Anal Cancer: The Bottom
Line
3 May 2017
Ardis Ann Moe, M.D.
UCLA Center for AIDS Research and Education/NEVHC Van Nuys Adult HIV
Clinic
[email protected]
Case#1
• 60 year old male, MSM/MSW presents to clinic in August 2013.
• AIDS, CD4 count <20 , HIV viral load >100,000 in 2011. Now has 359
CD4 cells and undetectable HIV viral load.
• Hx cryptococcal meningitis and cryptococcal pneumonia
• Hx MAC
• Hx cerebellar stroke from cryptococcal meningitis.
• Last 2 years spent in extensive rehab and now is finally able to drive a
car and he is about to go back to work. Never got rectal exam or
colonoscopy.
• He came in with complaints of anal pain and constipation
• Large, nodular, bloody mass found on rectal exam
• Dead 5 months later from metastatic anal cancer, despite XRT, chemo
and ostomy placement.
Goals:
• Epidemiology of anal cancer
• Pathophysiology of anal cancer and its precursor state
• Current status of screening
• Treatment for anal cancer
• Status of HPV vaccine
• ANCHOR study
Epidemiology of Anal Cancer in
HIV
• In a typical HIV clinic, 1-2 cases a year
• 10% lifetime risk for HIV+ MSM
• 36/100,000 for HIV- MSM (same rate as pre-Pap cervical cancer in
women)
• 1/100,000 for HIV- heterosexual adults.
• Many HIV+ persons with anal cancer have NO history of anal sex.
• Source Modern Colposcopy Textbook and Atlas, 3 ed E.J. Mayeaux M.D. J. Thomas Cox M.D. Chapter 17, page 484-535.
rd
• Median age for anal cancer diagnosis
• 57 in men, and 68 in women
• Source Modern Colposcopy Textbook and Atlas, 3rd ed E.J. Mayeaux M.D. J. Thomas Cox M.D. Chapter 17, page 484-535
Pathophysiology of Anal Cancer
• Risk factors for anal cancer:
• Smoking
• HPV infection, esp with serotypes 16 , or 18
• CD4 count nadir <200
• Untreated HIV
• Females slightly higher risk than males in HIV- population
• Age> 50.
• Source Modern Colposcopy Textbook and Atlas, 3rd ed E.J. Mayeaux M.D. J. Thomas Cox M.D. Chapter 17, page 484-535
• >80% of anal cancer caused by HPV (serotypes 16,18 most common)
• 10% by adenocarcinoma
• HPV causes infection of squamous epithelium, and can cause a type
of cell damage called dysplasia
• The dysplasia is graded as low grade dysplasia (LSIL) , or high grade
dysplasia (HSIL)
• Source Modern Colposcopy Textbook and Atlas, 3rd ed E.J. Mayeaux M.D. J. Thomas Cox M.D. Chapter 17, page 484-535
• >90% of MSM HIV+ have anal HPV
• 59% of MSW HIV+ have anal HPV
• 79% of WSM HIV+ have anal HPV
• HPV in anus common even in persons who have never had anal sex.
• Renal transplant patients have 28% anal HPV
•
Source Modern Colposcopy Textbook and Atlas, 3rd ed E.J. Mayeaux M.D. J. Thomas Cox M.D. Chapter 17, page 484-535
How common is HSIL (severe dysplasia from
HPV)
• MSM with HIV 1/3 to ½ have HSIL on anal exam
• WSM with HIV 9% have HSIL on anal exam
• MSW with HIV 18% have HSIL on anal exam
• Source Modern Colposcopy Textbook and Atlas, 3rd ed E.J. Mayeaux M.D. J. Thomas Cox M.D. Chapter 17, page 484-535
Case #2
• 73 yo male with AIDS came to clinic for routine anal exam.
• CD4 count nadir 53, dx 1983. Now with CD4 count 384 and ND on
HIV viral load
• No symptoms.
• Hemorrhoid tag on external exam to have small whitish nodule .
• + for squamous cell carcinoma.
• Completely excised with clear margins. No chemo or XRT needed.
• In HIV+ , 65% of anal cancers are in the exterior, perianal area
• In HIV- 71-87% are in the anal canal.
• External exam of perianus is as important as the internal exam
• Any unusual tissue on the outside of the anus should be suspect for
anal cancer in HIV+ adults
•
Source Modern Colposcopy Textbook and Atlas, 3rd ed E.J. Mayeaux M.D. J. Thomas Cox M.D. Chapter 17, page 484-535
Case #3
• 25 yo male to female transgender presents to clinic in December
2015 for treatment for AIDS.
• HIV+ at age 15, but never sought treatment
• CD4 count <20, and HIV viral load 140,000
• MAC, Candida esophagitis, wasting syndrome, and painful perianal
ulcers.
• Started HIV meds and overall improved. Weight up 21 lbs and CD4
count now 154 and HIV viral load <20
• Rectal ulcers initially responded to acyclovir, but areas of perianal
ulceration continued
• After many months of treatment with HSV meds, she was referred to
colorectal and the ulcerated areas revealed superficial squamous
carcinoma of the anus.
• This was also completely excised with clear margins.
• Anal and perianal cancer can also present as nonhealing ulcers of the
anal and perianal tissue.
• In addition, chronic anal fistulas can also have internal anal cancers.
• Refer patients with chronic nonhealing anal ulcers and chronic fistulas
to colorectal for evaluation.
Anal fistula
Current Status of Screening
• No clear paradigm for anal cancer prevention on the same level as
cervical cancer
• Most authorities recommend annual rectal exam for HIV+ MSM, and
for HIV+ women with histories of severe cervical dysplasia.
• This recommendation may allow some anal cancers to progress to an
advanced stage before they can be detected.
• Source: Leeds, Ira L. and Fang, Sandy H. Anal Cancer and Intraepithelial Neoplasia Screening: A Review WJGS 2016 January 27;8(1): 41-51
• Anal pap smear controversial:
• Sensitivity for HSIL 69-93% but specificity 32-59%
• Anal pap smear only useful if patients have access to high resolution
anoscopy (HRA)
• HRA expensive: $1300 procedure + $500 for pathology (UCLA)
• Few providers trained in HRA
• Source: E.J. Mayeaux M.D. and J. Thomas Cox, M.D. Modern Colposcopy Textbook and Atlas 3rd ed. Chapter 17: page 484-535
• In a study of 27 HIV+ adults with HSIL that progressed to anal cancer;
23 had anal cancer that could be palpated on rectal exam OR could be
seen on the perianal area as induration or ulceration
• Median 57 months from HSIL to anal cancer
• Source: Berry, J.Michael, et al. Progression of Anal High Grade Squamous Intraepithelia Lesions To Invasive Anal Cancer Among HIV-infected
Men Who have Sex With Men Int. J. Cancer 134, 1147-1155.
Anal Cancer Treatment
• Superficially invasive squamous cell carcinoma (SICCA) T0
• Treated with local incision only; no need for chemo or XRT
• Anal cancers <2 cm, that can be completely excised, have best
prognosis
HPV vaccination
• HPV vaccination, 4- or 9-valent , safe and highly effective in HIV+ boys and girls,
and young men and young women.
• ACTG A5298: No efficacy seen in older HIV+ adults (median age 47 in study).
• In HIV- teens and young men, all MSM, HPV vaccination may decrease rates of
dysplasia
•
Source: E.J. Mayeaux M.D. and J. Thomas Cox, M.D. Modern Colposcopy Textbook and Atlas 3 rd ed. Chapter 17: page 484-535
•
Source: Palefsy, Joel M. et al: NEJM 365: 17 Pages 1576 -1585
•
Source: CROI, Boston, Feb 22-25, 2016. Abstact 161
•
Source: Rainone, V et al. “Human Papilloma Virus Vaccination Induces Strong Human Papilloma Virus Specific Cell Mediated Immune Responses in HIV-infected
Adolescents and Young Adults” AIDS 2015 MEXH 27; 29(6) 739-43.
ANCHOR Study
NIH funded study to develop paradigm for
screening and treatment.
• 5000 adults, all HIV+ and at least 35 years old. 5-7 year study
• 15 sites
• All with HSIL on anal biopsy
• Randomized to every 6 month exams (active monitoring) or
treatment with hyfrecation (preemptive treatment) with followup
exams and additional treatments to eliminate HSIL as needed.
• To demonstrate utility of high resolution anoscopy and possible need
for hyfrecation treatment
Hyfrecation is electrocautery of HSIL lesions.
• Active monitoring arm: repeated HRA exams to find SICCA lesions,
when anal cancer is easily cured with local incision.
• Pre-emptive treatment arm: to burn off HSIL lesions BEFORE they can
become cancer
• “Active monitoring” is like mammogram paradigm.
• “Pre-emptive treatment” is like pap smear paradigm.
Both mammogram paradigm and pap smear/colpo paradigm work to
prevent cancer deaths and morbidity in women.
• Hyfrecation has side effects of causing anal fissures and anal
abscesses and is more expensive than HRA alone.
Conclusions
• Anal cancer is common in HIV+ MSM, and the risk increases with
smoking, CD4 <200 nadir, and age
• HPV is the cause of most anal cancers, and >90% of HIV+ MSM have
HPV
• HPV vaccine helps to prevent HPV disease even in HIV+ young adults,
but not in HIV+ adults> 26 years old. .
• Many anal cancers can be detected with annual rectal exam for
patients who do not have access to HRA
• Hemorrhoids are painful on exam, and feel like small pillows
• Suspicious masses are firm, discolored or whitish. May or may not be painful.
• Any anal mass noted on rectal exam OR any unusual tissue on the
perianal area could be anal cancer. Evaluate with a colorectal surgeon
if any of these abnormalities are present. Its not just “hemorrhoids”
• Pap smear like paradigm for anal cancer prevention yet to be
developed. Tune in for ANCHOR results