Cervical cancer prevention strategies in the developing world

Cervical cancer accounts for an estimated 500 000 new cases and around 300 000 deaths annually in the world. Low‐ and medium‐resourced countries in Latin America, Sub‐Saharan Africa and South and South‐East Asia continue to account for four fifths of the global burden of cervical cancer. It is well established that cervical cancer is caused by persistent infection with one or more of the 15 oncogentic types of human papilloma viruses (HPV) and effective screening programmes to detect and treat cervical pre‐cancerous lesions can prevent cervical cancer. The high burden of cervical cancer in low‐ and medium resourced countries seems to be due to the lack of effective screening programmes and high prevalence (> 10% women aged 30–60 years) of infection with high‐risk oncogenic HPV types. The knowledge that cervical cancer is a rare long‐term outcome of a common, sexually transmitted viral infection has led to the exciting possibility of controlling cervical cancer by vaccination. HPV vaccines consist of virus‐like particles (VLPs), produced by recombinant technology and are administered as three 0.5 ml intramuscular injections over a six month period. Recent results from randomized trials indicate that HPV vaccines have an excellent safety profile, are highly immunogenic inducing high levels of serum antibodies in virtually all vaccinated individuals, and have conferred a high degree of protection around 99% against HPV‐16/18 infection and associated pre‐cancerous cervical lesions in fully vaccinated women. A quadrivalent vaccine targeting HPV types 6, 11, 16 and 18 has already been licensed and marketed in several countries and another bivalent vaccine targeting HPV types 16 and 18 is currently being evaluated and is widely expected to be soon licensed for clinical use in the near future. Although the duration of protection is not yet known, there is evidence of protection for at least five years after vaccination, and large studies are ongoing in Nordic countries to evaluate the longer‐term duration. While the vaccine seems to be promising, the vaccine costs are currently so high that it is unaffordable as of now for public health use or for target populations in developing countries. Delivery costs are also important, since in many settings new systems will be needed to reach young adolescents. Although there are several challenges before widespread vaccine use becomes a reality, this is an important development in the primary prevention of cervical cancer. Cervical screening is the most widely practiced approach to prevent invasive cervical cancer by detecting and treating women with high‐grade cervical intraepithelial neoplasia (CIN 2 and 3 lesions). The effectiveness of screening is evaluated by the extent of reduction in cervical cancer incidence and mortality following screening. Cervical screening tests such as cytology, visual and HPV tests are capable of identifying women having CIN as well as early, pre‐clinical invasive cancer. The critical components of successful cervical screening are high coverage of target women with accurate, quality assured screening tests and of screen‐positive women with diagnostic investigations, of women with confirmed cervical neoplasia with treatment and follow‐up care. For successful screening in low‐ resource countries, screening, diagnosis and treatment need to be provided on‐site ensuring wide coverage, and one needs a low‐cost, low technology tests that can provide immediate results and lead to immediate treatment. Currently, pre‐cancerous lesions are rarely diagnosed and treated and invasive cancers generally present at advanced stages with poor survival in most high‐risk developing countries. Cytology screening in developed countries has reduced the burden of cervical cancer. However, cytology requires complex inputs in sample collection, processing, reading and reporting of smears and quality assurance inputs for assured success. Cytology screening in developing countries in South and Central America, over the last three decades has achieved only limited success in preventing cervical cancer. The challenges and difficulties in implementing cytology screening in developing countries have stimulated the search for alternative methods of screening such as visual screening methods and HPV testing. The findings from studies addressing the accuracy of cytology and its alternatives such as visual inspection with acetic acid (VIA), visual inspection with Lugol's iodine (VILI) and HPV DNA testing in detecting cervical cancer and its precursors will be discussed in the context of evolving public health policy on introducing new and effective programmes in low‐resource settings and in re‐organizing existing programmes. The sensitivity of VIA and VILI seem to be similar to that of good quality cytology in studies in developing countries, while HPV testing seems to have a higher sensitivity. Interim findings from randomized trials evaluating visual and HPV tests for their effectiveness in reducing the risk of CIN and reducing incidence of and mortality from cervical cancer will be described. There are currently efforts to develop simple, easy to perform, rapid and affordable HPV tests. The large body of research findings and managerial guidelines as well as recent cost‐effectiveness data for different screening approaches in preventing cervical cancer should be taken into account while reorganizing existing inefficient screening programmes and when considering new initiatives in low‐ and medium‐resource settings.