Screening & Management of Anal Dysplasia in the HIV Clinic

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Project ECHO - UNM Indian Country HIV TeleECHO Screening & Management of Anal Dysplasia in the HIV Clinic 9/8/2021 Clinical Director, SCAETC Professor, Dept of IM, Div of ID, UNMHSC Michelle Iandiorio, MD Version_ 09 2021 1 Conflict of Interest Disclosure Statement Speaker has nothing to disclose. This presentation was reviewed by UNMHSC and SCAETC faculty to ensure it meets Continuing Education guidelines. This project is supported by the Health Resources and Services Administration (HRSA) of the U.S. Department of Health and Human Services (HHS). Under grant number U1OHA33225 (South Central AIDS Education and Training Center). It was awarded to the University of New Mexico. No percentage of this project was financed with non-governmental sources. This information or content and conclusions are those of the authors and should not be construed as the official position or policy of, nor should any endorsements be inferred by HRSA, HHS, or the U.S. Government. 2 Learning Objectives Recognize that people with HIV (PWH) are at considerably higher risk for anal dysplasia and cancer. List anal cancer screening methods recommended for PWH. Identify recommended follow-up for those with abnormal screening anal cytology. 3 Anal Cancer 8,300 in the U.S. Many fold (37-100) increase among people with HIV Very high morbidity, quality of life issues https://www.cdc.gov/cancer/dcpc/data/ https://theconversation.com/how-the-anal-cancer-epidemic-in-gay-and-bi-h... A study of American adults estimated the incidence of anal cancer per 100,000 people between 1996 and 2007. 4 Anal Cancer Risk Factors High risk human papilloma virus (HPV) infection Smoking Compromised immune function (including HIV), autoimmune, transplant Multiple sex partners Anal warts Chronic inflammation Previous history of dysplasia (anal or cervical) Silverberg, M et al. Risk of anal cancer in HIV-infected and HIV-uninfected individuals in North America. CID. 2012;54(7):1026-1034. Palefsky, JM. et al, Obstet Gynecol Clin N Arm, 2009;36: 187-200. Blomberg, M et al, JID, 2012, May 15; 205: 1544-53. https://www.cdc.gov/cancer/cervical/basic_info/risk_factors.htm Cervical: 5+ years birth control pills, 3+ children 5 Few at Risk are Receiving Anal Cancer Screening U.S. MSM with HIV rates as much as 37-fold higher than the general population One in 10 MSM in care for HIV are screened for anal cancer Healthcare disparities in accessing screening Less common in blacks , those with less than high school education, those followed by smaller medical practices Freedman, M. Prevalence of Anal Pap testing Among Men in HIV Medical Care who Have Sex with Men, United States, 2009-2012. ID Week, October 27, 2016, New Orleans. MSM = men who have sex with men Freedman, M. Prevalence of Anal Pap testing Among Men in HIV Medical Care who Have Sex with Men, United States, 2009-2012. ID Week, October 27, 2016, New Orleans. Compared with white men, non-Hispanic blacks had a significantly lower pap testing rate (7% versus 13% A total of 8514 men were classified as MSM and had both interview and medical record data. An estimated 11% (95% confidence interval [CI] 9-13) of HIV-infected of MSM overall received anal pap testing in the 12 months before interview.....lower in men with less than a high school education.... Men seen in a medical practice with more than 400 patients had a higher testing rate (14%) than those seen in practices with 50 to 400 patients (9%,P= 0.1) or fewer than 50 patients (4%,P< 0.0001). 6 Human Papilloma Virus (HPV) Most common sexually transmitted infection: 75-80% of people exposed Most immunocompetent people clear HPV infection but if it persists, it can lead to dysplasia/cancer HIV: Less clearance, multiple strains of HPV, accelerated progression to dysplasia Women: HIV neg: 40% anal HPV, 43% cervical HPV PWH: 76% anal HPV, 43% cervical HPV Men: HIV neg: 60% anal HPV PWH: nearly all with history of receptive anal sex Hariri, S et al. JID 2011. 204(4):566-73. Konopnicki, D et al. JID 2013, doi:10.1093/infdis/jit090. X-Wu Sun, et al. NEJM 1997, 337:1343-9. www.cancer.gov/cancertopics/factsheet/risk/hpv Additional optional reference: Chin-Hong & Palefsky, 2005. HIV+ MSM: Higher burden of HPV infection, Multiple HPV subtypes, More likely to develop Anal Intraepithelial Neoplasia (AIN) than HIV negative Relationship between decreased immune function and higher rates of anal and cervical HPV infection Not any direct effect of HIV, rather, related to immune dysfunction Double-stranded DNA virus that replicates in the nucleus of squamous epithelial cells, thus its link with cervical, anogenital, and oral sites. Single layer of flat cells with rapid diffusion. Hundreds of papillomavirus types are capable of infecting humans. Most cases of anal cancer are linked to infection by HPV-16, which is closely associated with cervical cancer. The infection is initiated by an opening in the skin, allowing virus entry and access to binding sites. Once the virus binds, it is brought into (endocytosed) into the host cell. Replication of the virus is closely associated with the differentiation state of the host squamous epithelial cell. https://www.cdc.gov/hpv/hcp/ https://www.uptodate.com/contents/virology-of-human-papillomavirus-infec... http://microbiollogy.blogspot.com/2013/05/virology_8.html 7 HPV and Immunosuppression Inverse relationship between measures of immunity and HPV for HIV-infected women As CD4 cell count drops (and viral load increases), prevalence of HPV infection increase Studies show a higher rate of oncogenic HPV infections in women with lower CD4 cell counts Role of antiretroviral (ARV) therapy, immune reconstitution, and HPV Jury still out ARV therapy (so far) has not been shown to prevent progression of dysplasia Speaker notes: High viral loads and low CD4 cell counts among women with HIV have been associated with HPV infection in multiple studies. Immune reconstitution with ARV therapy has not been shown in studies to lower rates of HPV progression to cancer unlike other conditions and diseases associated with the later stages of HIV infection. 8 Anal Cancer Screening in HIV No national guidelines Annual digital anal rectal exam (DARE) recommended (BIII) Anal cytology only IF high-resolution anoscopy (HRA) available If ASCUS or greater, HRA indicated (BIII) r https://aidsinfo.nih.gov/contentfiles/lvguidelines/glchunk/glchunk_343.pdf https://aidsinfo.nih.gov/contentfiles/lvguidelines/glchunk/glchunk_343.pdf 11/2018 "AIN are recognized through visual inspection, including HRA and bx as needed. A DRE to feel for masses should be performed as part of routine evaluation. 2/2016 "Anal cytology screening should not be done without the availability of referral for HRA. Berry, et al. Anogenital neoplasia and HIV. HIV InSite. Nov 1998. Some experts recommend annual anal cytology for those at risk. Aberg, JA, et al. CID 2013. MSM, women with hx receptive anal intercourse or abn cervical pap, and all HIV with genital warts should have anal ap. At THS, The current guidelines for patient's living with HIV is to screen for anal dysplasia with an annual digital anorectal screen (dare) for all patients 35 years old and those <35 with symptoms of anal cancer. This is done with an Anal Papanicolaou with cytology.A baseline test should be obtained, and if normal be performed annually thereafter. 9 Anal Cancer Screening Perianal & anal exam Important in men & women Visualize external lesions Masses may be palpated by DRE Symptom review Anal bleeding Anal itching, pain Anal discharge Narrowing of stool Mass in anus Image from www.hpvvaccination.com Cervical cancer often has no signs or symptoms. In advanced disease, may cause bleeding or discharge 10 HPV Infection & Detection by Anal Cytology Men and women with HIV are at higher risk of developing squamous cell cancer of the anus (especially MSM) It is possible that screening HIV-infected patients with anal Pap smears will decrease the morbidity and mortality associated with anal cancers and dysplasia Evidence in support of performing routine anal Pap smears not availableyet, but some guidelines recommend anal Pap tests at baseline and annually for: MSM Any patient with history of anogenital warts Women with abnormal cervical or vulvar histology Speakers Notes Inform participants that although the discussion in this training is about screening for cervical cancer, the idea of conducting anal Pap smears for HIV-infected patients has recently gained momentum. Anal and cervical cancers in HIV-infected patients Anal and cervical cancers are associated with high-risk types of HPV infection. The rates of anal cancer among MSM are comparable to the incidence of cervical cancer in women before the introduction of routine Pap smears (35/100,000) (Chaio et al., 2006). The rates of anal cancer among HIV-infected MSM are about double what they are for non-HIV infected men. Anal Pap smears are about as accurate in detecting pre-cancerous cells as cervical Pap smear. Anal Pap smears involve inserting a swab blindly into the canal and fixing for cytological examination. Anal cytology is defined by the Bethesda system as well and abnormal results are evaluated by high-resolution anoscopy and biopsy to produce a diagnosis. Recommendations on the utility of anal Pap smears Literature on the utility of anal Pap smears for HIV-infected individuals is limited due to the lack of published randomized clinical trials data looking at anal Pap smears. Stay tuned to developments and changes as data becomes available on whether performing anal Pap smears should be a part of routine healthcare for our HIV-infected patients. As of 2007, the New York State AIDS Institute recommends that providers conduct anal Pap smears for MSM, any patient with anogenital warts, and women with a history of cervical or vulvar histological abnormality. If providers want to consider anal Pap smears, they should be sure to coordinate follow-up with a practice that is capable or conducting high-resolution anoscopy. 11 J Am Osteopath Assoc. 2011;111(3_suppl_2):S35-S43. The anal canal is approximately 4 cm long from the anal verge (margin) to the transitional zone. The dentate line (also called the pectinate line) is located at the proximal end of the anus. The flat squamous cells of the anal canal end here. The transitional (transition, transformation) zone has been considered synonymous with the dentate line owing to their proximity, but the transitional zone is actually just proximal to the dentate line, is considered part of the anus, and contains cube-shaped cells called transitional cells. It is the junction between rectal columnar epithelium and anal squamous epithelium, similar to the cervical transitional zone. Above the transitional zone is the rectum with its columnar epithelium. Adapted from Netter. 5 12 Anal PAP Smear/Cytology Blind-sample swab Moistened Dacron swab Insert swab 2-3 inches into anal canal Gentle pressure in 360 degrees while withdrawing over 30 seconds Blind swab (unlike cervical swab which is visualized during speculum exam) Goal: sample at dentate line, where rectal mucosa and squamous mucosa meet Wenoah Veikley,, ACRN: "Longer than you or patient are comfortable with" An anal Papanicolaou is a simple test which detects abnormal cells which that may be a possible precursor of anal cancer, and can determine need for referral for HRA and further intervention The anal pap can be done by a clinician, or by the patient via self collection. Studies have shown that anal self-sampling and accuracy was similar to that of clinician sampled specimens. 13 Anal Cytology Nomenclature Normal (negative for intraepithelial lesion or malignancy) LSIL (low-grade squamous intraepithelial lesion) or AIN (anal intraepithelial neoplasia grade 1) HSIL (high-grade squamous intraepithelial lesion) or AIN2, 3 (anal intraepithelial neoplasia grade 2,3) ASCUS (atypical squamous cells of undetermined significance) ASC-H (atypical squamous cells, cannot rule out a high-grade lesion) 14 Cytology Image from Id.medicine.ucsf.edu Squamous cell abnormalities Atypical squamous cells Atypical squamous cells of undetermined significance (ASC-US) Atypical squamous cells cannot exclude HSIL (ASC-H) Low grade squamous intraepithelial lesion (LGSIL or LSIL) HPV/mild dysplasia/CIN 1 High grade squamous intraepithelial lesion (HGSIL or HSIL) CIS, CIN 2, CIN 3; invasiveness Superficially invasive squamous cell carcinoma (SISCCA) 15 Anal PAP Illustration taken from Luc Latulippe Copyright 2005. J Am Osteopath Assoc. 2011;111(3_suppl_2):S35-S43. https://www.ihs.gov/sites/hivaids/themes/responsive2017/display_objects/... 16 References https://www.hivguidelines.org/hiv-care/anal-dysplasia-cancer/ Introduction of human papillomavirus vaccination programmes: Updated systematic review and meta-analysis. Lancet 2019; 394(10197):497-509 Abramowitz L, Benabderrahmane D, Ravaud P, et al. Anal squamous intraepithelial lesions and condyloma in HIV-infected heterosexual men, homosexual men and women: prevalence and associated factors. AIDS 2007;21(11):1457-1465 Tamelet C, Ravaux I, Dhiver C, et al. Feasibility and Acceptability of Anal Self-Sampling for Human Papillomavirus Screening in HIV-Infected Patients. Intervirology 2016;59:118-122. Cranston RD, Darragh TM, Holly EA, Jay N, Berry JM, Da Costa M, Efird JT, Palefsky JM: Self-collected versus clinician-collected anal cytology specimens to diagnose anal intraepithelial neoplasia in HIV-positive men. J Acquir Immune Defic Syndr 2004;36:915-920. Rosenberg JG, Dodge B, Van der Pol B, Reece M, Herbenick D, Fortenberry JD: Reactions to self-sampling for ano-rectal sexually transmitted infections among men who have sex with men: a qualitative study. Arch Sex Behav 2011;40:281-288. Bnard , Prez N, Brisson M; HPV Vaccination Impact Study Group. Population-level impact and herd effects following the introduction of HPV vaccination programmes: updated systematic review and meta-analysis. Lancet. 2019;394(10197):497-509. http://www.idsociety.org/Guidelines/Patient_Care/IDSA_Practice_Guideline... Guidelines for the Prevention & Treatment of Opportunistic Infections in HIV-infected Adults & Adolescents. https://aidsinfo.nih.gov/guidelines/html/4/adult-and-adolescent-opportun... https://www.ihs.gov/sites/hivaids/themes/responsive2017/display_objects/... 18 Resources National Clinician Consultation Center http://nccc.ucsf.edu/ HIV Management Perinatal HIV HIV PrEP HIV PEP line HCV Management Substance Use Management Present case on ECHO http://echo.unm.edu [email protected] AETC National HIV Curriculum https://aidsetc.org/nhc AETC National Coordinating Resource Center https://targethiv.org/library/aetc-national-coordinating-resource-center-0 Additional trainings [email protected] www.scaetc.org Find additional TeleECHO sessions in your area: https://echo.unm.edu/locations-2/echo-hubs-superhubs-united-states/ https://hsc.unm.edu/echo/get-involved/join-an-echo/ IDEA Platform: Infectious Diseases Education & Assessment. https://idea.medicine.uw.edu/ AETC National HIV Curriculum: 6 core modules for self study; regularly updated; CME, CNE Hepatitis C Online Curriculum: https://www.hepatitisc.uw.edu/ Hepatitis B Online Curriculum: https://www.hepatitisb.uw.edu/ National STD Curriculum: https://www.std.uw.edu/ 19