Oral shedding of human herpesviruses in patients undergoing radiotherapy/chemotherapy treatment for head and neck squamous cell carcinoma

Clin Oral Investig. 2017 Sep;21(7):2291-2301. doi: 10.1007/s00784-016-2022-x. Epub 2016 Dec 14.

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.

Materials and 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.

Clinical relevance: 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.

Keywords: Human herpesviruses; Oral mucositis; Radiotherapy; Squamous cell carcinoma.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / radiotherapy*
  • Combined Modality Therapy
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Head and Neck Neoplasms / drug therapy*
  • Head and Neck Neoplasms / radiotherapy*
  • Herpesviridae*
  • Humans
  • Laser Therapy
  • Male
  • Middle Aged
  • Polymerase Chain Reaction
  • Prospective Studies
  • Stomatitis / classification
  • Stomatitis / prevention & control
  • Stomatitis / virology*
  • Virus Shedding*