Anal Cancer: The Bottom Line

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Anal Cancer: The Bottom Line




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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

amoe@mednet.ucla.edu

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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.

Slide4

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.

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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

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Epidemiology of Anal Cancer in HIV

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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

rd

ed

E.J.

Mayeaux

M.D. J. Thomas Cox M.D. Chapter 17, page 484-535

.

Slide10

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Median age for anal cancer diagnosis

57 in men, and 68 in women

Source Modern Colposcopy Textbook and Atlas, 3

rd

ed

E.J.

Mayeaux

M.D. J. Thomas Cox M.D. Chapter 17, page 484-535

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Pathophysiology of Anal Cancer

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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, 3

rd

ed

E.J.

Mayeaux

M.D. J. Thomas Cox M.D. Chapter 17, page 484-535

Slide15

>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, 3

rd

ed

E.J.

Mayeaux

M.D. J. Thomas Cox M.D. Chapter 17, page 484-535

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Slide17

>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, 3

rd

ed

E.J.

Mayeaux

M.D. J. Thomas Cox M.D. Chapter 17, page 484-535

Slide18

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, 3

rd

ed

E.J.

Mayeaux

M.D. J. Thomas Cox M.D. Chapter 17, page 484-535

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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.

Slide24

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, 3

rd

ed

E.J.

Mayeaux

M.D. J. Thomas Cox M.D. Chapter 17, page 484-535

Slide25

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.

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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

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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.

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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.

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Anal fistula

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Current Status of Screening

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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

Slide35

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 3

rd

ed. Chapter 17: page 484-535

Slide36

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.

Slide37

Anal Cancer Treatment

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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

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HPV vaccination

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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.

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ANCHOR Study

Slide47

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

Slide48

Hyfrecation

is electrocautery of HSIL lesions.

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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

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“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.

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Conclusions

Slide54

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. .

Slide55

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

Slide56


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