Abstract
Cervical cancer is the fourth most common malignancy in women worldwide and a leading cause of cancer-related mortality in developing countries. Important etiological factors in this cancer are high-risk human papillomaviruses (HPV), as roughly 96% of cervical cancer cases are positive for these oncoviruses. On the other hand, it has been recently pointed out that E6/E7 oncoproteins of high-risk HPV can upregulate the programmed cell death-1/programmed cell death-ligand 1 (PD-1/PD-L1) axis. Likewise, several recent reports showed that checkpoint blockades targeting PD-1/PD-L1 pathways have achieved efficient clinical responses via suppressing cancer progression and improving survival in several types of human cancers including metastatic cervical cancer. In this review, we summarize recent advances in our understanding of the PD-1/PD-L1 signaling pathway and its interaction with high-risk HPV and their oncoproteins, which could have an important impact on the management of HPV-associated cancers including cervical.
Highlights
The World Health Organization (WHO) categorizes cervical cancer as the fourth most common cancer in females, accounting for 30% of cancer-mortality cases [1]
This review aims to underline the interrelation between high-risk human papillomavirus (HPV) oncoproteins and Programmed cell death-1 (PD-1)/PD-L1 in the pathogenesis of cervical cancer, which could reinforce the role of PD-1/PD-L1 inhibitors as one of the main therapies for the management of HPV-positive human carcinomas including cervical
It is known that the majority of human cervical cancers are positive for high-risk HPVs that involve three known oncoproteins, E5, E6, and E7, which regulate cell-cycle and tumor-suppressor genes, thereby affecting apoptosis and cell death program
Summary
The World Health Organization (WHO) categorizes cervical cancer as the fourth most common cancer in females, accounting for 30% of cancer-mortality cases [1]. In developing countries, cervical cancer is classified as the most frequent gynecological cancer [2]. The noted increase in disease prevalence in developing countries is partially attributed to immunecompromising conditions including HIV, which in turn is associated with a higher risk of persistent and multiple human papillomavirus (HPV) infections [3, 4]. On the basis of oncogenicity, HPVs are classified into high-risk [16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 69, 82] and low-risk [6, 8, 11, 40, 42, 43, 44, 54, 61, 72] [5], of which high-risk HPV types 16 and 18 are the most widespread carcinogenic strains to humans. Results from case–control studies report a convincing association between high-risk HPV types 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 66
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