Differential Mediating Roles of Immune-Inflammatory Cells in ≥HSIL Women: A Focus on HPV and CD4/CD8 or NLR

Yao Tong,1,2,* Yuqin Gao,3,* Xuanhao Wu,4 Yafang Kang,2,4,5 Huanrui Zheng,6 Rong Yu,7 Hui Zhong,8 Xiaodan Mao2,4,5 1Gynecology Department, Fujian Maternity and Child Health Hospital (Fujian Obstetrics and Gynecology Hospital), Fuzhou, Fujian, 350001, People’s Republic of China; 2Fujian Clinical Research Center for Gynecological Oncology, Fujian Maternity and Child Health Hospital (Fujian Obstetrics and Gynecology Hospital), Fuzhou, Fujian, 350001, People’s Republic of China; 3Department of Obstetrics and Gynecology, The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian, 350005, People’s Republic of China; 4Laboratory of Gynecologic Oncology, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, Fujian, 350001, People’s Republic of China; 5Fujian Key Laboratory of Women and Children’s Critical Diseases Research, Fujian Maternity and Child Health Hospital (Fujian Women and Children’s Hospital), Fuzhou, Fujian, 350001, People’s Republic of China; 6Department of Pharmacy, Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, 350001, People’s Republic of China; 7School and Hospital of Stomatology, Fujian Medical University, Fuzhou, Fujian, 350005, People’s Republic of China; 8Clinical Laboratory, Fujian Maternity and Child Health Hospital (Fujian Obstetrics and Gynecology Hospital), Fuzhou, Fujian, 350001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hui Zhong, Clinical Laboratory, Fujian Maternity and Child Health Hospital (Fujian Obstetrics and Gynecology Hospital), Fuzhou, Fujian, 350001, People’s Republic of China, Tel +0086-13599044659, Email [email protected] Xiaodan Mao, Fujian Clinical Research Center for Gynecological Oncology, Fujian Maternity and Child Health Hospital (Fujian Obstetrics and Gynecology Hospital), Fuzhou, Fujian, 350001, People’s Republic of China, Tel +0086-15959003652, Email [email protected]: This study aims to investigate the relationship between inflammatory-immune cells and ≥high-grade squamous intraepithelial lesions (HSIL), and to clarify the role of immune-inflammatory cells mediating human papilloma virus (HPV) and ≥HSIL.Methods: We retrospectively enrolled 427 patients with ≥HSIL and 357 ≤low-grade squamous intraepithelial lesions (LSIL) from June 1, 2013 to June 1, 2023. Clinical data such as age, peripheral blood inflammatory-immune cells, serum tumor markers, HPV infection status were collected to evaluate the relationship between clinical indicators and ≥HSIL mediated by inflammatory-immune cells.Results: Compared with the ≤LSIL cohort, the patients with ≥HSIL exhibited a significantly higher prevalence of infection with ≥ 2 type HPV genotypes compared to those with a single HPV infection (34.55% vs 17.65%, p = 0.045). Multiple HPV infection and lower CD4/CD8 ratio were the independent risk factors for the patients with ≥HSIL besides HPV infection. Moreover, the top three HPV genotypes were HPV-16, HPV-18 and HPV-52 among the populations of ≥HSIL. Interestingly, HPV (1.29%), HPV-16 (2.48%) and HPV-52 (9.70%) infection were partially mediated by CD4/CD8 ratio to promote ≥HSIL (p < 0.05). Furthermore, compared with the HSIL cohort, SCC, HPV16, HPV52 infection and higher neutrophil and lymphocyte ratio (NLR) were the independent risk factors for cervical cancer (CC). Among women with CC, the top three HPV types are 16, 18, and 52. The relationship between HPV/HPV-16 and CC was partially mediated by the NLR, with mediation effect ratios of 1.87% and 2.85%, respectively (p < 0.05).Conclusion: HPV-induced HSIL and CC are associated with immune-inflammatory status. Specifically, the CD4/CD8 ratio plays a significant mediating role during the HSIL stage, whereas NLR assumes a major mediating role in the CC stage. Thus, immune-inflammatory cells play distinct roles at different stages of CC progression.Keywords: cervical lesion, inflammatory-immune cells, multiple infection, HPV