Purpose: The ability to mount lymphoproliferative responses to peptides derived from the human papillomavirus (HPV) E6 and E7 oncoproteins has been associated with regression of dysplastic lesions of the uterine cervix and loss of associated HPV infection. Interleukin-12 (IL-12) is a potent immunopotentiator of T-cell function, and has been shown in phase I clinical trials to be tolerable.
Experimental Design: Patients were required to have measurable metastatic, recurrent or inoperable cervical carcinoma. Patients could have had one prior adjuvant regimen and one prior regimen for advanced disease. Treatment consisted of IL-12 administered at 250 ng/kg IV as a rapid push in the outpatient setting daily x 5 every 21 days. Whole blood samples were acquired twice before treatment then approximately every 3 weeks to assess lymphoproliferative response in vitro to HPV type 16 (HPV 16) E4, E6, and E7 peptides. These responses were correlated with demographics and with clinical outcome.
Results: Thirty-four patients were enrolled; 29 were evaluable. Over half had received cisplatin-based chemotherapy. The most common serious toxicities were hematologic or hepatic, and all were reversible. There was one partial responder (3%). The median survival was 6.5 months (95% CI: 5.8, 11.5 months). Eighteen of 29 eligible patients had evaluable laboratory data both pre- and post-therapy. There was a statistically significant increase in lymphoproliferative responses for HPV 16 E4, E6, and E7 peptides (P=0.020, 0.020, 0.043). There was a significant association between change in lymphoproliferative response to HPV 16 E6 peptides and number of cycles of treatment administered (P=0.048). There was no correlation between change in lymphoproliferative response to any peptide with age, performance status, race, prior chemotherapy, time from diagnosis to treatment, or with overall survival.
Conclusions: IL-12 treatment was associated with improved lymphoproliferative responses to HPV 16 E4, E6, and E7 peptides. This is the first clinical trial to demonstrate induction of cell-mediated immune (CMI) responses to specific antigens (peptides) following treatment with IL-12 in women with cervical cancer. This improvement in immune response was not associated with enhanced objective response or survival.
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http://dx.doi.org/10.1016/j.ygyno.2003.12.022 | DOI Listing |
Virol J
December 2024
Department of Stomatology, Affiliated Hospital of Hebei University, 212 Yuhua East Road, Baoding, 071000, Hebei, People's Republic of China.
Human papillomavirus (HPV) is the most prevalent sexually transmitted infection globally, with significant implications for various anogenital cancers, such as vulval, vaginal, anal, penile, head and neck cancers. HPV infections have been linked to the induction of inflammation. In contrast, Interleukin-37 (IL-37) is recognized as an anti-inflammatory cytokine.
View Article and Find Full Text PDF<b>Background and Objective:</b> Cervical cancer is the second most common cancer in Indonesia, where traditional herbal treatments like <i>Zanthoxylum acanthopodium</i> (andaliman) are culturally used. Investigating protein biomarkers such as E7, pRb, EGFR and p16 can help assess the efficacy of these treatments. <b>Materials and Methods:</b> There were 5 groups in this study: 2 control groups (C- and C+) and 3 treatment groups (each receiving one of three doses).
View Article and Find Full Text PDFGene
February 2025
Department of Biochemistry, Karpagam Academy of Higher Education, Coimbatore 641021, Tamil Nadu, India; Centre for Cancer Research, Karpagam Academy of Higher Education, Coimbatore 641021, Tamil Nadu, India. Electronic address:
The role of transforming growth factor-beta (TGF-β) is dual, such that, it inhibits tumor development in initial stage and promotes metastasis in later stage. The present study is aimed to analyse the relevance of different types of TGF-β and their receptors on the overall survival (OS) and TGF-β driven gene expression in individuals with cervical cancer (CC) using ONCODB and GEPIA databases. The in-silico gene expression analysis showed, TGF-β1 and TGFβR2 are upregulated in cells infected with human papilloma virus (HPV)16, whereas, TGF-β2, TGFβR1 and TGFβR3 expression were downregulated.
View Article and Find Full Text PDFRev Bras Ginecol Obstet
December 2024
Universidade Federal de Ciências da Saúde de Porto Alegre Porto AlegreRS Brazil Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS, Brazil.
Objective: The average age of patients with vulvar squamous cell carcinoma (SCC) has been reported to have declined. Human papilloma virus (HPV)-related lesions have been shown to be associated with the expression of the immunohistochemical (IHC) marker p16. Non-HPV-related tumors have been characterized by p53 abnormal expression and PDL1 expression.
View Article and Find Full Text PDFClinics (Sao Paulo)
December 2024
Department of Gynecology, Hangzhou Geriatric Hospital, Hangzhou, 310022, Zhejiang, China. Electronic address:
Introduction: Cervical Human Papillomavirus (HPV) infection, a common sexually transmitted infection, can lead to cervical cancer. This study investigates the impact of Photodynamic Therapy (PDT) on cellular immune function in cervical HPV-infected patients.
Methods: From October 2022 to February 2023, 60 patients with cervical HPV infection were randomly assigned to a control group (conventional treatment) or a PDT group (PDT treatment), each with 30 patients.
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