Anal Cytology

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Anal Cytology

• Jeffrey Beal, M.D.
• Clinical Director, Florida/Caribbean AIDS
  Education and Training Center

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Anal Cytology Learning Objective

• Discuss the recommended frequency and specimen
  collection technique, and cite indications for
  high resolution anoscopy, biopsy, for anal
  cytology smears in HIV men and women.

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Anal Cancer

• Uncommon in the general population
• Current rate 0.9 cases per 100,000 persons
• MSM incidence 25-37 per 100,000
• HIV MSM 100 per 100,000
• Ball, C. AIDS Reader. 2004 14478-481

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Anal Cancer

• The incidence of anal cancer is also elevated
  among HIV-positive women compared to the general
  population.
• Frisch M, et.al, Human papillomavirus-associated
  cancers in patients with human immunodeficiency
  virus infection and acquired immunodeficiency
  syndrome. J Natl Cancer Inst. 2000 921500-1510

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Anal Cancer as a STD

• Like cervical cancer, linked to HPV
• HPV in anogenital region can present
• Asymptomatic
• Flat barely discernible patches
• Bulky bleeding masses
• Why some become oncogenic is unknown

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Anal Intraepithelial Neoplasia

• Left untreated, anal cancer is fatal. If
  detected at an early stage, however, survival is
  excellent among both HIV and HIV MSM. Like
  cervical cancer, anal cancer is probably
  preventable.
• Screening for and Treatment of Anal
  Intraepithelial Neoplasia Joel Palefsky, MD
  HIV/AIDS Update 2002 MEDSCAPE 2002

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Treatment of Anal Cancer

• The best way to treat invasive anal cancer is to
  prevent it in the first place.
• Panther, et. al. Spectrum of Human
  Papillomavirus-Related Dysplasia and Carcinoma of
  the Anus in HIV-infected Patients February 2005
  The AIDS Reader, Vol 15, No. 2.

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Anal Cytology

• Anal cytology sensitivity appears similar to
  cervical Pap smears, although the grade of
  dysplasia may not correlate as well with the
  histology

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Anal Cytology

• Cost/Benefit Analysis
• Screening q 2 years beginning during acute HIV
  infection hypothetical cohort HIV MSM
• Cost of 13,000 per quality-adjusted life year
• Annual screening augmented this benefit at a cost
  of 16,000 per QALY saved
• TMP-SMX for PCP prophylaxis results in cost of
  13,000 per year of life saved.
• Goldie, et.al. May 19, 1999 JAMA

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Anal Cytology, Who to screen?

• MSM
• HIV-positive individuals
• History of receptive anal intercourse
• Women with a history of high-grade CIN/cervical
  cancer or vulvar intraepithelial neoplasia/vulvar
  cancer
• Men and Women w/h/o perianal condlyoma
• Screening for and Treatment of Anal
  Intraepithelial Neoplasia Joel Palefsky, MD
  HIV/AIDS Update 2002 MEDSCAPE 2002
• Panther, et. al. Spectrum of Human
  Papillomavirus-Related Dysplasia and Carcinoma of
  the Anus in HIV-infected Patients February 2005
  The AIDS Reader, Vol 15, No. 2.

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Anal Cytology Guidelines

• No universally accepted guidelines
• Not yet considered Standard of Care
• Recommendations
• Perform initial exam and if normal assess risk
  yearly
• HIV MSM yearly consider more frequent when CD4
  lt 200 cells/mm3
• Abnormal results refer for high-resolution a

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Case

• 51 year old white male
• MSM, known HIV positive for 6 years
• Anal receptive
• Past history of anal condyloma excised
• CD4 over 1000 on Sustiva/Combivir VL lt 50
  copies/mL

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Case- page 2

• Normal H P except anal ulceration- fissure
• Asymptomatic except for occasional episodes of
  bleeding
• Prior physician exams x 2 resulted in conclusion
  that this was a fissure with recommendations to
  soften stool and avoid anal sex. No follow-up
  evaluation recommended
• No anal pap ever performed or discussed

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Anal Cytology Procedure

• Procedure
• Moistened Dacron swab inserted 1-1.5 into anal
  canal
• Rotate swab and withdraw in a tight spiral
  motion. Sampling process of 15-20 seconds.
• Smear on glass slide and fix immediately or use
  Thin Prep liquid based media

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Case- Page 3

• Initial anal pap
• ANAL, MISCELLANEOUS SMEAR CYTOLOGY
• Diagnosis INCONCLUSIVE.
• SQUAMOUS DYSPLASIA ASSOCIATED WITH HPV CHANGES,
  CANNOT RULE OUT A MORE SERIOUS PROCESS.

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Case- Page 4

• Patient returns to the office with Pap of
  ulceration
• Result
• AT LEAST MILD SQUAMOUS DYSPLASIA SEEN.
• HIGH GRADE SQUAMOUS LESION CANNOT BE EXCLUDED.

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Anal Cytology Algorithm
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Anal Dysplasia Treatment Options

• Surgical Excision (laser, electrocautery or
  cold-knife)
• Cryotherapy
• Laser therapy
• Infrared photocoagulation
• Bichloroacetic acid/trichloroacetic acid
• Podophyllotoxin
• Interferon
• F-fluorouracil (5-FU)
• Imiquimod (Aldara)
• cidofovir

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Case- Page 5

• Referral to Colorectal surgeon
• Excision of lesion revealed invasive squamous
  cell carcinoma of the rectum with adequate deep
  margin but inadequate lateral margins
• Patient underwent repeat excision with free
  margins
• Follow-up
• 6 month, then yearly anal cytology

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Case Page 6

• 6 month and 1year follow-up cytology negative

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Anal Intraepithelial Neoplasia

• Treatment of AIN has not been shown to prevent
  anal cancer. This is a serious impediment.
  Unfortunately, it becomes a self-fulfilling
  prophecy we will not know until we try it.
  Cervical cytology screening was practiced for
  many years before it became clear that it was
  contributing to the reduction in cervical cancer
  incidence.
• Screening for and Treatment of Anal
  Intraepithelial Neoplasia Joel Palefsky, MD
  HIV/AIDS Update 2002 MEDSCAPE 2002

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Anal HPV Infection Symptoms

• Asymptomatic
• Occasionally patient report
• Itching
• Bleeding
• Pain with defecation
• Receptive anal dyspareunia
• Panther, et. al. Spectrum of Human
  Papillomavirus-Related Dysplasia and Carcinoma of
  the Anus in HIV-infected Patients February 2005
  The AIDS Reader, Vol 15, No. 2.

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Symptoms of Anal Cancer

• Anal pain
• Bleeding
• Growing anal mass
• Discomfort with defecation
• Discomfort with anal intercourse
• Panther, et. al. Spectrum of Human
  Papillomavirus-Related Dysplasia and Carcinoma of
  the Anus in HIV-infected Patients February 2005
  The AIDS Reader, Vol 15, No. 2.

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Prevalence of Anal Cytology Abnormalities in HIV
Patients

• High in HIV women
• High in MSM
• High in HIV heterosexual IVDU (lower than MSM)
• Little is known about the rate in non-IVDU
  heterosexual men.

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Anal Culposcopy

• Soak a gauze 4x4 in 3 acetic acid and wrap
  around the handle of a 1-tip or scopette
• Insert anoscope
• Insert the acetic acid soaked gauze and remove
  the anoscope leaving the gauze
• Allow the vinegar soln. to saturate the
  epithelium 2-3 minutes.
• Remove the swab,
• Reinsert the anoscope
• Use culposcope for microscopic visualization
• Davey, M.D. Diagnostic Cytopathology, Vol. 30,
  No. 6

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High Resolution Anoscopy1

• Insert a clear plastic anoscope and using a
  standard gynecologic colposcope and 3 acetic
  acid solution applied to the anal mucosa, locate
  the transformation zone
• Dysplasia opaque white (acetowhite)
• High-grade dysplasia exists if hallmark surface
  vessel changes consistent with neovascularization
  are visible within the plaque under high-power
  (x20) magnification

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High Resolution Anoscopy2

• Application of Lugol iodine solution
• Cells with high nucleus-cytoplasm ratios
  comprising dysplasia do not absorb Lugol and
  appear bright yellow
• Cells of normal epithelium with relatively more
  cytoplasm take up the iodine and appear dark
  brown
• Last, anoscopic exam of the perianal area is
  performed using 3 acetic acid