Overview of Human Papillomavirus-Based and Other Novel Options for Cervical Cancer Screening in Developed and Developing Countries

Screening for cervical cancer precursors by cytology has been very successful in countries where adequate resources exist to ensure high quality and good coverage of the population at risk. Mortality reductions in excess of 50% have been achieved in many developed countries; however the procedure is generally inefficient and unworkable in many parts of the world where the appropriate infrastructure is not achievable. A summary and update of recently published meta-analyses and systematic reviews on four possible clinical applications of human papillomavirus (HPV) DNA testing is provided in this article: (1) triage of women with equivocal or low-grade cytological abnormalities; (2) follow-up of women with abnormal screening results who are negative at colposcopy/biopsy; (3) prediction of the therapeutic outcome after treatment of cervical intraepithelial neoplasia (CIN), and most importantly (4) primary screening HPV DNA test, solely or in combination with Pap smear to detect cervical cancer precursors. There are clear benefits for the use of HPV DNA testing in the triage of equivocal smears, low-grade smears in older women and in the post-treatment surveillance of women after treatment for CIN. However, there are still issues regarding how best to use HPV DNA testing in primary screening. Primary screening with Hybrid Capture((R)) 2 (HC2) generally detects more than 90% of all CIN2, CIN3 or cancer cases, and is 25% (95% CI): 15-36%) relatively more sensitive than cytology at a cut-off of abnormal squamous cells of undetermined significance (ASC-US) (or low-grade squamous intraepithelial lesions (LSIL) if ASC-US unavailable), but is 6% (95% CI: 4-7%) relatively less specific. Several approaches are currently under evaluation to deal with the lower specificity of HPV DNA testing as associated with transient infection. These include HPV typing for HPV-16 and -18/45, markers of proliferative lesions such as p16 and mRNA coding for the viral E6 and/or E7 proteins, with a potential clinical use recommending more aggressive management in those who are positive. In countries where cytology is of good quality, the most attractive option for primary screening is to use HPV DNA testing as the sole screening modality with cytology reserved for triage of HPV-positive women. Established cytology-based programmes should also be gradually moving towards a greater use of HPV DNA testing to improve their efficacy and safely lengthen the screening interval. The greater sensitivity of HPV DNA testing compared to cytology argues strongly for using HPV DNA testing as the primary screening test in newly implemented programmes, except where resources are extremely limited and only programmes based on visual inspection are affordable. In such countries, use of a simple HPV DNA test followed by immediate 'screen and treat' algorithms based on visual inspection in those who are HPV-positive are needed to minimise the number of visits and make best use of limited resources. A review of studies for visual inspection methods is presented. The fact that HPV is a sexually transmitted infection may lead to anxiety and concerns about sexual relationships. These psychosocial aspects and the need for more information and educational programmes about HPV are also discussed in this article.