Systemic Immune-Inflammation Markers Associate With Cervical Human Papillomavirus Infection in Asymptomatic Women

Human papillomavirus (HPV), a major cause of cervical cancer, typically remains localized to the cervix. However, there is limited understanding of whether this localized infection is associated with systemic immune responses in asymptomatic women, beyond the immediate cervical microenvironment. This study aimed to assess whether systemic immune-inflammation markers are linked to HPV infection and HPV-related cytological abnormalities in asymptomatic women undergoing health screening.

This cross-sectional study included women from the Kangbuk Samsung Health Study who underwent HPV DNA testing and cervical cytology between 2016 and 2022. Participants were categorized as H0C0 (HPV-negative and normal cytology), H1C0 (HPV-positive and normal cytology), and H1C1 (HPV-positive and abnormal cytology, defined as low-grade abnormalities, including atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesions). Systemic immune-inflammation markers, including white blood cell-derived indices, high-sensitivity C-reactive protein, systemic inflammation response index (SIRI), lymphocyte-to-monocyte ratio (LMR), and neutrophil-to-monocyte ratio (NMR), were analyzed. Multinomial logistic regression was used to estimate the odds ratios (ORs) by biomarker quintiles and per 1-standard deviation (SD) increase.

Among 145 889 women (mean age 40.4 years), 6535 were classified as H1C0 and 2820 were classified as H1C1. Individuals with higher monocyte counts (Q5 vs Q1) had a significantly higher risk of H1C0 (OR = 1.14, 95% confidence interval [CI]: 1.06-1.24) and H1C1 (OR = 1.22, 95% CI: 1.08-1.37). Similarly, SIRI was positively associated with HPV infection status, with increasing odds for both H1C0 and H1C1 compared with H0C0, whereas LMR and NMR were inversely associated with H1C1. Per 1-SD increase, LMR was inversely associated with both H1C0 (OR = 0.71, 95% CI: 0.59-0.87) and H1C1 (OR = 0.48, 95% CI: 0.35-0.65), while monocyte count showed a positive association.

Human papillomavirus infection was associated with systemic immune-inflammatory changes, most notably elevated monocyte count and related indices, even in individuals without cytological abnormalities. These findings highlight the potential relevance of monocyte-related markers for capturing the systemic immune effects of HPV infection beyond localized cervical changes.