Strong association between herpes simplex virus-1 and chemotherapy-induced oral mucositis in patients with hematologic malignancies

Abstract

Background/Aims: A link between oral cavity infections and chemotherapy-induced oral mucositis (CIOM) in patients with hematological malignancies (HMs) undergoing intensive chemotherapy (IC) or hematopoietic stem cell transplantation (HSCT) has been suggested. However, conclusive data are lacking, and there are no current guidelines for the prophylactic use of antimicrobials to prevent CIOM in these populations. Methods: The relationships between herpes simplex virus (HSV) reactivation and Candida colonization in the oral cavity and CIOM in patients with HMs undergoing IC or HSCT were evaluated. Patients aged ≥ 19 years with HMs undergoing IC or HSCT were enrolled. Each patient was evaluated for HSV and Candida in the oral cavity along with CIOM at baseline and during the 2nd, 3rd, and 4th weeks. Results: Seventy presentations among 56 patients were analyzed. CIOM was observed in 23 presentations (32.9%), with a higher incidence associated with HSCT (17 of 35 presentations, 48.6%) than with IC (six of 35 presentations, 8.6%). The reactivation of HSV-1 was significantly associated with an increased incidence of CIOM after adjusting for age, sex, type of disease, and treatment stage. A higher HSV-1 viral load was associated with an increased incidence of CIOM. The presence of Candida was not associated with CIOM. Conclusions: HSV-1 reactivation in the oral cavity was highly associated with CIOM in patients with HMs undergoing high-dose chemotherapy.

Association of HSV-1 and Reduced Oral Bacteriota Diversity with Chemotherapy-Induced Oral Mucositis in Patients Undergoing Autologous Hematopoietic Stem Cell Transplantation

“…The exclusion criteria were as follows: (1) any prior radiation therapy or surgery within the 3 weeks prior to enrollment; (2) patients with definitive symptoms or signs of OM at baseline; (3) those with other severe dental diseases or systemic diseases that could significantly affect the study outcomes, including active infection, uncontrolled diabetes, and symptomatic cardio-or cerebrovascular disorders; (4) smokers; and (5) those who had underlying psychological diseases or cognitive disorders that precluded necessary communication. Twenty-two patients were included in our previous study [2]. For the control group, the inclusion criterion was age ≥ 19 years, and the exclusion criteria were as follows: (1) smokers; (2) the use of antibiotics or steroid within the last month; (3) any medication for systemic diseases; and (4) subjects with any lesions in the oral mucosa.…”

“…For the control group, the inclusion criterion was age ≥ 19 years, and the exclusion criteria were as follows: (1) smokers; (2) the use of antibiotics or steroid within the last month; (3) any medication for systemic diseases; and (4) subjects with any lesions in the oral mucosa. Sample size was estimated base on the prevalence of OM and the structure of mucosal bacteriota in previous studies [2,11]. All of the enrolled patients received a basic dental examination that included panoramic radiography and visual examination for the presence of potential foci of infection, oral mucosal diseases, and any abnormal changes in the oral mucosa.…”

“…Genomic DNA was extracted from the membrane using the DNeasy ® Power soil kit (Qiagen, Hilden, Germany) and eluded in 100 µL water. The presence of the HSV genome in the oral mucosa was determined by PCR using the isolated DNA and the HSV 1/2 PCR kit (BioCore, Seoul, South Korea) as previously described [2].…”

“…We previously reported that OM has a strong association with HSV-1 but no association with Candida, plaque index, or decayed, missing, and filled surface (DMFS) scores in patients with hematological malignancies undergoing intensive chemotherapy or HSCT [2]. However, only 46% of patients with positive HSV-1 detection developed OM, suggesting the role of additional factors.…”

“…Patients who receive a concomitant radiation therapy in the head and neck area, intensive chemotherapy for acute leukemia, or myeloablative conditioning for hematopoietic stem cell transplantation (HSCT) are at particularly high risk for OM [1]. The prevalence of OM in HSCT patients has been reported to be 49-99% [2][3][4]. OM is associated with severe pain, increased use of opioid analgesics, dysphagia, interruption of planned chemotherapy, bloodstream infection, and increased medical costs [1].…”