How might we implement screening for anal cancer in HIV-positive patients?

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Objective How might we implement screening for anal cancer in HIV-positive patients? Identify the elements required to set up an anal cancer screening and prevention program J. Michael Berry, MD Associate Clinical Professor of Medicine University of California San Francisco Associate Director HPV-Related Clinical Studies Email: jmichael.berry@ucsf.edu Disclosures I disclose I received grant research support from Merck & Co (sub-investigator for HPV vaccine studies). Non-FDA-Approved I intend to discuss non-fda-approved use of infrared coagulators for treatment of high-grade anal neoplasia and the use of fluorouracil cream as adjunctive or primary therapy for high-grade anal neoplasia. Why should we consider screening for anal cancer? Anal cancer is a significant and continuing problem for all HIV-positive persons [evidence level B, epidemiological studies] HGAIN is a potentially pre-cancerous lesion [evidence level C, expert opinion] and occurs in more than 50% [evidence level B, clinical cohort studies] Lesions can be identified using HRA [evidence level B, clinical cohort studies] How is prevention of cervical cancer similar to anal cancer? The incidence of cervical cancer has decreased over 70% since screening with cervical cytology or Pap smears began 50 years ago. The anus and cervix are similar tissues and are infected by the same cancer causing types of HPV. Cervical HGN is the precursor to cervical cancer and can be identified and treated using colposcopy. Who should we consider screening for anal cancer? [evidence level b, clinical cohort studies and c, expert opinion] All HIV-positive persons In the absence of having HRA available, anal cytology screening is not recommended Patients at-risk who are not able to be screened should be followed with regular digital rectal exams biannually

How to do an anal Pap smear Determine cytology system used by pathology department Liquid-Based Cytology (LBC) or Conventional Pap (CP): For LBC: cytology collection medium (ThinPrep) and Dacron swab For CP: slide, fixative solution, Dacron swab How to Perform an Anal Pap Smear Insert moistened Dacron swab until it bypasses the internal sphincter and abuts the distal wall of the rectum. Rotate swab in a circular fashion as it is withdrawn in order to sample cells from all aspects of anal canal. Apply enough pressure so that swab bends while slowly removing it. Count slowly to ten before removing swab. Swab should bend slightly with gentle pressure to allow for adequate collection of cells. If the swab is scored, be careful to use firm pressure but not enough to break the swab. Anal Cytology Preserve quickly in liquid medium. Fewer cells exfoliate from the anal canal than the cervix; air-dried artifacts occur more easily on CP. Notify the pathology department to expect anal cytology. How to perform a DRE to screen for anal cancer Insert a gloved and lubricated finger slowly into the rectum Consider using a small amount of lidocaine jelly Apply firm pressure on the external sphincter, allowing it to relax before advancing into the rectum

How to perform a DRE to screen for anal cancer Clinical Signs of Invasive Cancer Once inside the rectum, carefully palpate the entire circumference, beginning in the rectum, feel the mucosa over the internal sphincter and then the walls of the distal anal canal Once completed, examine the prostate Examine the external area by performing a perianal sweep Thickening, induration, or an anorectal mass Extensive perianal lesions with ulceration Ulcerated lesion present with abnormal vessels Focally tender lesions Anal Cancer Detected by DRE Perianal Invasive SCCA Critical elements for an anal cancer screening and prevention program DRE Ability to ablate HGAIN when found Anal cytology What is high-resolution anoscopy? Anus is soaked in 3% acetic acid (vinegar) Examined carefully with a colposcope Most abnormal appearing areas are biopsied Lugol s iodine is used judiciously

Colposcope Parts Video Camera Camera Lens Eye Piece Light Source Objective lens Diopter Scale Demonstration of different types of colposcopes that can be used for HRA Mounting: Swing Arm or Overhead Interpupillary Dial Beam Splitter Magnification Dial Colposcope & digital video imaging system HRA: Essential Equipment Anoscopes (disposable or metal) Forceps: Baby or Mini-baby Tischlers, flexible endoscopic forceps, ENT forceps 3% Acetic Acid, Lugol s & Monsel s solutions K-Y jelly, 1-5% lidocaine gel Non-sterile scopettes, Q-tips, gauze 1% injectable lidocaine, 30 gauge needles, 1 cc syringes Cytology fixative, formalin

Baby Tischler Biopsy Forceps 4 x 2 mm bite HRA: Examination 1) Obtain Pap smear if needed. 2) Lubricate anal canal with K-Y jelly mixed with 1-5% lidocaine gel. 3) Digital Rectal Exam: observe for warts, masses, ulcerations, fissures, focal areas of discomfort or pain with palpation. Palpate prostate gland in men. HRA: Examination 4) Insert anoscope, insert Q-tip wrapped in gauze soaked in 3% acetic acid. Remove anoscope leaving the gauze inside. Soak for 1-2 minutes. 5) Remove gauze and re-insert anoscope. 6) Observe through colposcope slowly withdrawing the anoscope until the SCJ comes into focus. HRA: Examination 7) Examine entire circumference of the SCJ. 8) Thorough exam with biopsies, 10-20 minutes. 9) Re-apply acetic acid liberally during exam. 10) Judicious use of Lugol s iodine. HRA: Examination 11) Manipulate the anoscope and/or use of q-tips to thoroughly view all of the SCJ. 12) Observe the distal anal canal and verge as you withdraw the anoscope. 13) Wipe off lube, apply vinegar to perianal region and examine on lower power.

Hemorrhoid not! HSIL Hemorrhoidal Tags Pre-Acetic Acid Post-Acetic Acid Acetowhite Lesion/HSIL/AIN 2-3 Pre-Acetic Acid Post-Acetic Acid Acetowhite Lesion/HSIL/AIN 2-3

Acetowhite Lesion: AIN 3 Pre-Acetic Acid Post-Acetic Acid High-Grade Vascular Changes: Mosaicism and Punctation High-Grade Vascular Changes: Mosaicism and Punctation Cancers found during HRA Why is HRA important? It s the most effective way of defining and identifying HGAIN Once HGAIN has been confirmed by biopsy, then those lesions can be ablated If you can t see it, you can t treat it Occasionally HRAHRA-directed biopsies identify cancer Atypical vessels Green filter highlighting vascular changes Superficially invasive squamous cell carcinoma

Cancers found during HRA Cancers found during HRA Superficially invasive squamous cell carcinoma Cancers found during HRA Identification of HGAIN using HRA Magnified view highlighting abnormal vessels Diseases of the Colon and Rectum 2009; 52:239-247 Identification of HGAIN using HRA Training in HRA 5 of 34 had HSIL cytology, confirmed by biopsy An additional 10 had HGAIN on biopsy; 2 with negative cytology, 2 with ASCUS and 6 with LSIL 18% with negative cytology, 40% with ASCUS, and 50% with LSIL had HGAIN Didactic courses are conducted by the ASCCP (www.asccp.org) every 1-2 years (next course is in Naples FL December 12-13, 13, 2009) A Basic Colopscopy course is recommended which often can occur simultaneously A preceptorship at an established Anal Neoplasia Clinic is recommended observing HRA exams Performing multiple exams in patients with a high prevalence of lesions is necessary to gain proficiency, which may take 1-5 years

HRA is the cornerstone of an anal cancer screening and prevention program HRA is the best way to detect HGAIN [evidence level B, clinical cohort studies] Many lesions can easily be ablated using infrared coagulation in the office [evidence level B, clinical cohort studies] HRA should guide operative treatment [evidence level C, expert opinion] Surgery is not sufficient to treat HGAIN and must be combined with office-based follow- up and treatment [evidence level B, clinical cohort study] Critical elements for an anal cancer screening and prevention program DRE Ability to ablate HGAIN when found Anal cytology