Anal Warts and Anal Intradermal Neoplasia

 

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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.

REFERENCES

• 1 McCaffery M. Autopsy of a mummy - warts and all.  Can Fam Physician. 1974;  20 (9) 89-91
  PubMedGoogle Scholar
• 2 Dubash S E. The Zoroastrian sanitary code, with critical and explanatory notes. Bombay: Sanj Vartaman; 1906: 125
  Google Scholar
• 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
  Google Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 5 Straus M, Shaw E. Crystaline virus like particles.  Proc Soc Exp Biol Med. 1949;  72 46-50
  PubMedGoogle Scholar
• 6 zur Hausen H. Condylomata acuminata and human genital cancer.  Cancer Res. 1976;  36 (2 pt 2) 794
  PubMedGoogle Scholar
• 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
  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 Centers for Disease Control .Sexually transmitted diseases surveillance 2008. Atlanta, GA: Centers for Disease Control; 2008
  Google Scholar
• 10 Simms I, Fairley C K. Epidemiology of genital warts in England and Wales: 1971 to 1994.  Genitourin Med. 1997;  73 (5) 365-367
  PubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  PubMedGoogle Scholar
• 13 Fox P A. Human papillomavirus and anal intraepithelial neoplasia.  Curr Opin Infect Dis. 2006;  19 (1) 62-66
  CrossrefPubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  PubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 24 Konya J, Dillner J. Immunity to oncogenic human papillomaviruses.  Adv Cancer Res. 2001;  82 205-238
  PubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  PubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  PubMedGoogle Scholar
• 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
  PubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 38 Reitano M. Counseling patients with genital warts.  Am J Med. 1997;  102 (5A) 38-43
  PubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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]
  Google Scholar
• 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
  PubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  PubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  PubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 49 Metcalf A M, Dean T. Risk of dysplasia in anal condyloma.  Surgery. 1995;  118 (4) 724-726
  CrossrefPubMedGoogle Scholar
• 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
  PubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 52 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
• 53 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
• 54 Goldstone S. A stand against expectant management of anal dysplasia.  Dis Colon Rectum. 2006;  49 (10) 1648-1649, author reply 1649–1650
  CrossrefPubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar

Ignacio EcheniqueM.D. 

Department of Surgery, University of Puerto Rico Medical School

Torre Auxilio Mutuo, Ste. 218, Rio Piedras, PR 00917

Email: iecheniquemd@gmail.com