CHICAGO—The study that received more attention than any other at this year's ASCO Annual Meeting was the report of an effective, affordable way to screen for cervical cancer in low-income countries, using visual inspection with acetic acid—vinegar (Abstract 2). The large clinical trial conducted in Mumbai, India, found that the plan reduced the rates of cervical cancer, the most common cancer among women in developing countries and the number one cause of cancer death in women in India, by nearly one-third. In a widely reported estimate, the researchers said this translated to the potential to prevent 22,000 cervical cancer deaths in India every year and 73,000 such deaths in resource-poor countries worldwide.
The lead researcher, Surendra Srinivas Shastri, MD, Professor of Preventive Oncology at Tata Memorial Hospital in Mumbai, explained that contrary to the situation in the United States and most developed countries where the Pap test is now routine, there is no screening program for cervical cancer in resource-poor countries. Pap smear screening is not feasible because of inadequate infrastructure, lack of trained personnel, logistic difficulties, and its relatively high cost.
“We hope our results will have a profound effect in reducing the burden of cervical cancer in India and around the world,” he said.
“This is the first trial to identify a cervical cancer screening strategy that reduces mortality and is feasible to implement on a broad scale throughout India and in other developing countries. Our trial used primary health care workers who can easily access women in the community, which is critical in India and other countries that lack sufficient nurses, physicians, and laboratory facilities.”
He added that the team is already working with state and national health authorities in India to make the screening strategy and health education available to women throughout the country.
Indian health officials in Maharashtra state, where the trial was conducted, are preparing to train primary health care workers to provide the screening to all women 35 to 64 years old there—including women who participated in the study—at the same 24 month interval explored in the trial. In addition, the Indian government is working to implement the screening country-wide and has plans to reach out to other low to moderate income countries to inform them of these results and offer training resources, Shastri said.
The Discussant for the study, Electra Paskett, PhD, Professor of Cancer Research and Associate Director for Population Sciences at Ohio State University, called screening via visual inspection with acetic acid (VIA) “validated, acceptable, cheap, implementable, and generalizable.”
“In low-resource countries it can save lives,” she said. “How many lives can be saved annually? I think we could save 250,000 lives per year worldwide.”
In the study, women aged 35 to 64 from 20 “slum clusters” in Mumbai who had no prior history of cancer were randomly assigned to have either the screening every two years (75,360 women) or no screening (76,178 women), which is the current standard of care in India.
Women in the control group received one round of cancer education and were asked to report to the primary health workers any signs or symptoms of cervical cancer that they noticed on the basis of what they had learned during the initial cancer education sessions. The health workers then directed them to the Tata Memorial Hospital, where they underwent diagnosis and treatment at no cost, or to other nearby facilities of their choice.
The screening group received four rounds of the screening and cancer education at 24-month intervals between 1998 and 2010. All trial participants who were diagnosed with cervical cancer were offered free treatment.
The visual inspection test is performed by applying vinegar to the cervix using a cotton swab. After 60 seconds, the cervix is examined with the naked eye using a lamp. Pre-cancerous tissue turns white when vinegar is applied, whereas healthy tissue does not change color. The results are known immediately—a very important advantage in rural areas where women might otherwise have to travel for hours to see a doctor, Shastri noted.
An expert gynecologist randomly rescreened approximately five percent of the participants using the technique, with excellent agreement with the findings of the primary health workers, Shastri reported.
Screening with VIA resulted in a 31 percent reduction in cervical cancer-specific death rates (11.1 and 16.2 per 100,000, respectively). There was also a seven percent reduction in the overall mortality rate because cancer was often diagnosed at an earlier stage, although the difference in the overall death rate was not statistically significant, he said.
The incidence of invasive cervical cancer was comparable in the two groups — 26.7 per 100,000 in the screening group and 27.5 per 100,000 in the control group). This suggests that screening did not lead to overdiagnosis, “which is a huge problem in most screening programs,” Shastri said.
Before the trial began, “we talked to religious, political, and community leaders, and then talked to women to get informed consent, to ensure a sense of community, ownership, and good participation,” he said. The participation rate was high—89 percent in the screening group and 91 percent among controls. Treatment completion rates were also high: 86 percent in the treatment group and 72 percent in controls.
VIA was performed by primary health workers—local women with at least a 10th grade education and good communication skills—who received four weeks of intensive training at the beginning of the study, and a one-week refresher course every year. They were the only health professionals available to deliver VIA screening in remote, rural parts of India, he explained.
Speaking at an ASCO news conference about this and the other plenary studies, the moderator, Jyoti Patel, MD, Associate Professor in Medicine-Hematology/Oncology at Northwestern University Feinberg School of Medicine, said the study has tremendous implications for women around the world who have inadequate access to health care: “Utilizing primary health workers to detect curable cancer saves lives. It is easily implementable and scaleable. I congratulate the authors.”
Also at the news conference, Carol Aghajanian, MD, Chief of the Gynecologic Medical Oncology Service at Memorial Sloan-Kettering Cancer Center, acting as an ASCO spokesperson in this area, commented that Pap smear screening for precancerous cells has cut cervical cancer incidence and mortality by 80 percent in high-income countries.
“Pap smear screening is very successful and the mortality of cervical cancer in the U.S. is quite low. We have a good program in place in areas with fewer resources. Gynecologists do use the vinegar test and visualization. What is new is using these tests for screening in India,” she said.
Similarly, Paskett noted, the technique “could be an alternative in certain pockets of high incidence of cervical cancer even for women in the U.S. who do not have access to standard resources.”
Still, the greatest burden by far of cervical cancer is in less developed regions of the world. About 500,000 million women are diagnosed annually, and about 250,000 die from cervical cancer. About three-quarters of these cases are in developing countries and about one-third are in India, she said.
“The goal of cervical cancer prevention programs in developing countries is to maximize participation and screen women age 30 to 50 once or twice in their lifetime with a test that has maximum sensitivity, affordability, and feasibility. Cytologic testing is not realistic, and HPV testing is cost-prohibitive. VIA is simple and inexpensive and can be provided by trained, non-medical personnel.”
Previous studies have shown VIA to be accurate compared with Pap smear tests and that it finds more lesions likely to progress, compared with HPV testing, she said.
“The unique and important characteristics of the study are that it included a population from a low socioeconomic group, the slums of Mumbai, who had previously been unscreened. This community-friendly study used seven layers in the community to get permission to do the study. The primary agents of change were primary health workers and social workers.”
Essential diagnostic and treatment services were accessible to women in both arms of the study, she noted.
Nevertheless, there are some issues with the study, she noted: “There were reduced rates of screening over time, dropping from 68 to 54 percent. There was a low attrition rate, and not all women received all rounds of screening.”