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      The correlation of HPV16 and HPV18 with local vaginal immunity after the treatment of cervical intraepithelial neoplasia

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          Abstract

          Background

          This study aimed to investigate the correlation between the level of HPV16 and HPV18 in patients with cervical lesions and the local vaginal immunity after receiving treatment with different degrees of cervical intraepithelial neoplasia (CIN) and cervical squamous cell carcinoma (CSCC).

          Methods

          One hundred and thirty-six patients with LSIL (grade 1 CIN or CIN 1), 263 patients with HSIL (grade 2 and 3 CIN or CIN 2 and 3), and 33 patients with CSCC pathologically confirmed between November 2012 and September 2016 were assigned to the test group and 100 healthy women in the same period were assigned to the control group. ELISA was used to determine the levels of SIgA, IgG, IL-2, and IL-10 and the IL-2/IL-10 ratio in vaginal lavage fluid in the test group (before treatment and 3, 6, and 12 months after treatment) and the control group, respectively. Gene chip technology was adopted to test the HPV infection in the test group (before treatment and 3, 6, and 12 months after treatment) and the control group, respectively.

          Results

          The results showed that the levels of SIgA, IgG, and IL-10 were positively correlated with the degree of cervical lesions and IL-2/IL-10 was negatively correlated with the degree in all patients before treatment. The levels of SIgA, IgG, and IL-10 were positively correlated with the degree of cervical lesions and IL-2/IL-10 was negatively correlated with the degree in HPV16 and HPV18-infected patients before receiving the treatment.

          Conclusions

          The recovery after the treatment of HPV infection is time-dependent and the immune system of patients with CIN starts to recover in the 6th month after treatment, early intervention is not recommended. However, the immune system is approximately in a normal sate at 12 months after treatment, at which time the efficacy can be evaluated, and clinical intervention can be initiated if necessary. The level of local immune factors in the vagina can be monitored to determine the progression and prognosis of patients’ cervical lesions.

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          A Cross-Talk Between Microbiota-Derived Short-Chain Fatty Acids and the Host Mucosal Immune System Regulates Intestinal Homeostasis and Inflammatory Bowel Disease

          Pedro Gonçalves, João Araújo, James Di Santo (2018)
          Gut microbiota has a fundamental role in the energy homeostasis of the host and is essential for proper "education" of the immune system. Intestinal microbial communities are able to ferment dietary fiber releasing short-chain fatty acids (SCFAs). The SCFAs, particularly butyrate (BT), regulate innate and adaptive immune cell generation, trafficing, and function. For example, BT has an anti-inflammatory effect by inhibiting the recruitment and proinflammatory activity of neutrophils, macrophages, dendritic cells, and effector T cells and by increasing the number and activity of regulatory T cells. Gut microbial dysbiosis, ie, a microbial community imbalance, has been suggested to play a role in the development of inflammatory bowel disease (IBD). The relationship between dysbiosis and IBD has been difficult to prove, especially in humans, and is probably complex and dynamic, rather than one of a simple cause and effect relationship. However, IBD patients have dysbiosis with reduced numbers of SCFAs-producing bacteria and reduced BT concentration that is linked to a marked increase in the number of proinflammatory immune cells in the gut mucosa of these patients. Thus, microbial dysbiosis and reduced BT concentration may be a factor in the emergence and severity of IBD. Understanding the relationship between microbial dysbiosis and reduced BT concentration to IBD may lead to novel therapeutic interventions.
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            Mucosal immunity: induction, dissemination, and effector functions.

            P Brandtzaeg (2009)
            Prevention of infections by vaccination remains a compelling goal to improve public health. Most infections involve the mucosae, but the development of vaccines against many of these pathogens has yet to be successful. Mucosal vaccines would make immunization procedures easier, be better suited for mass administration, and most efficiently induce immune exclusion - a term coined for non-inflammatory antibody shielding of internal body surfaces - mediated principally by secretory immunoglobulin A (SIgA). The exported antibodies are polymeric, mainly IgA dimers (pIgA) - produced by local plasma cells stimulated by antigens that target the mucosae. SIgA was early shown to be complexed with an epithelial glycoprotein - the secretory component (SC). In 1974, a common SC-dependent transport of pIgA and pentameric IgM was proposed. From the basolateral surface, pIg-SC complexes are taken up by endocytosis and finally extruded into the lumen. Membrane SC is now referred to as polymeric Ig receptor (pIgR). In 1980, it was shown to be synthesized as a larger transmembrane protein - first cloned from rabbit and then from human. Mice deficient for pIgR showed that this is the only receptor responsible for epithelial transport of IgA and IgM. In the gut, induction of B cells occurs in gut-associated lymphoid tissue, particularly the Peyer's patches, but also in mesenteric lymph nodes. Plasma cell differentiation is accomplished in the lamina propria to which the memory/effector cells home. The airways also receive such cells from nasopharynx-associated lymphoid tissue - but by different homing receptors. Such compartmentalization is a challenge for development of mucosal vaccines.
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              Linking cervicovaginal immune signatures, HPV and microbiota composition in cervical carcinogenesis in non-Hispanic and Hispanic women

              Paweł Łaniewski, Dominique Barnes, Alison Goulder … (2018)
              While high-risk human papillomavirus (HPV) infection is a well-established risk factor for cervical cancer, there are likely other factors within the local microenvironment that contribute to cervical carcinogenesis. Here we investigated relationships between HPV, vaginal pH, vaginal microbiota (VMB) composition, level of genital immune mediators and severity of cervical neoplasm. We enrolled women with low- and high-grade cervical dysplasia (LGD, HGD), invasive cervical carcinoma (ICC), and healthy controls. HPV16, HPV45, HPV58, and HPV31 were the most prevalent in our cohort with HPV16 and HPV31 genotypes more prevalent in Hispanics. Vaginal pH was associated with ethnicity and severity of cervical neoplasm. Lactobacillus dominance decreased with the severity of cervical neoplasm, which correlated with elevated vaginal pH. Hispanic ethnicity was also associated with decreased Lactobacillus dominance. Furthermore, Sneathia was enriched in all precancerous groups, ICC, abnormal pH and Hispanic origin. Patients with ICC, but not LGD and HGD, exhibited increased genital inflammatory scores and elevated specific immune mediators. Notably, IL-36γ was significantly associated with ICC. Our study revealed local, host immune and microbial signatures associated with cervical carcinogenesis and provides an initial step to understanding the complex interplay between mucosal inflammation, HPV persistence and the VMB.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Transl Cancer Res
                Journal ID (iso-abbrev): Transl Cancer Res
                Journal ID (publisher-id): TCR
                Title: Translational Cancer Research
                Publisher: AME Publishing Company
                ISSN (Print): 2218-676X
                ISSN (Electronic): 2219-6803
                Publication date (Print and electronic): July 2020
                Publication date (Print): July 2020
                Volume: 9
                Issue: 7
                Pages: 4212-4223
                Affiliations
                [1]deptDepartment of Obstetrics and Gynecology , Affiliated Hospital of Inner Mongolia Medical University , Inner Mongolia, China,
                Author notes

                Contributions: (I) Conception and design: L Mu, JR Miao; (II) Administrative support: JR Miao, JH Song; (III) Provision of study materials or patients: JR Miao, JH Song; (IV) Collection and assembly of data: L Mu; (V) Data analysis and interpretation: JR Miao; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

                [#]

                These authors contributed equally to this work.

                Correspondence to: Jing-Hui Song. Department of Obstetrics and Gynecology, Affiliated Hospital of Inner Mongolia Medical University, No. 1 of North Tongdao street, Huimin District, Inner Mongolia 100059, China. Email: jinghuisong277@ 123456163.com .
                Article
                Publisher ID: tcr-09-07-4212
                DOI: 10.21037/tcr-19-2955
                PMC ID: 8798840
                PubMed ID: 35117789
                SO-VID: c51e2041-013d-4047-b4f2-737004478729
                Copyright © 2020 Translational Cancer Research. All rights reserved.
                License:

                Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

                History
                Date received : 25 December 2019
                Date accepted : 05 June 2020
                Funding
                Funded by: National Natural Science Foundation of China
                Award ID: 81260095
                Funded by: Special Program of Health Industry, NHFPC
                Award ID: 201402010
                Categories
                Subject: Original Article

                Keywords: cervical intraepithelial neoplasia (cin),cervical squamous cell carcinoma,hpv 16,hpv 18,vaginal local immune factor
                Data availability:
                Keywords: cervical intraepithelial neoplasia (cin), cervical squamous cell carcinoma, hpv 16, hpv 18, vaginal local immune factor

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