Prospects on Prevention and Early Detection of Cervical Cancer in Developing Countries
R. Sankaranarayanan MD, Head, Screening Group, International Agency for Research on Cancer, Lyon, France



Low- and medium-resource countries in Latin America, Sub-Saharan Africa and South and South-East Asia account for more than 80% of the world burden of cervical cancer. Cervical cancer remains largely uncontrolled in these countries due to lack of or inefficient screening programmes and high prevalence of oncogenic HPV infections. While early detection of occult, asymptomatic precancerous lesions by screening and their effective treatment lead to the prevention of invasive cervical cancer and premature death, the fact that cervical cancer is caused by persistent oncogenic HPV infection provides the exciting opportunity for prevention through vaccination.

Primary prevention through HPV vaccination offers a new tool to improve cervical cancer control. Currently available HPV vaccines target HPV 16 and 18. Monovalent (HPV 16), bivalent (HPV 16 and 18) and quadrivalent (HPV 6,11,16 and 18) virus-like particle (VLP) vaccines have been evaluated in randomized Phase II and III trials. The results from these trials indicate, with remarkable consistency, that a regimen of three intramuscular injections of HPV L1 (VLP) vaccine offers HPV–naive women a very high-level of protection from infections and cervical intraepithelial neoplasia (CIN) associated with the HPV types included in the vaccine, and are well tolerated and safe, indicating their vast potential to reduce HPV related morbidity and mortality, if offered to girls before onset of sexual activity. However, widespread implementation of HPV vaccines is fraught with several challenges and uncertainties that include the current prohibitively high costs, socio-cultural barriers, logistical difficulties in vaccinating early adolescent or preadolescent girls, vaccine delivery costs, cold chain capacity (refrigeration during distribution) and information needs. Additional information is urgently required on issues such as cross-protection against other HPV genotypes, safety of administration with other vaccines, cost of vaccine over time, innovative dosage delivery schemes (e.g., the use of two doses or even a single dose) in order to realize the actual implementation of this new method in a public health settings.

Currently, precancerous lesions are rarely diagnosed and treated in developing countries and invasive cancers present at advanced stages, resulting in low cure rates. Cytology screening has been mainly responsible for the significant decrease in the burden of cervical cancer in developed countries. However, cytology requires complex inputs in sample collection, processing, and the reading and reporting of smears. Although Pap smear screening has been introduced over the last three decades in some developing countries, particularly in Latin America, this has had little or no impact on the burden of cervical cancer. The findings from studies addressing the accuracy of Pap smear and its potential alternatives, such as visual inspection with acetic acid (VIA) or Lugol's iodine (VILI) and HPV DNA testing in detecting CIN, indicate that they are useful early detection tests. The accuracy of VIA and VILI seems to be similar to that of good quality cytology in the most recent studies in low-resource countries. The efficacy of VIA- or HPV testing followed by immediate treatment with cryotherapy has been evaluated in single-visit "screen-and-treat" programs for reduction in the prevalence CIN in South Africa. The results from this study indicate that both screen-and-treat approaches are safe and result in a lower prevalence of CIN compared with delayed evaluation at both 6 and 12 months.

The efficacy and cost-effectiveness of new paradigms in cervical screening such as a single life-time screening with VIA, cytology or HPV testing in preventing invasive cervical cancer are being evaluated in randomised controlled trials. In a randomized trial in India, a 25% reduction in cervical cancer incidence and 35% reduction in mortality has been reported following a single round of VIA screening. In another trial in India evaluating the comparative efficacy of a single round of VIA screening, cytology or HPV testing, the detection rate of high-grade lesions was similar: 0.7% for VIA, 1.0% for cytology and 0.9% for HPV testing. The large body of research findings and managerial guidelines, as well as emerging data from on-going studies on the cost-effectiveness of different screening approaches in preventing cervical cancer, need to be taken into account when reorganizing existing inefficient screening programmes and when considering new programmes in low- and medium-resource countries. While HPV vaccination provides the hope for the future, screening provides the current means of cervical cancer prevention.