Cervical Cancer

CERVICAL CANCER

Haiti has the highest reported incidence of cervical cancer of any country in the world, with 94 cases per 100,000 population. Cervical cancer is the leading cause of cancer death in Haitian women with an estimated 1,500 deaths annually. This is 50 times higher than the rate in the United States, where cytology based cervical screening with Pap tests has dramatically decreased cervical cancer mortality. Women in Haiti have not benefited from Pap test screening due to lack of health care infrastructure and trained pathologists; there are only four pathologists in this country of 10 million people. As a consequence, most women in Haiti have never been screened for cervical cancer.

The situation in other developing countries is similar. Cervical cancer remains a leading cause of mortality among women of reproductive age in the developing world. An estimated 500,000 new cases of cervical cancer will occur worldwide this year, with 85% of these occurring in resource-poor countries.

Progress in cervical cancer prevention is being made in Haiti and many other developing countries. The introduction of simple and cost effective “screen and treat” strategies and human papillomavirus (HPV) vaccination offer tremendous opportunity.

  • Cervical visual inspection with acetic acid (VIA) can detect early dysplastic (precancerous) lesions before the development of invasive cancer. The test can be performed by nurses, and treatment offered the same day with cryotherapy of the cervix. VIA has been successfully introduced into many developing countries with great success.
  • Rapid screening tests for cervical HPV infection may be even more effective. Squamous cell cancers of the cervix are causally linked with infection with HPV. Studies show that screening women for cervical HPV infection and treating HPV-positive women with cryotherapy decreases the incidence and mortality from cervical cancer.
  • The Global Alliance for Vaccines and Immunizations (GAVI) recently announced efforts to provide the HPV vaccine to 72 of the world’s poorest countries. Trials have shown that administration of this vaccine against high risk HPV, including types 16 and 18, reduced the incidence of both high risk HPV infection and HPV-related cervical intraepithelial neoplasia (CIN). GAVI is working to decrease the price of the vaccine and to develop programs for its administration in poor countries.

The Haitian Ministry of Health has made cervical cancer prevention a priority. Dr. Cynthia Riviere (pictured left) has opened a cervical cancer prevention clinic at the GHESKIO center in Port au Prince. “In Kreyol, we say that the mother is the ‘poto mitan’ of the family; that means the center pole that holds the entire family up. Haitian families can’t afford to lose their center pole. That’s why we need to prevent cervical cancer,” says Dr. Riviere.

She is also conducting research studies to determine optimal screening and prevention strategies for HIV infected women who are five times more likely to develop cervical cancer than women uninfected with HIV.

Dr. Riviere states, “Now that we have the tools, we need to put them to work, to protect Haitian women and to keep the poto mitan of the Haitian family standing strong.”

GHESKIO is conducting the following projects in cervical cancer prevention and treatment:

1. Epidemiology of HPV and feasibility of HPV vaccination. We are defining the prevalence, incidence, and types of HPV infection in 200 HIV negative women, in preparation for HPV vaccination programs. We are also conducting qualitative studies on the acceptability of HPV vaccination among young women, their parents, and community leaders.

2. The effect of early antiretroviral therapy on the natural history of cervical HPV infection and the incidence of pre-cancerous lesions: We are following a cohort of 450 HIV-infected women with annual PAP smears, HPV tests and colposcopy.  One half of the cohort initiated ART when they were asymptomatic with CD4 cell counts between 200-350 cells/mm3 and the other one half deferred ART until they had an AIDS illness or their cell count fell below 200 cells/mm3.  We are comparing the natural history of HPV infection and incidence of cancer in these two groups.

3. The effect of HIV and HIV/HPV co-infection upon PGE2 metabolism in women. We have enrolled HIV-infected and HIV-uninfected women with and without cervical dysplasia and collected cervical cells and urine. The expression of mRNA coding 11 proteins in the PGE2 metabolic pathway in cervical cells is being quantified by RNA seq transcriptome analysis and qRT PCR.  A urine metabolite of PGE2 is being quantified to measure systemic levels of PGE2. We will compare levels between HIV-infected and uninfected and between women with and without pre-cancerous lesions. The research has implications for the prevention of cervical cancer. If HIV-infection increases PGE2 metabolism in cervical cells, then drugs that block the metabolism of PGE2 (aspirin, COX-2 inhibitors) could potentially serve as cancer prophylaxis in HIV-infected women at high risk for cervical cancer.

4. Risk factors and biomarkers of recurrent precancerous cervical lesions after surgical therapy. We will follow a cohort of 200 HIV-infected women who have been diagnosed with precancerous cervical lesions (CIN2+) and treated with loop electro-excision procedure (LEEP). We will examine predictors of disease recurrence including: HIV status at time of LEEP (CD4 count, HIV viral load, WHO stage); HPV type in dysplastic lesion; histology grade of lesion; mRNA expression in cervical cells. This information will help determine the pathogenesis of recurrence and guide treatment of HIV-infected women with high grade lesions.

5. Operational studies of HPV vaccine strategies: Demonstration HPV vaccine projects in other poor countries have vaccinated adolescent girls in school based programs. This poses a challenge for Haiti, where ~50% of girls age 10 – 13 do not attend school. Girls who do not attend school in Haiti have earlier onset of sexual activity, are more likely to engage in high risk sexual activity (exchanging sex for food, services, or money), and therefore are more likely to acquire HIV and HPV. GHESKIO will pilot strategies to engage and retain adolescent girls who do not attend school in HPV vaccination programs in the slums adjacent to GHESKIO.

6. A randomized clinical trial of the “HPV screen and treat” strategy will be initiated at GHESKIO in 2013 in HIV-infected women with support from the NIH ACTG. Women will be screened for HPV infection of the cervix and if positive randomized to immediate cryotherapy (HPV screen and treat) or follow up by standard Pap test and colposcopy (US standard of care).

Please see GHESKIO’s Director of Cervical Cancer Prevention, Dr. Cynthia Riviere, featured in New York Presbyterian’s Cancer Prevention publication here.