Anal Cancer and Screening Guidelines for Human Papillomavirus in Men Richard A. Ortoski, DO Christine S. Kell, PhD The association between human papillomavirus (HPV) and anal cancer and the similarities between the “transitional zones” within the cervix and anus have raised questions regarding the medical biology of anal cancer. In recent years, increased rates of HPV infection and anal cancer among men have encouraged the medical community to search for causes and ways to identify the less insidious precursor, anal intraepithelial neoplasia. The “alphabet soup” terminology describing anal cytologic findings obtained by Papanicolaou (Pap) tests and the anal histologic find - ings obtained from biopsy specimens need to be better under - stood as distinct entities. Risk factors for the development of anal cancer have been identified and should be discussed with patients—especially those infected with human immunodefi - ciency virus—who have a much higher than normal risk of anal cancer. The anal Pap test has been used by the Northwest Penn - sylvania Rural AIDS Alliance to detect potential precursors to cancer and degrees of anal dyplasia in patients with HIV infection. The Alliance has been instrumental in creating guidelines for anal Pap testing and encouraging other medical professionals and clinics to do the same, and these guidelines are provided herein. J Am Osteopath Assoc . 2011;111(3 suppl 2):S35-S43 he incidence of anal human papil - demonstrated that anal HPV infection is behavior, external assistant devices, Tlomavirus (HPV) and anal cancer not uncommon in heterosexual men agents to enhance sexual performance, is growing among men, in whom HPV who have not had sex with men. 2 In and numbers of partners—and sexual has been shown to be a major cause, if men with the precursor to anal cancer, partners are affected by each other’s not a necessary cofactor, in the devel - anal intraepithelial neoplasia (AIN), the sexual history. For all of these reasons, opment of anal cancer. 1 Anal intercourse prevalence of HPV infection is high. men who do not identify themselves as is a major risk factor in acquiring HPV This viral infection is the most common homosexual or as men who have sex infection, but at least one study has a sexually transmitted disease in the with men (MSM) may nonetheless be at United States. 3 Persistence of HPV is risk and should be screened and tested associated with clinically identifiable for anal dysplasia and cancer. 2 In MSM lesions and high-grade dysplasia leading and heterosexual men who are immuno - to anogenital cancers, all of which are compromised, including those infected From the departments of family medicine (Dr associated with specific types of HPV. with human immunodeficiency virus Ortoski) and microbiology (Dr Kell) at the Lake In the author’s (R.A.O.) clinical expe - (HIV), the incidence of anal dysplasia Erie College of Osteopathic Medicine in Erie, Penn - 4 sylvania. rience, the patterns of human sexual and cancer is even higher. Patients in Financial Disclosures: The authors have no behavior have been changing—with HIV clinics are offered anal Papanico - conflicts of interest or financial disclosures rele - changes in participant anatomy, risk laou (Pap) tests to screen for cellular vant to the article topic. Address correspondence to Ricahrd A. Ortoski, DO, Professor of Family Medicine, Lake Erie College of Osteopathic Medicine, 1858 W Grandview Blvd, Erie, PA 16509-1025. This supplement is supported by an independent educational grant from Merck & Co, Inc. E-mail: [email protected] Ortoski and Kell • Anal Cancer and Screening Guidelines for HPV in Men JAOA • Supplement 2 • Vol 111 • No 3 • March 2011 • S35 Downloaded From: http://jaoa.org/ by a Lake Erie College of Osteopathic Medicine User on 04/10/2018 changes that may indicate a trend toward medical, and surgical histories are unre - Anatomy Review anal cancer, and perhaps other men at markable for this complaint of rectal Understanding the basic anatomy and risk of anal cancer should also be bleeding. histologic characteristics of the anus and screened. During the physical examination, perianal area is essential in compre - Many clinicians are unfamiliar with the patient’s genitalia are found to be hending the pathologic possibilities of the the procedure and the purpose of anal without mass, discharge, lesions, or evi - region. Figure 1 has been adapted from a Pap testing. Appropriate triage and dence of a hernia, and his perianal area is common sketch found in the literature to referral for care of anal cytologic abnor - pink, warm, dry, and intact. With his illustrate the areas of concern. 5 Just as in malities should ideally be clearly defined permission, the physician performs a dig - cervical Pap test screening, in the anal Pap before implementation of anal Pap test ital rectal examination and palpates a test, the presence of both rectal glandular screening. As more laboratories are nondescript thickened area at the 12- columnar mucosal cells and anal squa - becoming familiar with this test, proce - o’clock position posteriorly and 2 cm into mous mucosal cells (reported simply as dural policies are being written. Industry the anus. No blood is grossly visible on columnar cells and squamous cells) veri - standards have been in the develop - the glove, and the guaiac test result is fies the accuracy of the area needed by mental stages during the timeframe of negative. Other areas of examination are confirming the sampling at the most prox - this article, and early concerns noted by found to be noncontributory. imal area, which is the transition zone, the author (R.A.O.) have inhibited the What are the presumptive diagnoses for f ull interpretation in screening for processing of anal Pap specimens. For in this man? What are the next steps in squamous cell carcinoma (SCC). 3 (Other example, clerical laboratory errors have his diagnostic workup? In the following sources have stated, however, that cyto - occurred because of laboratory workers’ sections, we describe the anatomy of the logic specimens without the presence of unfamiliarity with the test. Cervical anogenital area; highlight characteristics columnar cells should not be rejected cancer screening with cervical cytology is and vaccines for HPV; and provide a solely on this basis. 6) routine, but there is no equivalent widely thorough look at the epidemiology, risk accepted procedure guidelines for men factors, diagnosis, and screening of anal Human Papillomavirus with possible exposure to HPV that can cancer. Case follow-up is provided at the Virologic Characteristics lead to dysplasia, and there are no uni - end of the present article. Human papillomavirus has been found versal guidelines on screening. Available in most types of anal cancers. It is a research, however, identifies HPV as a double-stranded DNA virus that repli - cofactor in the development of anogen - ital cancer. The information presented here will show that screening and testing methods for anal dysplasia are available and need to be communicated. Rectum: Columnar Cell Case Presentation Glandular Mucosa Dentate Line R.S., a 40-year-old man, presented to his Pectinate Line family physician with the chief complaint ͕ Transition Zone of rectal bleeding found on toilet tissue during the past week. He had penile and Anus: Anus: perianal condylomas 15 years ago, but Approximately 4 cm there has been no recurrence that he is Squamous Cell Mucosa aware of. His answers concerning his Anus Verge present illness reveal no history of anal ͕ Anal Margin trauma or penetration, rectal pain or dis - charge, perianal itch, or change in bowel movement habits or appearance. The patient has felt no mass or sores on his genitalia or perianal area and reports no dysuria, frequent urination, or penile dis - Figure 1. The anal canal is approximately 4 cm long from the anal verge (margin) to the transi - tional zone. The dentate line (also called the pectinate line) is located at the proximal end of the charge. He reports using condoms anus. The flat squamous cells of the anal canal end here. The transitional (transition, transformation) during every vaginal and anal penetra - zone has been considered synonymous with the dentate line owing to their proximity, but the tion during his past 2 relationships with transitional zone is actually just proximal to the dentate line, is considered part of the anus, and women, which occurred within the past contains cube-shaped cells called transitional cells. It is the junction between rectal columnar epithe - 2 years. He also has a 23-pack-per-year lium and anal squamous epithelium, similar to the cervical transitional zone. Above the transi - history of smoking tobacco. His family, tional zone is the rectum with its columnar epithelium. Adapted from Netter. 5 S36 • JAOA • Supplement 2 • Vol 111 • No 3 • March 2011 Ortoski and Kell • Anal Cancer and Screening Guidelines for HPV in Men Downloaded From: http://jaoa.org/ by a Lake Erie College of Osteopathic Medicine User on 04/10/2018 cates in the nucleus of squamous epithe - revealed protection against other HPV- malignant melanoma, developing from lial cells, thus its association with cervical, related health concerns, it is conceivable the skin or anal lining. 3 anogenital, and oral areas. Hundreds of that both the quadrivalent and bivalent Not all HPV types have been asso - papillomavirus types are capable of vaccines will be shown to prevent cancers ciated with dyplasia. According to the infecting humans. Most cases of anal of the head and neck, penis, and anus CDC, oncogenic HPV types are believed cancer are linked to infection by HPV-16, due to HPV-16 or HPV-18. 8 The vacci - to be the causative agent in up to 90% of which is closely associated with cervical nation of boys to prevent anogenital and anal cancers.