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Recent Advances and Strategies for the Management of CIN and HPV Eradication Starategies for the Prevention of Uterine Cervical Cancer

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: 30 April 2026 | Viewed by 1715

Special Issue Editor


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Guest Editor
1. Department of Gynecology, Sasaki Foundation Kyoundo Hospital, Tokyo 101-0062, Japan
2. Department of Obstetrics and Gynecology, The Jikei University School of Medicine, Tokyo 105-8461, Japan
Interests: gynecologic oncology; pathogenesis of cervical cancer; HPV preventive vaccine; HPV therapeutic vaccine; endocervical conization; laser vaporization; PDT
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Special Issue Information

Dear Colleagues,

Managing cervical intraepithelial neoplasia (CIN) involves both treatment and follow-up, with HPV eradication strategies focused on preventing future infections through vaccination and early detection by regular screening. Every year, approximately 600,000 women worldwide are diagnosed with cervical cancer, and an estimated 340,000 women died from the disease in 2020. In Japan, however, the number of cervical cancer cases among women aged 20 to 39 is on the rise, alongside an increasing mortality rate. We invite you to submit research to this Special Issue titled “Recent Advances and Strategies for the Management of CIN and HPV Eradication Starategies for the Prevention of Uterine Cervical Cancer”, exploring the central theme of preventing uterine cervical cancer, divided into primary and secondary prevention. Primary prevention focuses on the use of HPV vaccines, while secondary prevention involves the diagnosis and management of CIN. We invite manuscripts related to vaccine trials (both preclinical and clinical) and strategies for developing more effective HPV vaccines. Our objective is to compile a range of research addressing the various aspects of HPV that could contribute to more effective strategies for eradicating HPV infection. Potential research areas include, but are not limited to, the following:

  • Diagnosis of CIN;
  • Gynecologic and obstetric risks;
  • Therapeutic effects of treatment.

We look forward to receiving your contributions.

You may choose our Joint Special Issue in Vaccines.

Dr. Masaru Sakamoto
Guest Editor

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • CIN
  • 9-valent HPV vaccine
  • HPV L2-VLP vaccine
  • HPV therapeutic vaccine
  • endocervical conization
  • laser vaporization
  • PDT

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Published Papers (1 paper)

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Research

21 pages, 2750 KB  
Article
T Cell Exhaustion in the Cervical Cancer Tumor Microenvironment: PD-1 Overexpression and Co-Expression with TIGIT, Tim-3, LAG-3, and NKG2A
by Nadia Tatiana García-Barrientos, Fabiola Solorzano-Ibarra, Ksenia Klimov-Kravtchenko, Jose Manuel Rojas-Diaz, Marcela Sofia Guitron-Aviña, Francisco Javier Ceja-Flores, Jose Alfonso Cruz-Ramos, Pablo Cesar Ortiz-Lazareno, Felipe de Jesús Bustos-Rodriguez, Juan Carlos Vazquez-Limon, Miriam Ruth Bueno-Topete, Martha Cecilia Tellez-Bañuelos, Jesse Haramati and Susana del Toro-Arreola
Cancers 2025, 17(22), 3627; https://doi.org/10.3390/cancers17223627 - 11 Nov 2025
Viewed by 1417
Abstract
Objective: T cell exhaustion is a major mechanism of immune evasion in cancer, characterized by the sustained expression of multiple inhibitory receptors. This study aimed to evaluate the expression of immune checkpoints in peripheral and tumor-infiltrating CD8+ T cells from cervical [...] Read more.
Objective: T cell exhaustion is a major mechanism of immune evasion in cancer, characterized by the sustained expression of multiple inhibitory receptors. This study aimed to evaluate the expression of immune checkpoints in peripheral and tumor-infiltrating CD8+ T cells from cervical cancer patients. Methods: We enrolled 104 participants: 37 treatment-naïve patients, 36 treated patients, and 31 age-matched healthy donors. Peripheral blood mononuclear cells (PBMCs) were isolated from all participants. Ten cervical biopsies were collected for tumor-infiltrating lymphocyte (TIL) isolation and paraffin fixation. Immune checkpoint expression was analyzed by multiparametric flow cytometry and immunohistochemistry. Results: In peripheral CD8+ T cells, we found a significant upregulation of exhaustion-associated markers PD-1, TIGIT, Tim-3, and LAG-3. In the tumor infiltrating lymphocytes, these same molecules, with the addition of NKG2A, were notably upregulated further. While BTLA and NKG2A showed no systemic changes, NKG2A increased in TILs and BTLA decreased in TILs. The co-expression of PD-1 with TIGIT, Tim-3, LAG-3, and NKG2A was notably enriched between 2- and 6-fold in TILs compared with patient PBMCs. The tumor microenvironment was highly immunosuppressive, characterized by enrichment with PD-1, PD-L1, and TIGIT; TIGIT was notably upregulated in locally advanced versus early-stage tumors. Conclusions: Our findings highlight the strongly immunosuppressive environment of cervical tumors in treatment-naïve patients and the presence of elevated inhibitory checkpoint expression in peripheral blood of both pre- and post-treatment patients. These results underscore the importance of investigating immune regulation within the tumor site itself and suggest that immune checkpoint co-expression may serve as a biomarker of T cell exhaustion and therapeutic resistance. Understanding how treatment alters these pathways could guide rational combination immunotherapies to restore CD8+ T cell function in cervical cancer. Full article
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