Abstract:【Objective】To explore the relationship between high risk human papillomavirus (HR-HPV)-negative cervical lesions and cervical microenvironment. 【Methods】A total of 90 patients with HR-HPV negative cervical lesions were selected as the study subjects, including 26 patients with low-grade squamous intraepithelial lesion (LSIL group), 31 patients with high-grade squamous intraepithelial lesion (HSIL group), and 33 patients with cervical squamous cell carcinoma (CSCC group). The positive expression levels of CD4, CD8, Foxp3 and CD163 in the cervical lesions and the levels of IL-2 and IL-10 in the vaginal lavage fluid were detected and compared. 【Results】 Lactobacillus, Gardnerella and Bacillus were the most common vaginal flora in HPV negative cervical lesions; The detection rate of Lactobacillus in the CSCC group was lower than that in the LSIL group and the HSIL group, while the detection rate of Gardnerella and bacillus was higher than that in the LSIL group and the HSIL group. Compared with patients in LSIL and HSIL groups, the number of CD4+ T cells in cervical lesions of the CSCC group decreased, while the number of CD8+ T cells, Foxp3+ T cells and CD163+ tumor associated macrophages increased (P<0.05). Compared with the patients in the LSIL and HSIL groups, the level of IL-2 in vaginal lavage fluid in the CSCC group decreased, but the level of IL-10 increased (P<0.05). 【Conclusion】Vaginal micro ecology and immune imbalance are closely related to the progression of HR-HPV negative cervical lesions. Targeted treatment of vaginal infection and improvement of immunity can prevent the progression of cervical lesions.
[1] BARON C,HENRY M,TAMALET C,et al. Relationship between HPV 16,18,31,33,45 DNA detection and quantitation and E6/E7 mRNA detection among a series of cervical specimens with various degrees of histological lesions[J].J Med Virol,2015,87(8):1389-1396.
[2] BARRIENTOS-DURÁN A,FUENTES-LÓPEZ A.Reviewing the composition of vaginal microbiota:inclusion of nutrition and probiotic factors in the maintenance of eubiosis [J].Nutrients,2020,12(2):419.
[3] MOLIJN A,JENKINS D,CHEN W,et al. The complex relationship between human papillomavirus and cervical adenocarcinoma [J].Int J Cancer,2016,138(2):409-416.
[4] RODRÍGUEZ-CARUNCHIO L,SOVERAL I,STEENBERGEN R D,et al. HPV-negative carcinoma of the uterine cervix:a distinct type of cervical cancer with poor prognosis [J].BJOG,2015,122(1):119-127.
[5] MARTIN D H. The microbiota of the vagina and its influence on women's health and disease [J].Am J Med Sci,2012,343(1):2-9.
[6] BRADFORD L L,RAVEL J. The vaginal mycobiome:A contemporary perspective on fungi in women's health and diseases [J].Virulence,2017,8(3):342-351.
[7] JUNTTILA M R,DE SAUVAGE F J. Influence of tumour micro-environment heterogeneity on therapeutic response [J].Nature,2013,501(7467):346-354.
[8] RITU W,ENQI W,ZHENG S,et al. Evaluation of the associations between cervical microbiota and HPV infection,clearance,and persistence in cytologically normal women [J].Cancer Prev Res (Phila),2019,12(1):43-56.
[9] KYRGIOU M,MITRA A,MOSCICKI A B. Does the vaginal microbiota play a role in the development of cervical cancer? [J].Transl Res,2017,179:168-182.
[10] UNITT E,MARSHALL A,GELSON W,et al. Tumour lymphocytic infiltrate and recurrence of hepatocellular carcinoma following liver transplantation [J].J Hepatol,2006,45(2):246-253.
[11] ORMANDY L A,HILLEMANN T,WEDEMEYER H,et al. Increased populations of regulatory T cells in peripheral blood of patients with hepatocellular carcinoma [J].Cancer Res,2005,65(6):2457-2464.
[12] SUI X,MA J,HAN W,et al. The anticancer immune response of anti-PD-1/PD-L1 and the genetic determinants of response to anti-PD-1/PD-L1 antibodies in cancer patients [J].Oncotarget,2015,6(23):19393-19404.
[13] RUFFELL B,COUSSENS L M. Macrophages and therapeutic resistance in cancer [J].Cancer Cell,2015,27(4):462-472.
[14] CHEN X J,HAN L F,WU X G,et al. Clinical significance of CD163+ and CD68+ tumor-associated macrophages in high-risk HPV-related cervical cancer [J].J Cancer,2017,8(18):3868-3875.
[15] MURPHY K,MITCHELL C M. The interplay of host immunity,environment and the risk of bacterial vaginosis and associated reproductive health outcomes [J].J Infect Dis,2016,214(Suppl 1):S29-S35.
[16] ZHANG B,JIA H,LIU J,et al. Depletion of regulatory T cells facilitates growth of established tumors:a mechanism involving the regulation of myeloid-derived suppressor cells by lipoxin A4 [J].J Immunol,2010,185(12):7199-7206.