CANCER OF THE UTERINE CERVIX - INTEGRATION OF MOLECULAR EVALUATION INTO MANAGEMENT STRATEGY AND THE CONCEPT OF BIOLOGICAL STAGING

Carcinoma of the uterine cervix is the most common malignancy affectin g Indian women. The biological behaviour of invasive cervical cancer i s not always predictable. Even when the lesion is localized to the cer vix, 15-20% of the patients have recurrences. The evaluation of cervic al precancer is even more complex and the current approach is to asses s malignant potential based on histological and cytological criteria. However, lesions at any point in the spectrum of premalignancy have be en associated with subsequent invasion, reflecting the limitations of histological grading for predicting the risk of progression. Biologica l markers are measures of cellular events associated with specific sta ges of carcinogenesis. This definition indicates that the risk of tumo ur progression and/or biological behaviour could correlate with the qu antitative degree and pattern of biomarker expression. A number of suc h markers are now available for the evaluation of cervical lesions. Mo lecular, biological and histopathological investigations of preinvasiv e and invasive carcinoma of the uterine cervix have shown the role of human papillomavirus (HPV) infection in cervical carcinogenesis. Molec ular analysis of HPV DNAs has also provided information on their genom ic organization, protein function and transcriptional regulation. Stud ies on the expression of E6 and E7 transforming proteins of certain hi gh-risk HPVs have shown that these viruses play a role in carcinogenic progression by forming complexes with products of the tumor suppresso r genes, Rb and p53. Studies have also shown the association of the on cogenes, ras and myc with HPV and cervical carcinoma. The role of HPV infection, E6-E7 transforming proteins, oncogenes and tumour suppresso r genes in cervical carcinogenesis are discussed in this paper. Evalua tion of these molecular markers can thus be used to elaborate the exis ting grading system for cervical lesions and could play a vital role i n the management of cervical precancer and cancer.