Inflammation induced by human papillomavirus in cervical cancer and its implication in prevention.
Many pathological conditions including most cancers show an exacerbated activation of the inflammatory pathways and their sustained maintenance. In cervical carcinogenesis, the hyperactivation of the inflammatory pathways plays an important role in tumorigenesis, progression of the disease from low-grade lesions to invasive cervical cancer as well as in the initiation of other infections such as HIV. Cyclooxygenase-2 (COX-2) is the inducible isoform of cyclooxygenases regulated by growth factors and cytokines, hence overexpressed under inflammatory conditions. Higher levels of COX-2 expression are closely related to a higher incidence of parametrial invasion and lymph node metastases in early-stage uterine cervical cancer. The principal products of COX-2 enzyme, prostanoids, are released from cells and act locally in autocrine and paracrine modes, activating diverse intracellular pathways, which in turn induce cellular proliferation, antiapoptotic activity, angiogenesis, and increased metastasis. In the current review, we focus on the role of the viral oncogenic proteins in activation of the COX-2/PGE2 pathway and their clinical implications, a better understanding of which would be helpful in designing newer and more effective therapeutic and preventive strategies for the disease.
School of Medical Science and Technology, Indian Institute of Technology, Kharagpur, West Bengal, India.
Sheetal
S
Parida
Mahitosh
M
Mandal
D005260:Female; D006801:Humans; D007249:Inflammation / Q000209:etiology* / Q000473:pathology; D027383:Papillomaviridae / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000150:complications* / Q000821:virology; D011379:Prognosis; D002583:Uterine Cervical Neoplasms / Q000209:etiology* / Q000473:pathology