes. Vol. 8. Braunschweig: Vieweg und Sohn; 1906
• 4 Shope R E, Hurst E W. Infectious papillomatosis of rabbits: with a note on the histopathology.  J Exp Med. 1933;  58 (5) 607-624
• 5 Straus M, Shaw E. Crystaline virus like particles.  Proc Soc Exp Biol Med. 1949;  72 46-50
• 6 zur Hausen H. Condylomata acuminata and human genital cancer.  Cancer Res. 1976;  36 (2 pt 2) 794
• 7 Schwarz E, Freese U K, Gissmann L et al.. Structure and transcription of human papillomavirus sequences in cervical carcinoma cells.  Nature. 1985;  314 (6006) 111-114
• 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
• 9 Centers for Disease Control .Sexually transmitted diseases surveillance 2008. Atlanta, GA: Centers for Disease Control; 2008
• 10 Simms I, Fairley C K. Epidemiology of genital warts in England and Wales: 1971 to 1994.  Genitourin Med. 1997;  73 (5) 365-367
• 11 Shvetsov Y B, Hernandez B Y, McDuffie K et al.. Duration and clearance of anal human papillomavirus (HPV) infection among women: the Hawaii HPV cohort study.  Clin Infect Dis. 2009;  48 (5) 536-546
• 12 Law C L, Qassim M, Thompson C H et al.. Factors associated with clinical and sub-clinical anal human papillomavirus infection in homosexual men.  Genitourin Med. 1991;  67 (2) 92-98
• 13 Fox P A. Human papillomavirus and anal intraepithelial neoplasia.  Curr Opin Infect Dis. 2006;  19 (1) 62-66
• 14 Valois R F, Oeltmann J E, Waller J, Hussey J R. Relationship between number of sexual intercourse partners and selected health risk behaviors among public high school adolescents.  J Adolesc Health. 1999;  25 (5) 328-335
• 15 Schelhaas M, Ewers H, Rajamäki M L, Day P M, Schiller J T, Helenius A. Human papillomavirus type 16 entry: retrograde cell surface transport along actin-rich protrusions.  PLoS Pathog. 2008;  4 (9) e1000148
• 16 Schiller J T, Day P M, Kines R C. Current understanding of the mechanism of HPV infection.  Gynecol Oncol. 2010;  118 (1, Suppl) S12-S17
• 17 Kämper N, Day P M, Nowak T et al.. A membrane-destabilizing peptide in capsid protein L2 is required for egress of papillomavirus genomes from endosomes.  J Virol. 2006;  80 (2) 759-768
• 18 Scheurer M E, Tortolero-Luna G, Adler-Storthz K. Human papillomavirus infection: biology, epidemiology, and prevention.  Int J Gynecol Cancer. 2005;  15 (5) 727-746
• 19 Lane D P. Exploiting the p53 pathway for the diagnosis and therapy of human cancer.  Cold Spring Harb Symp Quant Biol. 2005;  70 489-497
• 20 Fenger C, Nielsen V T. Dysplastic changes in the anal canal epithelium in minor surgical specimens.  Acta Pathol Microbiol Scand [A]. 1981;  89 (6) 463-465
• 21 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
• 22 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
• 23 Vernon S D, Holmes K K, Reeves W C. Human papillomavirus infection and associated disease in persons infected with human immunodeficiency virus.  Clin Infect Dis. 1995;  21 (Suppl 1) S121-S124
• 24 Konya J, Dillner J. Immunity to oncogenic human papillomaviruses.  Adv Cancer Res. 2001;  82 205-238
• 25 Nakagawa M, Stites D P, Farhat S et al.. Cytotoxic T lymphocyte responses to E6 and E7 proteins of human papillomavirus type 16: relationship to cervical intraepithelial neoplasia.  J Infect Dis. 1997;  175 (4) 927-931
• 26 Palefsky J M, Holly E A, Hogeboom C J et al.. Virologic, immunologic, and clinical parameters in the incidence and progression of anal squamous intraepithelial lesions in HIV-positive and HIV-negative homosexual men.  J Acquir Immune Defic Syndr Hum Retrovirol. 1998;  17 (4) 314-319
• 27 Hillemanns P, Ellerbrock T V, McPhillips S et al.. Prevalence of anal human papillomavirus infection and anal cytologic abnormalities in HIV-seropositive women.  AIDS. 1996;  10 (14) 1641-1647
• 28 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
• 29 Palefsky J M, Holly E A, Efirdc J T et al.. Anal intraepithelial neoplasia in the highly active antiretroviral therapy era among HIV-positive men who have sex with men.  AIDS. 2005;  19 (13) 1407-1414
• 30 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
• 31 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
• 32 Friedlander M A, Stier E, Lin O. Anorectal cytology as a screening tool for anal squamous lesions: cytologic, anoscopic, and histologic correlation.  Cancer. 2004;  102 (1) 19-26
• 33 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
• 34 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
• 35 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
• 36 Clavel C, Masure M, Bory J P et al.. Human papillomavirus testing in primary screening for the detection of high-grade cervical lesions: a study of 7932 women.  Br J Cancer. 2001;  84 (12) 1616-1623
• 37 Castle P E, Schiffman M, Wheeler C M. Hybrid capture 2 viral load and the 2-year cumulative risk of cervical intraepithelial neoplasia grade 3 or cancer.  Am J Obstet Gynecol. 2004;  191 (5) 1590-1597
• 38 Reitano M. Counseling patients with genital warts.  Am J Med. 1997;  102 (5A) 38-43
• 39 Cleary R K, Schaldenbrand J D, Fowler J J, Schuler J M, Lampman R M. Perianal Bowen's disease and anal intraepithelial neoplasia: review of the literature.  Dis Colon Rectum. 1999;  42 (7) 945-951
• 40 Dindo D, Nocito A, Schettle M, Clavien P A, Hahnloser D. What should we do about anal condyloma and anal intraepithelial neoplasia? Results of a survey.  Colorectal Dis. 2010;  (March) 10 [Epub ahead of print]
• 41 Anderson C A, Boller A M, Richardson C J, Balcos E G, Zera R T. Anal condyloma: a comparison between HIV positive and negative patients.  Am Surg. 2004;  70 (11) 1014-1018
• 42 Klaristenfeld D, Israelit S, Beart R W, Ault G, Kaiser A M. Surgical excision of extensive anal condylomata not associated with risk of anal stenosis.  Int J Colorectal Dis. 2008;  23 (9) 853-856
• 43 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
• 44 Garland S M, Sellors J W, Wikstrom A Imiquimod Study Group et al. Imiquimod 5% cream is a safe and effective self-applied treatment for anogenital warts—results of an open-label, multicentre Phase IIIB trial.  Int J STD AIDS. 2001;  12 (11) 722-729
• 45 Arican O, Guneri F, Bilgic K, Karaoglu A. Topical imiquimod 5% cream in external anogenital warts: a randomized, double-blind, placebo-controlled study.  J Dermatol. 2004;  31 (8) 627-631
• 46 Yan J, Chen S L, Wang H N, Wu T X. Meta-analysis of 5% imiquimod and 0.5% podophyllotoxin in the treatment of condylomata acuminata.  Dermatology. 2006;  213 (3) 218-223
• 47 Schöfer H, Van Ophoven A, Henke U, Lenz T, Eul A. Randomized, comparative trial on the sustained efficacy of topical imiquimod 5% cream versus conventional ablative methods in external anogenital warts.  Eur J Dermatol. 2006;  16 (6) 642-648
• 48 Sobhani I, Vuagnat A, Walker F et al.. Prevalence of high-grade dysplasia and cancer in the anal canal in human papillomavirus-infected individuals.  Gastroenterology. 2001;  120 (4) 857-866
• 49 Metcalf A M, Dean T. Risk of dysplasia in anal condyloma.  Surgery. 1995;  118 (4) 724-726
• 50 Frazer I H, Medley G, Crapper R M, Brown T C, Mackay I R. Association between anorectal dysplasia, human papillomavirus, and human immunodeficiency virus infection in homosexual men.  Lancet. 1986;  2 (8508) 657-660
• 51 Chang G J, Berry J M, Jay N, Palefsky J M, Welton M L. Surgical treatment of high-grade anal squamous intraepithelial lesions: a prospective study.  Dis Colon Rectum. 2002;  45 (4) 453-458
• 52 Devaraj B, Cosman B C. Expectant management of anal squamous dysplasia in patients with HIV.  Dis Colon Rectum. 2006;  49 (1) 36-40
• 53 Sobhani I, Walker F, Roudot-Thoraval F et al.. Anal carcinoma: incidence and effect of cumulative infections.  AIDS. 2004;  18 (11) 1561-1569
• 54 Goldstone S. A stand against expectant management of anal dysplasia.  Dis Colon Rectum. 2006;  49 (10) 1648-1649, author reply 1649–1650
• 55 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
• 56 Mahto M, Nathan M, O'Mahony C. More than a decade on: review of the use of imiquimod in lower anogenital intraepithelial neoplasia.  Int J STD AIDS. 2010;  21 (1) 8-16
• 57 de la Fuente S G, Ludwig K A, Mantyh C R. Preoperative immune status determines anal condyloma recurrence after surgical excision.  Dis Colon Rectum. 2003;  46 (3) 367-373
• 58 Palefsky J M, Holly E A, Ralston M L, Jay N, Berry J M, Darragh T M. High incidence of anal high-grade squamous intra-epithelial lesions among HIV-positive and HIV-negative homosexual and bisexual men.  AIDS. 1998;  12 (5) 495-503
• 59 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
• 60 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