Cervical Cancer Prevention: IARC/INCTR Joint Projects in Nepal and Tanzania

Doctors in Bhaktapur, Nepal, learn how to perform the loop electrosurgical excision procedure (LEEP) during a training course sponsored jointly by IARC and INCTR in March.

The International Agency for Research on Cancer (IARC), the cancer research agency of the World Health Organization (WHO) located in Lyon, France, is collaborating with the International Network for Cancer Treatment & Research (INCTR) in organizing cervical cancer prevention programs in Nepal and Tanzania where cervical cancer is the most common cancer among women.

Currently, more than 80% of the women diagnosed with cervical cancer in these countries present with locally advanced disease. Although early detection and effective treatment of cervical cancer precursor lesions will prevent the development of cervical cancer, there are currently no organized screening or early detection programs in Nepal and Tanzania as in many other developing countries. Furthermore, it is now widely recognized that cervical cytology-based screening is not feasible in these countries, due to limited manpower and financial resources.

IARC and INCTR are therefore working together with national institutions in both countries, to evaluate the role of alternative, low-technology approaches. Specific projects addressing these issues are supported by the Bill & Melinda Gates Foundation through the Alliance for Cervical Cancer Prevention (ACCP), of which IARC is a member, and by the WHO Regional Office for the African Region (WHO/AFRO). The participating institutions in Nepal are Bhakthapur Cancer Care Centre (BCCC), and the Nepal Network of Cancer Treatment and Research (NNCTR/INCTR), Banepa, both located near Kathmandu. The Ocean Road Cancer Institute (OCRI) in Dar es Salaam is the partner institution in Tanzania (see pgs 18-19). The prevention programs are coordinated by Dr R. Sankaranarayanan (IARC), Ms. Melissa Adde (INCTR), Dr A. Felipe (Jr) (AFRO), Dr Aarati Shah (BCCC, Bhakthapur), Dr Surendra Shrestha (NNCTR, Banepa) and Dr Twalib Ngoma (OCRI, Dar es Salaam).

The screening tests, using visual inspection with acetic acid (VIA) and visual inspection with Lugol’s iodine (VILI), are carried out by trained nurses and female health workers. VIA involves the application of 5% acetic acid to the cervix. Detection of a definite white area touching the squamocolumnar junction constitutes a positive test. Detection of yellow, non-iodine uptake areas in the transformation zone of the cervix, after application of Lugol’s iodine solution, constitutes a positive VILI test.

Doctors in Tanzania learn how to perform examinations with a colposcope during a training session sponsored jointly by IARC and INCTR.

The use of these services does not require a laboratory infrastructure, and the results are obtained immediately, allowing for investigation and treatment on the same day. The accuracy of the two methods in detecting high-grade cancer precursor lesions, and the effectiveness of simple treatment such as cryotherapy and loop electrosurgical excision procedure (LEEP), are being evaluated. Cryotherapy involves application of ice- cold metallic probes with surface temperatures below -65oC to the cervix, leading to the eventual destruction of the abnormal cells. LEEP is an excisional treatment using an electrically activated thin stainless steel wire loop electrode.

Five thousand women, aged 30-59 years, will be screened using VIA and VILI at each project site in Nepal. Those identified as positive, on one or both tests, will be investigated further with colposcopy, and biopsies will subsequently be taken in those with abnormal findings. Women with histologically confirmed cervical intraepithelial neoplasia grades 2 and 3 (CIN 2 and CIN 3), located on the ectocervix, without extension into the cervical canal will then be randomized to receive ‘single’- or ‘double-freeze’ cryotherapy treatment. ‘Single-freeze’ cryotherapy involves a single cycle of freezing of the cervix for three minutes, while ‘double-freeze’ involves two cycles of three-minute freezing, with an interval of five minutes. Comparison of the cure rates with the two methods will be carried out one year after treatment. If the ‘single-freeze’ treatment is found to be as effective as the ‘double-freeze’ method, it will lead to savings in costs. The findings from these two studies will be pooled with those from a large multicentre IARC study. Larger lesions that cannot adequately be covered by the cryoprobes, or lesions extending into the endocervix, will be treated by LEEP. The detection rates for high-grade lesions (per 1,000 women) associated with the screening tests will also be compared to indirectly assess the sensitivities of the tests.

A health worker explains the cervical screening program to women visiting the Ocean Road Cancer Institute in Tanzania.

In Tanzania, 5,000 women aged 25-59 years will be screened with VIA and VILI. All women will also be investigated by colposcopy (irrespective of the screening findings) and biopsies carried out in those with abnormalities. This study design will help to evaluate the sensitivity and specificity of the screening tests directly, without any verification bias. In this project, all grades of CIN lesion will be treated, either with cryotherapy or LEEP.

A regional training center for cervical cancer prevention has also been established at the Ocean Road Cancer Institute to facilitate the training of staff in all aspects of screening and treatment of cervical neoplasia, with the ultimate objective of catalyzing the development of such services in the region.

Women diagnosed with invasive cancer in these two programs will be referred for treatment in Bhakthapur and Kathmandu, or Dar es Salaam respectively, where surgical and radiotherapy services are available.

INCTR is also working with IARC on the publication and dissemination of simple practical manuals on VIA, VILI, colposcopy and treatment of cervical cancer precursor lesions. Nurses and doctors involved in the projects described above have been intensively trained in screening, colposcopy, cryotherapy and LEEP, in courses jointly organized by the IARC, INCTR and WHO/AFRO. The medical personnel will gain lots of experience as these projects progress over the next few months. It is hoped that they will eventually emerge as a core group of master trainers, facilitating further training and the expansion of preventive services in the regions. Cervical cancer preventive services were not available in these countries before the establishment of these projects. Thus, these programs now serve as a platform for screening and treatment. IARC and INCTR will work together to ensure that the research objectives are also successfully addressed and that the projects are sustained and expanded to provide wider services and training opportunities in these countries and regions in the future.

R. Sankaranarayanan
International Agency for Research on Cancer (IARC), Lyon, France