Cytomegalovirus and systemic inflammation at time of surgery is associated with worse outcomes in serous ovarian cancer

Erin Wesley, Locke D. Uppendahl, Martin Felices, Carly Dahl, Audrey Messelt, Kristin L.M. Boylan, Amy P.N. Skubitz, Rachel I. Vogel, Heather H. Nelson, Melissa A. Geller

Research output: Contribution to journalArticlepeer-review

Abstract

Objectives: Cytomegalovirus (CMV) is a common infection that establishes latency in healthy people. CMV has been associated with alterations of the immune compartment leading to improved responses, while inflammation has been shown to adversely impact outcomes. We investigated whether CMV serostatus predicts outcomes in ovarian cancer in the presence or absence of inflammation. Methods: A total of 106 patients with serous ovarian cancer from 2006 to 2009 were analyzed. CMV and systemic inflammation was measured using CMV immunoglobulin G (IgG) and C-reactive protein (CRP), respectively, in serum collected prior to cytoreduction. Patients were stratified by CMV IgG (non-reactive, reactive/borderline) and CRP (≤10, >10 mg/L) status. Overall survival (OS) and recurrence-free survival (RFS) were compared by group using log-rank tests and Cox proportional hazards regression models adjusting for age at surgery. Results: Of 106 eligible patients, 40 (37.7%) were CMV+/CRP+, 24 (22.6%) CMV+/CRP-, 19 (17.9%) CMV−/CRP+, and 23 (21.7%) CMV−/CRP−. CRP+ had higher CA-125 levels (P = 0.05) and higher rates of suboptimal debulking (P = 0.03). There were no other significant differences in demographic, surgical, or pathologic factors between groups. CMV+/CRP+ patients median RFS and OS were 16.9 months (95% CI: 9.0–21.1) and 31.7 months (95% CI: 25.0–48.7), respectively, with a significantly worse RFS (aHR: 1.85, 95% CI: 1.05–3.24, P = 0.03) and OS (aHR: 2.12, 95% CI: 1.17–3.82, P = 0.01) compared to CMV−/CRP− (RFS = 31.2 months (95% CI: 16.0–56.4) and OS = 63.8 months (95% CI: 50.7–87.0)). CMV+/CRP− group displayed the longest OS (89.3 months). Conclusions: Previous exposure to CMV and high CRP at surgery portended worse RFS and OS compared to women who tested negative. The CMV+/CRP− group had the longest OS, indicating that CMV status alone, in the absence of inflammation, may be protective.

Original languageEnglish (US)
Pages (from-to)193-198
Number of pages6
JournalGynecologic oncology
Volume160
Issue number1
DOIs
StatePublished - Jan 2021

Bibliographical note

Funding Information:
Department of Defense Ovarian Cancer Research Program Ovarian Cancer Academy Early Career Investigator Award (OC180392); USA, Hematology Research Training Program T32 (2T32HL007062); USA, American Cancer Society Research Scholar Grant (RSG-14-151-01-CCE); USA, Mary Belle Soener Research University of Minnesota Foundation Grant, USA.

Funding Information:
Department of Defense Ovarian Cancer Research Program Ovarian Cancer Academy Early Career Investigator Award ( OC180392); USA , Hematology Research Training Program T32 ( 2T32HL007062 ); USA, American Cancer Society Research Scholar Grant ( RSG-14-151-01-CCE ); USA, Mary Belle Soener Research University of Minnesota Foundation Grant, USA.

Publisher Copyright:
© 2020 Elsevier Inc.

Keywords

  • CMV
  • Cytomegalovirus
  • Inflammation
  • Ovarian cancer
  • c-Reactive protein

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, Non-U.S. Gov't

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