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Herpesviruses in the oral cavity of patients subjected to allogeneic hematopoietic stem cell transplantation and its relationship with oral mucositis

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Abstract

Objectives

This study was performed to characterise oral shedding of herpesviruses in patients who underwent allogeneic hematopoietic stem cell transplantation (alloHSCT) and to investigate its relationship with oral mucositis (OM).

Materials and Methods

PCR and enzymatic digestion were conducted to identify oral shedding of herpesviruses and its correlation with OM development in 31 patients. The samples were collected at three sites in the oral cavity and at 5 times during follow-up; two additional collections were made from patients who developed ulcerative OM.

Results

HSV-1, EBV, CMV, HHV-6A, HHV-6B, and HHV-7 were detected in 4.97%, 16.02%, 4.41%, 2.20%, 3.31%, and 68% of the oral mucosal samples, respectively; 4.41%, 16.57%, 5.52%, 2.20%, 5.52%, and 63.53% of supragingival samples, respectively, and 4.41%, 18.23%, 2.76%, 1.65%, 2.75%, and 35.91% of subgingival samples, respectively. OM was diagnosed in 13 patients. The presence of HHV-7 in C1 (oral mucosa: p = 0.032) and C2 (supragingival: p = 0.009; subgingival: p = 0.002) was significantly increased in patients who developed OM, and patients exhibiting HHV-7 shedding in the oral cavity were 3.32-fold more likely to develop OM.

Conclusions

Patients who developed OM showed higher HHV-7 shedding in the oral cavity at nadir (immediately prior to OM development), suggesting modifications to the inflammatory microenvironment.

Clinical Relevance

HHV-7 may be involved in oral dysbiosis in HSCT-related OM; enhanced understanding of its role in the pathogenesis of OM may lead to the development of strategies for managing and preventing this common side effect of alloHSCT.

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Abbreviations

alloHSCT:

allogenic hematopoietic stem cell transplantation

CMV:

Cytomegalovirus

EBV:

Epstein-Barr virus

HHV-6:

Human herpesvirus 6

HHV-7:

Human herpesvirus 7

HHV-8:

Human herpesvirus 8

HSV-1:

Herpes simplex virus 1

HSV-2:

Herpes simplex virus 2

OM:

Oral mucositis

RIC:

Reduced-intensity conditioning

VZV:

Varicella Zoster virus

WHO:

World Health Organization

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Funding sources

This study was supported by grants from Sao Paulo Research Foundation – FAPESP, Sao Paulo, Brazil [grant number 2015/07727–9], National Council for Scientific and Technology Development (CNPq) [grant number 443004/2014–5], and Coordination for the Improvement of Higher Education Personnel (CAPES).

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Authors and Affiliations

  1. Department of Oral Medicine, Hospital Sírio Libanês, Rua Dona Adma Jafet, 91-Bela Vista, São Paulo, SP, Brazil

    Wanessa Miranda-Silva & Eduardo Rodrigues Fregnani

  2. Sociedade Beneficente de Senhoras Hospital Sírio Libanês, São Paulo, Brazil

    Franciele Hinterholz Knebel & Anamaria Aranha Camargo

  3. Laboratory of Virology, Institute of Tropical Medicine of São Paulo, University of São Paulo, São Paulo, Brazil

    Tania Regina Tozetto-Mendozo & Paulo Henrique Braz-Silva

  4. Department of Stomatology, School of Dentistry, University of São Paulo, São Paulo, Brazil

    Michelle Palmieri & Paulo Henrique Braz-Silva

  5. Department of Oral Surgery and Pathology, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil

    Felipe Paiva da Fonseca

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  1. Wanessa Miranda-Silva
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  2. Franciele Hinterholz Knebel
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  3. Tania Regina Tozetto-Mendozo
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  6. Anamaria Aranha Camargo
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  7. Paulo Henrique Braz-Silva
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Correspondence to Eduardo Rodrigues Fregnani.

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This study was approved by the local ethics committee (N° 1.414.217) and conducted in accordance with the Declaration of Helsinki.

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Miranda-Silva, W., Knebel, F.H., Tozetto-Mendozo, T.R. et al. Herpesviruses in the oral cavity of patients subjected to allogeneic hematopoietic stem cell transplantation and its relationship with oral mucositis. Clin Oral Invest 24, 3597–3608 (2020). https://doi.org/10.1007/s00784-020-03234-3

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