Cervical cancer: screening and prevention.

Cancer of the cervix is the second most common life-threatening cancer among women worldwide and both incidence and mortality rates are likely to be underestimated in developing countries. HPV high risk strains play at least the major if not an absolutely necessary role in the etiology. The concept of cervical intraepithelial neoplasia (CIN) was introduced in 1968 as an equivalent to the term dysplasia, which means abnormal maturation. Cervical cancer progresses slowly from preinvasive CIN to invasive cancer and therefore screening for dysplasia is an important public health effort worldwide, given the accessibility of the primary organ site, the acceptability of current screening methods, and the long preinvasive period in which to detect disease and successfully intervene. It is widely accepted that detection and treatment of HPV-related dysplastic epithelial change in the form of CIN-2 and CIN-3 can prevent the development of invasive cervical cancer in individual patients. The mainstay of screening programs has been the Pap smear, introduced originally by George Papanicolaou in 1941. However, considerable numbers of false-negative Pap smears may occur with the traditional Pap technique, mostly due to sampling error. More recently, the use of liquid-based technologies such as ThinPrep and AutoCyte Prep have gained popularity, in part because of evidence suggesting reduction in the incidence of inadequate smears. It is also hoped that the ability to identify patients with oncogenic HPV types will lead to improved detection in women more likely to have squamous intraepithelial lesions. Hybrid Capture 2 is the latest refinement of HPV tests and has been described as having enhanced sensitivity. HPV DNA testing can be used as an adjunct to cytology in routine cervical disease screening programs. Establishment of the link between HPV and cervical cancer has further provided the impetus for research into prophylactic vaccination against the most common HPV types associated with the disease, HPV 16 and 18. Initial studies have provided evidence that L1 virus-like particle vaccines against HPV types (as monovalent, bivalent, or quadrivalent vaccines) prevent at least 90% of incident and persistent infections and their associated precursors of cervical cancer. This vaccine has sustained long-term vaccine efficacy against incident and persistent infections and in the long term should provide an answer to the cervical cancer problem. For the vast majority of women who have already been infected, however, continued screening and resection need to be emphasized.