Research opportunities and challenges in the Dominican Republic

Carolina Abuelo MD MSc, HIV Medical Association Clinical Fellow

Providence, RI

Abnormal Pap smears in Santiago

_ Location, location, location!_ Cervical cancer_ HIV_ Pap smears_ Methods_ Ethics

Santiago

Hospital Regional Universitario José Maria Cabral y Báez

Cervical cancer

_ leading cause of cancer deaths in women in developing countries is cervical CA.

_ 83% of cervical CA occur in locations without access to Pap smears

_ most common cause of years of life lost in Latin America and the Caribbean

_ DR 54% of eligible women screened in 2002 _ 1032 incident cases, about 562 die annually

Estimated age standardized incidence rates of cervical CA in Latin America and Caribbean, 2002

Worldwide prevalence of HPV infection is estimated to be between 9% and 13% (all ages) WHO dataEstimated prevalence of HPV infection in selected geographic areas (30-45 years old)

13.3%2

Ontario, Canada

14.5%3

Morelos State, Mexico

16.6%4

Concordia, Argentina

15.3%5

Reims, France

40.2%–41.6%6

Harare, Zimbabwe

18%*,7

Shanxi Province, China

Georgios Papanikolaou

_ Γεώργιος Παπανικολάου _ 05/13/1883-02/19/1962 _ presented his results in 1928 in Battle Creek,

Michigan_ 1941: test to detect cancer

Pap Smear

HPV and HIV

_ Cervical high risk neoplasia is correlated with HPV

_ cervical CA is a criterion for the diagnosis of AIDS as stage C disease

_ In a large US multicenter study of the natural history of HIV infection and related diseases to women, cervical cytology was found to be abnormal in 38.3% of HIV+ women.

Risk factors for abnormal Pap

_ CD4 count, HIV RNA level, detection of HPV, and number of male sex partners within 6 months of enrollment

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)

Terminology for Cervical Cytology (Bethesta)

NormalASCUS LSIL

HSIL

Follow up for abnormal Pap smear . . .

HIV in the DR

_ DR is one of the countries where the HIV epidemic is generalized

_ unpublished data from 2007 reveals HIV positivity at Cabral y Baez of 2.76% from a total of 7,782 men and women tested

Primary Aims:

_ To assess the prevalence of abnormal Pap smear among HIV + women in Santiago.

_ To assess the persistence of abnormal Pap smear among HIV + women in Santiago.

Secondary Aim:

_ To collect information on risk factors (low CD4 count, high plasma viral load, antiviral therapy, number of sexual partners, use of condoms, smoking) associated with cervical HPV infection.

Methods

_ retrospective chart review of 100 HIV + since 2003

_ Pap smears reported according to the 2001 Bethesda System

_ The prevalence of abnormal pap smear = total number of abnormal pap smears/total number of charts reviewed.

Incidence versus Persistence

_ Because fewer than 50 women have had more than 1 Pap, it is not possible to determine incidence, defined as a normal Pap is followed by an abnormal Pap.

_ persistence of abnormal Pap: women with abnormal Pap followed with colposcopy for low grade squamous intraepithelial lesions (LGSIL) or higher.

_ For this study, persistence is defined as two consecutive abnormal Pap smears.

Nitty Gritty

_ 226 women with Pap smears. _ 100 randomly selected _ unsatisfactory pap smears or vaginal cytology will be

excluded. _ demographic data abstracted_ risk factors will be collected: CD4, plasma viral load,

HAART, number of sexual partners, use of condoms, history of STI, gravidity, and smoking.

_ Information about the cytology and follow up will be recorded.

Analysis:

_ univariate analysis will be used to determine which variables are associated with abnormal cytology.

_ association between abnormal follow-up smears and demographic and clinical predictors will be examined using logistic regression.

_ SAS 9.1

Challenges, Part I

Challenges, Part II

_ Mal olor en el hospital Jose Maria Cabral y Baez_ viernes 9 de enero de 2009_ Pacientes del Hospital regional Y universitario

Jose Maria Cabral Y Baez presentaron este viernesquejas por el mal olor que sale de la morgue.Se dice que el olor a descomposicion es tan fuerteque sube hasta el 4to piso. se dice que la razonde aquel mal olor es por que los frezers quemantienen los cuerpos de los cadaveres estandescompuestos.

Fly in the ointment: IRB challenges

_ Permission from multiple places _ Language issues_ For interventions need consent forms

Additional Resources

_ Micah Johnson, Brown Medical Student (Micah_Johnson@brown.edu)

_ Pequeños Pasitos, James Craig Pickard and Rita Josefina Rizek (info@amotherswish.org )

Thank you

_ Susan Cu Uvin, MD_ Tim Flanigan MD_ Claudia Rodriguez MD_ Mike Stein MD_ Brown University Global Health Scholarship

References_

[i] Solomon D, Davey D, Kurman R, Moriarty A, O'Connor D, Prey M, Raab S, Sherman M, Wilbur D, Wright TJ, Young N. The 2001 Bethesda System.Terminology for reporting results of cervical cytology. JAMA. 2002;287:2114–2119.

_ [i] Schiffman M, Castle PE. The promise of global cervical-cancer prevention. N Engl J Med. 2005;353:2101-2104._ [ii] Yang BH, Bray FI, Parkin DM, Sellors JW, Zhang ZF. Cervical cancer as a priority_ for prevention in different world regions: an evaluation using years of life lost. Int J Cancer 2004;109(3 (April)):418–24._ [iii] Murillo R, Almonte M, Pereira A, et al. Cervical Cancer Screening Programs in Latin America and the Caribbean.

Vaccine 26S (2008) L37–L48._ [iv] http://www.who.int/healthinfo/survey/whsdom-dominicanrepublic.pdf_ [v] WHO/ICO Information Centre on HPV and Cervical Cancer (HPV Information Centre). Summary_ report on HPV and cervical cancer statistics in Dominican Republic. 2007. [12/02/08]._ Available at www. who. int/ hpvcentre_ [vi] P Schuman, SE Ohmit, RS Klein, et al. Longitudinal Study of Cervical Squamous Intraepithelial Lesions in Human

Immunodeficiency Virus (HIV)–Seropositive and At-Risk HIV-Seronegative Women. Journal of Infectious Diseases, 2003; 188: 128-36.

_ [vii] From the Centers for Disease Control and Prevention. 1993 revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. JAMA. 1993 Feb 10;269(6):729-30

_ [viii] Massad, L, Riester, K, Anastos, K et al. Prevalence and predictors of squamous cell abnormalities in papanicolau smears from women infected with HIV-1. Journal of Acquired Immune Deficiency Syndromes. 1999; 21 (1) 33-41.

_ [ix] Veras, B. Prevalencia de Casos positivos de VIH en pruebas realizadas en el Hospital Jose Ma. Cabral y Baez, Santiago, Rep. Dom., 2007. Boletin Notas de Epidemiologia Vol No.5. Octubre 2008