Friend or Foe? Exploring the Role of Cytomegalovirus (HCMV) Infection in Head and Neck Tumors

Author:

Trivic Aleksandar12,Milovanovic Jovica12,Kablar Djurdjina3,Tomic Ana4ORCID,Folic Miljan12ORCID,Jotic Ana12ORCID,Tomanovic Nada25,Tomic Ana Marija25,Djoric Igor26,Jankovic Marko27ORCID

Affiliation:

1. Clinic for Otorhinolaryngology and Maxillofacial Surgery, University Clinical Center of Serbia, 2 Pasterova Street, 11000 Belgrade, Serbia

2. Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia

3. Department for Pathology, Pathohistology and Medical Cytology, University Clinical Centre of Serbia, 11000 Belgrade, Serbia

4. Center for Radiology Imaging, University Clinical Center of Serbia, 2 Pasterova Street, 11000 Belgrade, Serbia

5. Institute of Pathology, 1 Dr. Subotica Street, 11000 Belgrade, Serbia

6. Clinic of Neurosurgery, University Clinical Center of Serbia, Institute of Radiology, 4 Dr. Koste Todorovića Street, 11000 Belgrade, Serbia

7. Department of Virology, Institute of Microbiology and Immunology, 1 Dr. Subotica Street, 11000 Belgrade, Serbia

Abstract

Although not regarded as an oncogenic pathogen, the human cytomegalovirus (HCMV) has been associated with a wide array of malignancies. Conversely, a number of studies report on possible anti-tumor properties of the virus, apparently mediated via HCMV-galvanized T-cell tumor killing; these were recently being investigated in clinical trials for the purposes of anti-cancer treatment by means of dendritic cell vaccines and HCMV-specific cytotoxic T cells. In the present study, we have analyzed the relation between a complement of head-and-neck tumors and HCMV infection across 73 countries worldwide using Spearman correlation, univariate and multivariate regression analysis. Intriguingly, HCMV was found to be pro-oncogenic in patients with nasopharyngeal carcinoma; contrarywise, the virus manifested an inverse (i.e., anti-tumor) association with the tumors of the lip/oral region and the salivary glands. Although this putative protective effect was noted initially for thyroid neoplasia and hypopharyngeal tumors as well, after multivariate regression analysis the connection did not hold. There was no association between laryngeal cancer and HCMV infection. It would appear that, depending on the tissue, HCMV may exert both protective and oncogenic effects. The globally observed protective feature of the virus could potentially be utilized in future therapeutic approaches for salivary tumors and neoplasia in the lip/oral region. As correlation does not necessarily imply causation, more in-depth molecular analyses from comprehensive clinical studies are warranted to substantiate our findings.

Funder

Ministry of Science, Technological Development and Innovation (MSTDI) of the Republic of Serbia

Publisher

MDPI AG

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