Pulsatility Index and Hypoxia Inducible Factor-1α Expression Predict the Clinical Response after External Radiation in Patients with Stage IIB to IVA Cervical Cancer

Background: Incidence of cervical cancer is higher in low- and middle-income countries, including Indonesia. In Asia, Indonesia ranks second both in mortality and incidence of cervical cancer. Infection by Human Papilloma Virus (HPV) type 16 is a known risk factor, especially with mutations of the E6 or E7 oncogene that lead to chronic infection and malignancy. Increase in cyclin D1 expression is found on cervical cancer cells, including those resistant to chemotherapy. The role of cyclic D1 in increasing cellular proliferation and decreasing apoptosis leads to cervical cancer. Methods: This study was a cross-sectional observational study carried out between August 2020 until August 2021 at Prof. Dr. I.G.N.G. Ngoerah Hospital, Denpasar, Bali, Indonesia. Samples were collected by consecutive sampling of eligible patients. Polyclinic patients newly diagnosed with cervical cancer and who gave informed consent were further examined. We determined their oncogene E6 and E7 HPV type 16 mutation patterns and their association with cyclin D1 expression using contingency coefficient correlation test. Other outcomes including age distribution, parturition history, BMI, pathological type, clinical stage, and E6/E7 mutation characteristics was also recorded. Results: We included 31 eligible subjects with cervical cancer and HPV type 16-positive, divided into mutant E6/E7 (n=12/31; 38.7%) and wild type (n=19/31;61.3%). Primary outcome of association between mutant oncogene and cyclin D1 expression was weak (c=0.283; p-value=0.1). Secondary outcome showed majority of age on 50 years old or over; normal or overweight BMI; squamous cell carcinoma was the most commonly found (n=28/31; 90%); and clinical stage II (n=18/31; 38%) in both groups. Conclusions: This study concluded that there is no association between mutation in the E6/E7 HPV type 16 oncogenes with cyclin D1 expression in patients with cervical cancer.

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Association between mutant E6 and E7 Human Papilloma Virus Type 16 oncogenes with cyclin D1 expression in cervical cancer: Observational study in Bali

Mahendra

Budiana

Putra

et al. 2023

F1000Res

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Association of HPV Genotyping with HIF1-Alpha in Advanced Cervical Cancer on Response to Radiotherapy

Anfasa

Suardi

Salima

et al. 2023

Open Access Maced J Med Sci

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AIM: This study aims to determine the relationship between the HPV genotype in uterine cervical cancer and the expression of HIF-1α due to tissue hypoxia and its impact on radiation response. METHODS: This study is an analytic and observational study with a cross-sectional design with the inclusion criteria in this study that was new cervical cancer Stage IIB, IIIA, IIIB, and IVA patients treated at the oncology polyclinic who had never undergone radiotherapy and would be treated with radiation. RESULTS: Sixty patients advanced cervical cancer aged 25 to >45 years were involved patients. The majority had HPV genotype 16 infections. There was no significant relationship between treatment response and HPV genotype (HPV 16 genotype [p = 0.844], HPV 18 genotype [p = 0.161], other HPV genotypes [p = 0.108]), radiation response with HIF-1α expression (p = 0.503; OR 1.569 [0.417–5.899]), HIF1α expression with HPV genotype (HPV genotype 16 (p = 0.648; OR 1,357 [0.356–5.041]), HPV 18 genotype (p = 0.344; OR 1,458 [0.089–2.373]), and other HPV genotypes (p = 0.505; OR 1.667 [0.368–7.553]) as well as HIF-1α expression and HPV genotypes to radiation response (p > 0.05). CONCLUSION: Cervical cancer with infection with HPV Genotype 18 tends to express HIF1α strongly and increased partial radiation response. Overall statistically, there was no significant association between infection with certain genotypes of HPV with radiation response or HIF-1α expression in tumor tissue with radiation response.

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Role of Oxygenation Factor Hypoxia-inducible Factor-1α (HIF-1α) as Prognostic Indicators in Cervical Cancer

Megadhana,

Winata,

Widiyanti

et al. 2023

Journal of South Asian Federation of Obstetrics and Gynaecology

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Objective: This literature aims to know the role of HIF-1a as a prognostic indicator of oxygenation in cervical cancer. Materials and methods: All references used in this literature review were searched in several databases such as PubMed (Medline), Google Scholar, and ScienceDirect. Results: Hypoxia can cause damage to cell death because the body's cells are very dependent on the oxygen constant supply to function and survive. Hypoxia inducible factor-1α plays an important role in tumor development through the regulation of gene expression (angiogenesis, cell survival, and drug resistance) especially under hypoxemic conditions such as embryogenesis, cardiovascular disease, and carcinogenesis. High HIF-1α expression can cause a decrease in tumor latency, an increase in blood vessel density, tumor volume, and tumor permeability, and promote tumor growth, while a decrease in HIF-1α activity will cause a decrease in growth progression, vascularization, and energy metabolism. Conclusion:The use of gene expression induced by hypoxia as a biomarker for tumor hypoxia has been investigated especially HIF-1α, which regulates tumor cell metabolism and metastasis in hypoxic states. The HIF-1α protein also contributes to more progressive tumor growth and it is possible that this effect is synergistic with the human papillomavirus (HPV) oncogene. Several studies have stated a strong relationship between HIF-1α protein and cancer.

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Pulsatility Index and Hypoxia Inducible Factor-1α Expression Predict the Clinical Response after External Radiation in Patients with Stage IIB to IVA Cervical Cancer

Cited by 3 publications

References 19 publications

Association between mutant E6 and E7 Human Papilloma Virus Type 16 oncogenes with cyclin D1 expression in cervical cancer: Observational study in Bali

Association between mutant E6 and E7 Human Papilloma Virus Type 16 oncogenes with cyclin D1 expression in cervical cancer: Observational study in Bali

Association of HPV Genotyping with HIF1-Alpha in Advanced Cervical Cancer on Response to Radiotherapy

Role of Oxygenation Factor Hypoxia-inducible Factor-1α (HIF-1α) as Prognostic Indicators in Cervical Cancer

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