Human papillomavirus infection among Egyptian females with cervical carcinoma: relationship to spontaneous apoptosis and TNF-alpha

Objectives: This study was designed to detect HPV type-16 in Cervical carci noma (CC) tissue specimens. The results were correlated with clinicopatholo gical parameters of the carcinoma, with spontaneous apoptosis and with immu noreactivity to TNF-alpha antibodies Methods: Fresh frozen tissue specimens representing 30 cases of cervical ca rcinoma as well as 20 normal cervical tissues (NCT) were the subjects of th is study. HPV-16 DNA was detected by Polymerase Chain Reaction (PCR). The o ccurrence of spontaneous apoptotic cell death was analyzed by the apoptosis assay. Apoptotic cells were also counted by Light microscopy and the apopt otic index (Al) was calculated. Electron microscopy was used to confirm the morphology of apoptotic cells. TNF-alpha was quantified using EIA kit. Results: HPV-16 DNA was more frequent in CC than in NCT. No correlation was observed between HPV infection and grade, stage or pathologic type of CC. The occurrence of spontaneous apoptosis was significantly higher in CC than in NCT, where it was correlated to advanced tumor stage and tumor patholog y being more in adenocarcinoma (AC) than in squamous cell carcinoma (SCC). Moreover, Al was negatively correlated to HPV-16 infection. TNF-alpha level s were significantly higher in CC vs. NCT, where they were positively corre lated to advanced tumor stage. TNF-alpha levels were correlated to DNA frag mentation and Al (r = 0.47 and 0.57 respectively). A cut-off value for TNF- alpha was calculated to be 9.1 pg/mg protein (using ROC curve). At the dete rmined cut-off point the sensitivity was 70% and the specificity was 80%. Conclusion: HPV infection, high levels of TNF-alpha and spontaneous apoptos is were strongly associated with malignant phenotype of cervical tissues. R ate of spontaneous apoptosis was higher in AC compared to SCC. On the other hand, HPV negativity was correlated with Al. Moreover, TNF-alpha and apopt otic cell death were correlated to each other as well as to tumor progressi on. No correlation was detected between TNF-alpha and HPV-16 infection. (C) 2001 The Canadian Society of Clinical Chemists. All rights reserved.