P16INK4A and MIB-1 Expression in Preneoplasia and Neoplasia of Cervix

Cervical cancer is the third most common cancer and fourth most common cause of cancer related deaths in female population, accounting to approximately 453,300 cases per year and 275,100 deaths in the year 2008. According to the latest WHO global cancer statistics, the cumulative risk (%) (Age 0-74) of cervical carcinoma is 0.9 with age adjusted ratio of 9.0 (Jemal et al., 2011). In India, cervical cancer is the leading cancer among females between 15 and 44 years of age. Current estimates indicate that every year 132,082 women are diagnosed with cervical cancer and that 74,118 die from this disease in India alone (http://www.who.int/hpv). Having said this, however, no form of cancer better documents the remarkable effects of prevention, early diagnosis, and curative therapy on the mortality rate than the cancer of cervix. However, the still very high rate of cervical carcinoma in developing countries like India is because of lack of proper screening methods and lack of health infrastructure which allows for periodical and routine screening. Potential threat of cancer has reduced significantly in developed countries, due to Papanicolaou smear screening programs. Papanicolaou smears or commonly referred as Pap smears is a cost effective and reproducible screening technique for diagnosing precursor lesions of cervical carcinoma. However, Pap test gives significant false positive (30%) (Sherman et al., 1994) and false negative (15-50%) results due to subjective test criteria (Arbyn et al., 2008). Apart from the Pap smear screening test, histopathological diagnosis of cervical intraepithelial neoplasias (CINs) and cervical carcinoma is considered as the age old “gold standard” method of diagnosis of cervical neoplasms. However this can also be biased by interobserver variability as reported before (Stoler & Schiffman, 2001). These factors limit, present screening programs and histopathological examination and emphasizes the need for the identification of specific biomarkers for dysplastic epithelial cells to aid in primary screening and lesion diagnosis.