Gender‐neutral HPV elimination, cervical cancer screening, and treatment: Experience from Bhutan

Dorji, Thinley; Tshomo, Ugyen; Gyamtsho, Sonam; Tamang, Saran Tenzin; Wangmo, Sangay; Pongpirul, Krit

doi:10.1002/ijgo.13728

“…(2) There are few studies on PDIA3 and cervical cancer, and the role and specific mechanism of PDIA3 in the occurrence and development of cervical cancer remain unclear. (3) This study has demonstrated that the expression of PDIA3 in cervical cancer is up-regulated, and the high expression of PDIA3 is related to tumor progression, which may be an independent prognostic biomarker of cervical cancer.…”

Section: Data Availabilitymentioning

confidence: 75%

“…Most cervical cancer patients can be prevented from routine screening, such as human papillomavirus (HPV) vaccination, early screening, surgical treatment, chemoradiotherapy, and targeted therapy and treatment of precancerous lesions [1][2][3][4]. However, cervical cancer continues to be a serious threat to women's health and lives due to inadequate screening programmers in many parts of the world.…”

Section: Introductionmentioning

confidence: 99%

Expression and Prognostic Significance of PDIA3 in Cervical Cancer

Zhang

¹

,

Li

²

,

Li

³

et al. 2022

International Journal of Genomics

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To investigate the expression of protein disulfide isomerase A3 (PDIA3/ERP57) in cervical cancer and its clinical prognostic significance as well as its function and possible action mechanism in the progression of cervical cancer. Based on TIMER2.0 database, the human protein map (Human Protein Atlas) was used to determine the expression level of PDIA3 protein for the analysis of PDIA3 expression in 39 The Cancer Genome Atlas (TCGA) tumors. The PDIA3 expression in cervical cancer tissues in the TCGA and Genotype-Tissue Expression databases was further verified based on the GEPIA2 database to analyze the relationship between the PDIA3 expression and the pathological stage of cervical cancer patients. Immunohistochemistry was used to detect the PDIA3 expression in cervical cancer tissue microarray, including 111 cancer tissue samples and 24 adjacent cancer tissue samples, and the relationship between PDIA3 protein expression and clinical characteristics of patients with cervical cancer was analyzed. The Kaplan–Meier method and log-rank test were used for survival analysis. Based on the cBioPortal database, the Spearman’s and Pearson’s methods were used to analyze the correlation between PDIA3 expression and DNA methylation. The correlation between PDIA3 expression and the infiltration levels of each immune cell in cervical cancer was evaluated. The STRING was used to construct protein interaction network. Based on LinkedOmics database, the Spearman’s method was used to analyze the co-expressed genes of PDIA3 in TCGA cervical cancer. The gene ontology functional enrichment analysis was performed on Top 50 differentially co-expressed genes based on DAVID database. The PDIA3 expression in cervical cancer tissues was significantly higher than that in normal tissues, which ( F = 2.74 , PR (>F) = 0.0436) was significantly increased with the progression of tumor stage, and PDIA3 showed strong immunoreactivity in cervical cancer tissues. In cervical cancer patients, overall survival ( P = 0.014 ), disease-specific survival ( P = 0.013 ), disease-free interval ( P = 0.023 ), and progression-free interval ( P = 0.001 ) in those with high expression of PDIA3 were significantly lower than those with low expression, suggesting that high expression of PDIA3 was associated with poor prognosis. In cervical cancer, high expression of PDIA3 was associated with DNA methylation and negatively correlated with B cell memory ( r = − 0.132 , P = 0.021 ), T cell regulatory ( r = − 0.127 , P = 0.026 ), monocytes ( r = − 0.204 , P = 0 ), and macrophages M2 ( r = − 0.142 , P = 0.013 ), whereas positively correlated with levels of NK cell activated ( r = 0.162 , P = 0.005 ) and mast cells activated ( r = 0.119 , P = 0.037 ). The genes positively correlated with PDIA3 expression included HSPA5 and PPIB, which were mainly enriched in biological processes, such as endoplasmic reticulum (ER) protein folding and ER stress response. PDIA3 can be used as a marker of poor prognosis of cervical cancer. The expression level of PDIA3 is closely related to the survival and prognosis of cervical cancer patients, DNA methylation, and immune cell infiltration.

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“…Bhutan on the other hand was one of the first low to middle income countries to introduce a national HPV vaccination program in 2010, which also became sex neutral in 2020. However, despite being free of charge, screening uptake was only 59.2% among woman aged 18–69 years old and only increased to 66% in 2017, supporting the need for greater efforts to be implemented to achieve a higher vaccination rate ( 58 ).…”

Section: Secondary Prevention and Challenges Faced By Developing Coun...mentioning

confidence: 99%

Cervical cancer, geographical inequalities, prevention and barriers in resource depleted countries (Review)

Bogdanova

¹

,

Andrawos

²

,

Constantinou

³

2022

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Cervical cancer (CC) remains a current global issue, with >90% of cervical cancer cases being attributed to human papilloma virus (HPV). The highest burden of cervical cancer is reported in resource-depleted geographical areas with a high incidence of HPV infection. Recent developments in primary prevention include vaccinations against specific strains of HPV and the psychoeducation of the public. Yet, despite the availability of vaccinations, there is high incidence of both HPV and cervical cancer in developing countries, which is attributed to a multitude of barriers including inaccessibility to expensive vaccines. With regards to secondary prevention, progress is actively being made to develop more effective methods of screening and to specifically address the needs of low-income countries. In the past few years, more novel screening methods, such as self-assessment kits, immunohistochemistry and methylation marker analysis, have been developed. Barriers to screening in resource-depleted countries include limited financial resources and infrastructure to develop screening programmes, a lack of screening programmes that are accessible to populations, inadequate training of healthcare teams and stigma related to medical examinations performed as part of screening. Developing primary and secondary prevention programs, as well as addressing the barriers involved in countries with low socioeconomic levels, can drastically reduce morbidity and mortality rates associated with cervical cancer, thus reducing the burden associated with this gynaecological malignancy. Contents1. Introduction 2. Epidemiology and geographical inequalities in the burden of CC 3. Primary prevention and barriers faced by developing countries 4. Vaccinations 5. Psychoeducation 6. Secondary prevention and challenges faced by developing countries 7. Recent developments in screening methods 8. Barriers to screening in low resource countries and strategies for improvement 9. Conclusion

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“…This flagship program to eliminate cervical cancer has now also started by vaccinating adolescent boys and girls since 2020. 10 It is expected that major achievements, including reduction in incidence and mortality of cervical cancer, shall be achieved by the year 2030.…”

Section: Introductionmentioning

confidence: 99%