Researchers noted that it remains unclear whether cytomegalovirus (CMV) infection is a specific cause of worsened cancer-related cognitive impairment (CRCI), or if it is a biomarker for immune suppression.
Active cytomegalovirus (CMV) infection was found to be common among patients with ovarian cancer undergoing chemotherapy, and the infection may be contributing to symptoms of cancer-related cognitive impairment (CRCI), according to research published in BMC Cancer.
CRCI is a commonly reported effect of cancer and cancer treatments, and viral infections can impact inflammation and immune function that can potentially influence patient symptoms, including CRCI.
This study aimed to outline the occurrence of CMV infections at various stages—diagnosis, during, and after chemotherapy—in patients with ovarian cancer, and investigate the association between CMV infection at the time of diagnosis and the development of CRCI following chemotherapy.
To do so, researchers enrolled adults with recently diagnosed ovarian, primary peritoneal, or fallopian tube cancer into 2 prospective studies at a single academic cancer center.
In Study 1, which included 71 participants, blood samples were collected at the time of diagnosis. In Study 2, involving 18 participants, blood samples and symptom surveys were obtained before, during, and after front-line adjuvant chemotherapy. Digital polymerase chain reaction (PCR) was employed to assess serum CMV DNA (CMV DNAemia) levels, with a threshold of >100 copies/mL indicating active CMV infection. Meanwhile, the researchers evaluated CRCI using the Functional Assessment of Cancer Therapy–Cognitive Function (FACT-Cog) questionnaire. Changes in FACT-Cog scores were analyzed by CMV status at the time of diagnosis, employing t-tests at each time point.
The median (range) ages in each study were 59 (36-88) years in Study 1 and 58.5 (32-78) years in Study 2. Of note, most patients in the first study were non-Hispanic White (91.6%), while most were Hispanic or Latino in the second study (77.8%). Overall, most patients in both studies had stage III ovarian cancer, followed by stage IV, then stage I, then stage II. Additionally, the majority of patients had high-grade serious ovarian cancer. In Study 2 specifically, 5 of the patients had undergone neoadjuvant chemotherapy.
The studies revealed that, at the time of diagnosis, 29.2% of patients overall had active CMV infection, including 28.2% of patients in Study 1 and 33.3% of patients in Study 2. Additionally, 5.6% and 11.1% of patients in Study 1 and 2, respectively, were deemed CMV high, suggesting their infection occurred at least 4 months prior.
In Study 2, the percentage of patients with active CMV rose to 60% after patients went through 3 cycles of chemotherapy, then dropped back down to 31.3% 6 months after chemotherapy was finished. By the time chemotherapy was complete, 83.3% of patients in Study 2 had tested positive for CMV DNAemia at least once during treatment, with 55.6% testing positive more than once and 33.3% deemed CMV high at some point.
The researchers also noted significant alterations in self-reported cognitive functioning from baseline between patients who did or did not have CMV at the time of ovarian cancer diagnosis. Specifically, those with CMV at the time of diagnosis experienced a more pronounced decline in perceived cognitive impairments during chemotherapy (P = .027) and after chemotherapy was complete (P = .035) compared with patients who did not have CMV at diagnosis. Following chemotherapy, patients with CMV at baseline also reported more negatively impacted perceived cognitive abilities (P = .042) and comments from others (P = .046).
No differences were observed in the impact of perceived cognitive impairments on the quality of life subscale at any time point, and these results remained consistent even after adjusting for age at the time of diagnosis.
“It is unclear if CMV infection in particular is the culprit or if it is a biomarker for immune suppression,” the researchers said. “Regardless, the association of CMV with cancer mortality, its possible impact on patient symptoms, and available prevention and antiviral treatment strategies suggest the potential for high patient impact with further investigation in this population.”
Vogel RI, Stenzel AE, Lee H, et al. Prevalence of active cytomegalovirus infection at diagnosis of ovarian cancer and during chemotherapy and subsequent changes in cognitive functioning. BMC Cancer. 2023;23(1):1057. doi:10.1186/s12885-023-11566-y