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

Gynecol Oncol. 2021 Jan;160(1):193-198. doi: 10.1016/j.ygyno.2020.10.029. Epub 2020 Nov 7.

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.

Keywords: CMV; Cytomegalovirus; Inflammation; Ovarian cancer; c-Reactive protein.

Publication types

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

MeSH terms

  • Aged
  • C-Reactive Protein / metabolism
  • Cystadenocarcinoma, Serous / blood
  • Cystadenocarcinoma, Serous / pathology
  • Cystadenocarcinoma, Serous / surgery*
  • Cystadenocarcinoma, Serous / virology*
  • Cytomegalovirus / isolation & purification
  • Cytomegalovirus Infections / blood*
  • Cytomegalovirus Infections / pathology
  • Cytomegalovirus Infections / virology
  • Disease-Free Survival
  • Female
  • Humans
  • Inflammation / blood
  • Inflammation / pathology
  • Inflammation / virology*
  • Middle Aged
  • Ovarian Neoplasms / blood
  • Ovarian Neoplasms / pathology
  • Ovarian Neoplasms / surgery*
  • Ovarian Neoplasms / virology*
  • Survival Rate
  • Treatment Outcome

Substances

  • C-Reactive Protein