Should Anal Pap Smears Be a Standard of Care in HIV Management?

Should Anal Pap Smears Be a Standard of Care in HIV Management? Gordon Dickinson, M.D., FACP Professor of Medicine and Chief Infectious Diseases, Miller School of Medicine

Short Answer: NO

But 15-20 HPV types are oncogenic and linked to cervical cancer (especially 16 &18, but also 31, 33, 35, 39, 45, 51, 52, 58). Same strains infect anal mucosa. Anal cancer is increased in MSM So, anal screening may be a cost effective, life-saving procedure just as it is for women with cervical HPV.

HPV and Anogenital Warts Perianal warts HPV 6 and 11 responsible for >90% of anogenital warts 1 Peak prevalence 2 Women 20 24 years of age (6.2/1,000 person years) Men 25 29 years of age (5.0/1,000 person years) Clinically apparent in ~1% of sexually active US adult population 3 1. Jansen KU, Shaw AR. Annu Rev Med. 2004;55:319 331. 2. Insinga RP, Dasbach EF, Myers ER. Clin Infect Dis. 2003;36:1397 1403. 3. Koutsky L. Am J Med. 1997;102:3 8.

CERVICAL CANCER/ANAL CANCER BOTH RELATED TO HPV BOTH PRECEDED BY INTRAEPITHELIAL LESIONS BOTH ARISE IN THE TRANSFORMATION ZONE - JUNCTURE BETWEEN COLUMNAR EPITHELIUM RECTUM AND THE SQUAMOUS EPITHELIUM OF ANUS

CERVICAL CANCER/ANAL CANCER INCIDENCE OF CERVICAL CANCER PRE PAP SMEAR SCREENING 40-50 CASES /100,000 INDIVIDUALS

CERVICAL CANCER/ANAL CANCER INCIDENCE OF CERVICAL CANCER PRE PAP SMEAR SCREENING 40-50 CASES /100,000 INDIVIDUALS INCIDENCE OF CERVIVAL CANCER POST- PAP SMEAR SCREENING 8-10 CASES/100,000 INDIVIDUALS

CERVICAL CANCER/ANAL CANCER INCIDENCE OF CERVICAL CANCER PRE PAP SMEAR SCREENING 40-50 CASES /100,000 INDIVIDUALS INCIDENCE OF CERVIVAL CANCER POST- PAP SMEAR SCREENING 8-10 CASES/100,000 INDIVIDUALS BEFORE HIV EPIDEMIC, INCIDENCE OF ANAL CANCER 37 CASES/100,000 AMONG MEN WHO HAVE SEX WITH MEN(MSM) INCIDENCE OF ANAL CANCER IS EVEN HIGHER AMONG HIV-POSITIVE MEN AND WOMEN (J Natl Cancer Inst 2000; 92:1500-10)

CERVICAL CANCER/ANAL CANCER RELATIVE RISK OF INVASIVE ANAL CA WAS 37 IN HIV POSITIVE MEN AND 6.8 IN HIV POSITIVE WOMEN COMPARED TO THE GENERAL POPULATION (US AIDS CANCER REGISTRY MATCH STUDY)

CERVICAL CANCER/ANAL CANCER RELATIVE RISK OF INVASIVE ANAL CA WAS 37 IN HIV POSITIVE MEN AND 6.8 IN HIV POSITIVE WOMEN COMPARED TO THE GENERAL POPULATION (US AIDS CANCER REGISTRY MATCH STUDY). IN SAN FRANCISCO, CALIFORNIA, THE INCIDENCE OF ANAL CA AMONG ALL WHITE AND HISPANIC MEN AGED 40-60 Y/O RANGED FROM 3 CASES/100,OOO INDIVIDUALS IN 1973-1979 TO >14 CASES/100,000 INDIVIDUALS IN 1996-1999. 94 CASES OF ANAL CA IN MEN AND 27 IN WOMEN IN ALL AGE GROUPS WAS REPORTED IN 1995-1999, FOR SAN FRANCISCO COUNTY.

HUMAN PAPPILOMAVIRUS(HPV) ONE OF THE MOST COMMON SEXUALLY TRANSMITTED AGENT HIGHLY PREVALENT IN HIV-INFECTED PATIENTS MULTIPLE HPV TYPES COINFECTION FOUND IN CYTOLOGY

HUMAN PAPPILOMAVIRUS(HPV) LIKE CERVICAL HPV INFECTION, CERVICAL INTRAEPITHELIAL NEOPLASIA (CIN) AND CEVICAL CA, ANAL HPV INFECTION IS AN IMPORTANT RISK FACTOR FOR ANAL INTRAEPETHELIAL NEOPLASIA (AIN) AND ANAL CANCER.

HUMAN PAPPILOMAVIRUS(HPV) LIKE CERVICAL HPV INFECTION, CERVICAL INTRAEPITHELIAL NEOPLASIA (CIN) AND CERVICAL CA, ANAL HPV INFECTION IS AN IMPORTANT RISK FACTOR FOR ANAL INTRAEPETHELIAL NEOPLASIA (AIN) AND ANAL CANCER. MEN- PREVALENCE OF HPV 60% HIV NEG. MSM AND 93% IN HIV + MSM. (JID 1998; 177:361-7) WOMEN- 76% OF 223 HIV + WOMEN HAD ANAL HPV AS DID 42% OF HIGH RISK HIV NEG. WOMEN ( IVD, SEX WORKERS) (WOMEN S INTERAGENCY HIV STUDY) ANAL HPV INFECTION IS MORE COMMON THAN CERVICAL HPV INFECTION AMONG BOTH HIV + AND HIGH RISK HIV NEG WOMEN. (WOMEN S INTERAGENCY HIV STUDY)

Classification Terminology for Cervical Cytology: The 2001 Bethesda System Normal 1 ASCUS 2 LSIL 3 HSIL 3 Two types of atypical squamous cells (ASC) 4 Atypical squamous cells of undetermined significance (ASCUS) Atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesions (ASC-H) Squamous intraepithelial lesions (SIL) 4 Low-grade SIL (LSIL): Mild dysplasia, cervical intraepithelial neoplasia 1 (CIN 1) High-grade SIL (HSIL): Moderate and severe dysplasia, CIN 2/3, carcinoma in situ (CIS)

ANAL INTRAEPITHELIAL NEOPLASIA (AIN) AS IN THE CERVIX, ANUS DISPLAYS CHANGES RANGING FROM AIN I TO III. ANAL CYTOLOGY ASCUS- ATYPICAL SQUAMOUS CELLS OF UNKOWN SIGNIFICANCE; NON SPECIFIC IN CYTOLOGY BUT OFTEN ASSOCIATED W/ AIN ON HIGH RESOLUTION ANOSCOPY (HRA) AIN I - NOT THOUGHT TO PROGRESS DIRECTLY TO ANAL CA (LOW GRADE SQUAMOUS INTRAEPITHELIAL LESION/LSIL) AIN II AND AIN III - LIKELY TRUE PRECURSORS TO ANAL CA (HIGH GRADE SQUAMOUS INTRAEPITHELIAL LESION/HSIL)

ANAL INTRAEPITHELIAL NEOPLASIA(AIN) IN A STUDY FROM SAN FRANCISCO (J AIDS HUM RETROV 1998;17:314-9) 2 YEAR F/U ANAL CYTOLOGY

ANAL INTRAEPITHELIAL NEOPLASIA(AIN) IN A STUDY FROM SAN FRANCISCO (J AIDS HUM RETROV 1998;17:314-9) 2 YEAR F/U ANAL CYTOLOGY NO ANAL DX BASELINE 32% HIV POSITIVE PROGRESSED AIN I 9% HIV NEG. PROGRESSED TO AIN I AIN I BASELINE 30% OF PATIENTS HAD F/U NORMAL CYTOLOGY, ALL HIV NEG. > 50% HIV + MEN DEVELOPED AIN II OR III IN A STUDY FROM SEATTLE ( AIDS 1995; 9:1255-62) MSM W/ NO ANAL DX AT BASELINE 15% HIV POSITIVE DEVELOPED AIN II OR III/21 MONTHS VS 8 % HIV NEG.

SAN FRANCISCO FOUR YEAR INCIDENCE OF AIN II AND III IN HIV POSITIVE MSM AND HIV NEG. MSM(CID 2002; 35:1127-34)

ANAL INTRAEPITHELIAL NEOPLASIA(AIN) HIV POSITIVE WITH OR WITHOUT HISTORY OF ANAL INTERCOURSE 50 HIV+ (36 MEN, 14 WOMEN) ANAL HPV DNA WAS DETECTED AS FREQUENTLY IN PATIENTS REPORTING NO ANAL INTERCOURSE AS IN MSM (EUR J DERMAT 2003, 13:367-71) 36 MEN HIV POSITIVE, NO H/O RECEPTIVE ANAL INTERCOURSE PREVALENCE HPV 33% AND AIN 23% (JID 2004, 190;:1685-91) 50 HIV-INFECTED PATIENTS, IVDU, DENIED ANAL INTERCOURSE 67 HIV POSITIVE MSM HIV+/ IVDU PREVALENCE ANAL HPV 46%; AIN 36% PREVALENCE OF AIN II OR III DID NOT DIFER AMONG THE 2 GROUPS (ANN INTERN MED 2003, 183:453-59)

ANAL INTRAEPITHELIAL NEOPLASIA(AIN) ONCE AIN II OR III IS FOUND IN THE ANAL EPITHELIUM IT RARELY REGRESSES EVEN IN HIV NEG. INDIVIDUALS.

ANAL INTRAEPITHELIAL NEOPLASIA(AIN) ONCE AIN II OR III IS FOUND IN THE ANAL EPITHELIUM IT RARELY REGRESSES EVEN IN HIV NEG. INDIVIDUALS. THERE HAS BEEN NO STUDY THAT HAS ESTABLISHED THE RATE OF PROGRESSION FROM AIN II OR III TO ANAL CA; IT LIKELY REQUIRES DECADES. THERE HAS BEEN EXTENSIVE EXPIRIENCE WITH BOWEN DX (PERIANAL AIN II OR III) OF WHICH 5% OF LESIONS UNDERGO MALIGNANT CHANGES.

ANAL INTRAEPITHELIAL NEOPLASIA(AIN) ONCE AIN II OR III IS FOUND IN THE ANAL EPITHELIUM IT RARELY REGRESSES EVEN IN HIV NEG. INDIVIDUALS. THERE HAS BEEN NO STUDY THAT HAS STABLISHED THE RATE OF PROGRESSION FROM AIN II OR III TO ANAL CA; IT LIKELY REQUIRES DECADES.

CURRENT DATA THE INCIDENCE OF ANAL CANCER CONTINUES TO INCREASE DESPITE HAART. (AIDS 2005; 19:1407-1414)

HSIL LSIL ASCUS Normal Unsatisfactory Declined 50% 45% 40% 35% 30% 25% 20% 15% 10% 5% 0%

100% 80% 60% 40% 20% Ca in situ AIN II/III AIN I Normal 0% ASCUS LSIL HSIL

MIAMI VA MEDICAL CENTER EXPERIENCE Screening was accepted by patients. High rate of unsatisfactory specimens as providers became proficient. A successful screening program requires collaborative efforts of pathologists and proctologists.

Conclusion Persons with HIV disease as a group are at increased risk for both anal HPV infection and anal cancer. Based upon current knowledge of HPV and anal cancer in this population, Screening is indicated. The answer to the question should anal pap smears become a standard of care? Should change to YES.