Cytomegalovirus infection in malignant pleural mesothelioma

Our plain-English summary of Cytomegalovirus infection in malignant pleural mesothelioma, by D. Hunter-Schlichting, K.T. Kelsey, R. Demmer, et al (PloS One, 2021).

The study

• Authors: D. Hunter-Schlichting, K.T. Kelsey, R. Demmer, M. Patel, R. Bueno, B. Christensen, N. Fujioka, D. Kolarseri, H.H. Nelson
• Journal: PloS One
• Published: 2021;16(8):e0254136
• Cited by: 4 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Human cytomegalovirus (HCMV) is a highly prevalent herpes virus which persists as a latent infection and has been detected in several different tumor types. HCMV disease is rare but may occur in high-risk settings, often manifesting as a pulmonary infection. To date HCMV has not been investigated in malignant pleural mesothelioma (MPM). In a consecutive case series of 144 MPM patients we evaluated two biomarkers of HCMV: IgG serostatus (defined as positive and negative) and DNAemia (>100 copies/mL of cell free HCMV DNA in serum). Approximately half of the MPM patient population was HCMV IgG seropositive (51%). HCMV DNAemia was highly prevalent (79%) in MPM and independent of IgG serostatus. DNAemia levels consistent with high level current infection (>1000 copies/mL serum) were present in 41% of patients. Neither IgG serostatus nor DNAemia were associated with patient survival. In tissues, we observed that HCMV DNA was present in 48% of tumors (n = 40) and only 29% of normal pleural tissue obtained from individuals without malignancy (n = 21). Our results suggest nearly half of MPM patients have a high level current HCMV infection at the time of treatment and that pleural tissue may be a reservoir for latent HCMV infection. These findings warrant further investigation to determine the full spectrum of pulmonary infections in MPM patients, and whether treatment for high level current HCMV infection may improve patient outcomes.

In plain English

This study looked for human cytomegalovirus (HCMV), a common herpes virus, in 144 malignant pleural mesothelioma patients seen at the International Mesothelioma Program at Brigham and Women's Hospital between May 2000 and May 2005. Blood was tested for HCMV antibodies (IgG) and for viral DNA. Of the 144 patients, 113 (79%) had HCMV DNA in their blood, and 41% had levels above 1000 copies/mL, which the authors classed as a high-level current infection. IgG seroprevalence was 52% and was not associated with blood viral DNA. Age, sex, tumor histology and asbestos exposure were similar across the viral DNA groups. Among 22 metastatic lung cancer patients, none had levels above 1000 copies/mL. HCMV DNA was found in 19 of 40 tumors (48%) and in 6 of 21 normal pleural samples from people without cancer (29%; p = 0.47). None of the survival comparisons was statistically significant. The authors concluded that their data support the hypothesis that active HCMV infection is a common unrecognized event in mesothelioma patients that may be associated with poor survival. They noted limitations, including blood draws that were not timed consistently and missing treatment information.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Retrospective analysis of stored blood and tissue samples from patients in an earlier epidemiologic study of mesothelioma (described in the abstract as a consecutive case series), with comparison groups of normal pleural tissue and metastatic lung cancer patients
• Who was studied: 144 patients with malignant pleural mesothelioma enrolled at the International Mesothelioma Program, Brigham and Women's Hospital (Boston), May 2000 to May 2005. Tumor DNA was available for 40 of them. Comparison groups were 21 normal pleural samples from patients without mesothelioma, with no known asbestos exposure and no pleural disease, and 22 metastatic lung cancer patients from a University of Minnesota biobank (enrolled from March 2017).
• Exposure: The exposure studied was HCMV infection, measured as IgG serostatus and as HCMV DNA in serum (above 100 copies/mL counted as present, above 1000 copies/mL as high-level current infection), plus HCMV DNA in tumor and normal pleural tissue. Asbestos exposure history was collected by questionnaire and reported only as yes or no. No fiber types were named.
• Main results:
  • In the 144 mesothelioma patients, 113 (79%) had HCMV DNA in serum.
  • 41% of the mesothelioma patients had serum HCMV DNA levels above 1000 copies/mL.
  • HCMV IgG seroprevalence among the mesothelioma patients was 52%, and IgG status was not associated with the presence or level of serum HCMV DNA.
  • Age, sex, histology and asbestos exposure were similar across the serum HCMV DNA groups (p = 0.22 for asbestos exposure in Table 1).
  • In the comparison group of 22 metastatic lung cancer patients, the prevalence of serum HCMV DNA was reported as 80%, but none had levels above 1000 copies/mL.
  • HCMV DNA was found in 19 of 40 mesothelioma tumors (48%). Tumor HCMV status was not associated with serum HCMV DNA or IgG status.
  • HCMV DNA was found in 6 of 21 normal pleural samples from people without cancer (29%). The p-value printed for the comparison with tumors was 0.47.
  • Median survival of the mesothelioma patients was 17.2 months overall. It was 16.2 months with no serum HCMV DNA, 15.6 months with levels above 1000 copies/mL, and 21.1 months with low-level serum HCMV DNA.
  • After adjustment for age, gender and histology, survival did not differ from patients with no serum HCMV DNA, either for low-level DNA (HR 1.01, 95% CI 0.59–1.71) or for high-level DNA (HR 1.26, 95% CI 0.77–2.08).
  • IgG status was not associated with survival (HR 1.03, 95% CI 0.65–1.44), and HCMV in the tumor was not associated with survival.
  • The authors stated that none of the survival observations were statistically significant.
• The authors' conclusion: The authors concluded that their data support the hypothesis that active HCMV infection is a common unrecognized clinical event among mesothelioma patients that may be associated with poor patient survival. They said further study is warranted.
• Limitations the authors state:
  • Blood draws were not standardized in relation to the course of treatment, which the authors said makes the estimate of serum HCMV DNA prevalence unstable.
  • The study could not tell new infection from reactivation of a latent infection, and HCMV status may have been misclassified by either the DNA or the antibody test.
  • Only a small amount of tissue was tested, so tissue prevalence is likely an underestimate and tumor status may be misclassified.
  • Treatment information was not available.
  • Patient symptoms and co-infections were not assessed at the time of blood draw. IgM and bronchial samples were also not available.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Biomarker.

Related studies

• Seroprevalence of West Nile Virus specific IgG and IgM antibodies in North-Western and Western provinces of Zambia — I. Mweene-Ndumba, S. Siziya, et al. (2015)
• COVID-19 in patients with thoracic malignancies (TERAVOLT): first results of an international, registry-based, cohort study — M.C. Garassino, J.G. Whisenant, et al. (2020)
• High prevalence of serum antibodies reacting with simian virus 40 capsid protein mimotopes in patients affected by malignant pleural mesothelioma — E. Mazzoni, A. Corallini, et al. (2012)
• Treatment of primary and metastatic peritoneal tumors in the Covid-19 pandemic. Proposals for prioritization from the RENAPE and BIG-RENAPE groups — O. Glehen, V. Kepenekian, et al. (2020)
• Cancer in the time of COVID-19: expert opinion on how to adapt current practice — J. Raskin, M. Lebeer, et al. (2020)
• SV40 multiple tissue infection and asbestos exposure in a hyperendemic area for malignant mesothelioma — M. Comar, C. Rizzardi, et al. (2007)

Browse more research in PloS One, or return to medical research.