title: Oral shedding of human herpesviruses in patients undergoing radiotherapy/chemotherapy treatment for head and neck squamous cell carcinoma.
abstract: OBJECTIVE
  Opportunistic infections may affect the oral mucosa of patients undergoing radio/chemotherapy through exacerbation of oral mucositis. The aim of this study is to evaluate the oral shedding of all eight human herpesviruses and its possible association with oral mucositis.
  
  
  METHODS
  In this prospective cohort study, we analyzed oral rinse samples, collected weekly, from 20 patients during radiotherapy treatment. Serologic status to HSV1 and HSV2, EBV, CMV, and VZV in three different periods was performed by ELISA assay. PCR and enzymatic digestion was performed to detect HSV1, HSV2, EBV, CMV, VZV, HHV6, HHV7, and HHV8. Oral mucositis was evaluated according to the WHO criteria.
  
  
  RESULTS
  Oral shedding of EBV, HHV6, and HHV7 was observed in all weeks of radiotherapy. Considering the episodes of shedding, the highest frequency was found in patients with EBV excretion (55.0%). No virus reactivation was observed by serological analysis. EBV oral shedding frequency was significantly higher than that of other viruses and showing a positive correlation with oral mucositis grade ≥2.
  
  
  CONCLUSIONS
  There was a positive correlation between EBV oral shedding and oral mucositis grade ≥2, particularly after 3 weeks of radiotherapy, a period in which the severity of mucositis was statistically higher. These findings allow us to infer that the local inflammatory environment in mucositis grade ≥2 is more favorable for EBV replication.
  
  
  CONCLUSIONS
  Mucositis is a frequent and important side effect of radio/chemotherapy treatment. Understanding the possible participation of viruses in the mechanism of this condition is important to develop strategies for treatment and prevention.
authors.affiliation: Division of Pathology, Department of Stomatology, School of Dentistry, University of São Paulo, Av. Prof. Lineu Prestes, 2227-Cidade Universitária, São Paulo, SP, 05508-000, Brazil.
authors.forename: Michelle
authors.initials: M
authors.lastname: Palmieri
authors.affiliation: Division of Pathology, Department of Stomatology, School of Dentistry, University of São Paulo, Av. Prof. Lineu Prestes, 2227-Cidade Universitária, São Paulo, SP, 05508-000, Brazil.
authors.forename: Victor Adriano de Oliveira
authors.initials: VAO
authors.lastname: Martins
authors.affiliation: Laboratory of Virology, Institute of Tropical Medicine, University of São Paulo, Av. Dr. Enéas de Carvalho Aguiar, 470-Jd. América, São Paulo, SP, 05403-000, Brazil.
authors.forename: Laura Masami
authors.initials: LM
authors.lastname: Sumita
authors.affiliation: Laboratory of Virology, Institute of Tropical Medicine, University of São Paulo, Av. Dr. Enéas de Carvalho Aguiar, 470-Jd. América, São Paulo, SP, 05403-000, Brazil.
authors.forename: Tania Regina
authors.initials: TR
authors.lastname: Tozetto-Mendoza
authors.affiliation: Division of Pathology, Department of Stomatology, School of Dentistry, University of São Paulo, Av. Prof. Lineu Prestes, 2227-Cidade Universitária, São Paulo, SP, 05508-000, Brazil.
authors.forename: Bruna Baraldi
authors.initials: BB
authors.lastname: Romano
authors.affiliation: Laboratory of Virology, Institute of Tropical Medicine, University of São Paulo, Av. Dr. Enéas de Carvalho Aguiar, 470-Jd. América, São Paulo, SP, 05403-000, Brazil.
authors.forename: Clarisse Martins
authors.initials: CM
authors.lastname: Machado
authors.affiliation: Laboratory of Virology, Institute of Tropical Medicine, University of São Paulo, Av. Dr. Enéas de Carvalho Aguiar, 470-Jd. América, São Paulo, SP, 05403-000, Brazil.
authors.forename: Claudio Sergio
authors.initials: CS
authors.lastname: Pannuti
authors.affiliation: Division of Dentistry, Instituto do Câncer do Estado de São Paulo Octávio Frias de Oliveira, Av. Dr. Arnaldo, 251-Cerqueira César, São Paulo, SP, 01246-000, Brazil.
authors.forename: Thaís Bianca
authors.initials: TB
authors.lastname: Brandão
authors.affiliation: Division of Dentistry, Instituto do Câncer do Estado de São Paulo Octávio Frias de Oliveira, Av. Dr. Arnaldo, 251-Cerqueira César, São Paulo, SP, 01246-000, Brazil.
authors.forename: Ana Carolina Prado
authors.initials: ACP
authors.lastname: Ribeiro
authors.affiliation: Division of Pathology, Department of Stomatology, School of Dentistry, University of São Paulo, Av. Prof. Lineu Prestes, 2227-Cidade Universitária, São Paulo, SP, 05508-000, Brazil.
authors.forename: Luciana
authors.initials: L
authors.lastname: Corrêa
authors.affiliation: Division of Pathology, Department of Stomatology, School of Dentistry, University of São Paulo, Av. Prof. Lineu Prestes, 2227-Cidade Universitária, São Paulo, SP, 05508-000, Brazil. pbraz@usp.br.|Laboratory of Virology, Institute of Tropical Medicine, University of São Paulo, Av. Dr. Enéas de Carvalho Aguiar, 470-Jd. América, São Paulo, SP, 05403-000, Brazil. pbraz@usp.br.
authors.forename: Paulo Henrique
authors.initials: PH
authors.lastname: Braz-Silva
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000532:radiotherapy*; D003131:Combined Modality Therapy; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D006564:Herpesviridae; D006801:Humans; D053685:Laser Therapy; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011446:Prospective Studies; D013280:Stomatitis / Q000145:classification / Q000517:prevention & control / Q000821:virology*; D017201:Virus Shedding
keywords: Human herpesviruses; Oral mucositis; Radiotherapy; Squamous cell carcinoma