Search

Handoko,1– 3 Marlinda Adham,2,4 Lisnawati Rachmadi,2,5 Demak Lumban Tobing,6 Asmarinah,7 Fadilah,8 Wei Dai,9,10 Anne Wing Mui Lee,10 Soehartati A Gondhowiardjo2,3 1Doctoral Program in Biomedical Sciences, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; 2Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; 3Department of Radiation Oncology, Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia; 4Department of Otorhinolaryngology - Head and Neck Surgery, Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia; 5Department of Anatomical Pathology, Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia; 6Department of Clinical Pathology, Dharmais Cancer Hospital, Jakarta, Indonesia; 7Medical Biology Department, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia; 8Department of Medical Chemistry, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia-Bioinformatics Core Facilities, Indonesian Medical Education and Research Institute (IMERI), Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; 9Department of Clinical Oncology, University of Hong Kong, Pokfulam, Hong Kong (SAR), People’s Republic of China; 10Clinical Oncology Center, University of Hong Kong – Shenzhen Hospital, Shenzhen, People’s Republic of ChinaCorrespondence: Soehartati A Gondhowiardjo; Handoko, Email handoko12@ui.ac.idIntroduction: Nasopharyngeal cancer (NPC) is a multifaceted disease characterized by genetic and epigenetic modifications. While Epstein–Barr virus (EBV) infection is a known risk factor, recent studies highlight the significant role of DNA methylation in NPC pathogenesis. Aberrant methylation, particularly at CpG sites, can silence tumour suppressor genes, promoting uncontrolled cell growth. This study aims to analyse the methylation patterns in Indonesian NPC patients through whole-epigenome sequencing.Methods: Seven clinical nasopharyngeal cancer samples were collected and confirmed histopathologically. DNA was extracted, sequenced using Oxford Nanopore technology, and aligned to the GRCh38 human reference genome. Methylation analysis was performed using modkit and statistical analysis with R software. Enriched pathways and processes were identified using ClusterProfiler in R, and gene overlap analysis was conducted.Results: The analysis identified both globally hypermethylated and hypomethylated NPC samples. Key tumour suppressor genes, such as PRKCB, PLCB3, ITGB3, EPHA2, PLCE1, PRKCD, CDKN2A, CDKN2B, RPS6KA2, ERBB4, LRRC4, AKT1, PPP2R5C, and STK11 were frequently hypermethylated and confirmed to have lower expression in an independent NPC transcriptome cohort, suggesting their role in NPC carcinogenesis. Enriched KEGG pathways included PI3K-Akt signalling, ECM–receptor interaction, and focal adhesion. The presence of EBV DNA was confirmed in all samples, implicating its role in influencing methylation patterns.Discussion: This study provides comprehensive insights into the epigenetic landscape of NPC, underscoring the role of CpG methylation in tumour suppressor gene silencing. These findings pave the way for targeted therapies and highlight the need for region-specific approaches in NPC management.Keywords: nasopharyngeal cancer, epigenome, methylation, Epstein–Barr virus, whole-genome sequencing

Handoko,1– 3,* Marlinda Adham,2,4,* Lisnawati Rachmadi,2,5,* Heri Wibowo,6,* Soehartati A Gondhowiardjo1,2,* 1Department of Radiation Oncology, Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia; 2Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; 3Doctoral Program in Biomedical Sciences, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; 4Department of Otorhinolaryngology - Head and Neck Surgery Department, Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia; 5Department of Anatomical Pathology, Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia; 6Integrated Laboratory, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia*These authors contributed equally to this workCorrespondence: Soehartati A Gondhowiardjo, Faculty of Medicine, Universitas Indonesia, Jl. Salemba Raya No. 6, Jakarta, 10430, Indonesia, Email handoko12@ui.ac.id; gondhow@gmail.comIntroduction: Nasopharyngeal cancer (NPC) is a complex cancer due to its unique genomic features and association with the Epstein–Barr virus (EBV). Despite therapeutic advancements, NPC prognosis remains poor, necessitating a deeper understanding of its genomics. Here, we present a comprehensive whole genome sequencing (WGS) view of NPC genomics and its correlation with the phenotype.Methods: This study involved WGS of a clinical NPC biopsy specimen. Sequencing was carried out using a long read sequencer from Oxford Nanopore. Analysis of the variants involved correlation with the phenotype of NPC.Results: A loss of genes within chromosome 6 from copy number variation (CNV) was found. The lost genes included HLA-A, HLA-B, and HLA-C, which work in the antigen presentation process. This loss of the major histocompatibility complex (MHC) apparatus resulted in the tumour’s ability to evade immune recognition. The tumour exhibited an immunologically “cold” phenotype, with mild tumour-infiltrating lymphocytes, supporting the possible etiology of loss of antigen presentation capability. Furthermore, the driver mutation PIK3CA gene was identified along with various other gene variants affecting numerous signaling pathways.Discussion: Comprehensive WGS was able to detect various mutations and genomic losses, which could explain tumour progression and immune evasion ability. Furthermore, the study identified the loss of other genes related to cancer and immune pathways, emphasizing the complexity of NPC genomics. In conclusion, this study underscores the significance of MHC class I gene loss and its probable correlation with the cold tumour phenotype observed in NPC.Keywords: nasopharyngeal cancer, genomic, MHC class I, antigen processing and presentation, copy number variation, deletion

I Made Adi Parmana,1 Cindy Elfira Boom,1 Lisnawati Rachmadi,2 Dudy Arman Hanafy,3 Yunita Widyastuti,4 Muchtaruddin Mansyur,5 Bambang Budi Siswanto6 1Department of Anesthesiology and Intensive Care, National Cardiovascular Center Harapan Kita, Jakarta, Indonesia; 2Department of Anatomical Pathology, Faculty of Medicine, Universitas Indonesia/Dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia; 3Department of Cardiothoracic and Vascular Surgery, Faculty of Medicine, Universitas Indonesia/National Cardiovascular Center Harapan Kita, Jakarta, Indonesia; 4Department of Anesthesiology and Intensive Care, Universitas Gadjah Mada/Dr. Sardjito Hospital, Yogyakarta, Indonesia; 5Department of Community Medicine, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; 6Department of Cardiology and Vascular Medicine, Faculty of Medicine, Universitas Indonesia/National Cardiovascular Center Harapan Kita, Jakarta, IndonesiaCorrespondence: I Made Adi Parmana, Department of Anesthesiology and Intensive Care, National Cardiovascular Center Harapan Kita, LetJen S. Parman St No. Kav. 87, West Jakarta, Jakarta, Indonesia, Email adiparmana13@gmail.comPurpose: On-pump coronary artery bypass graft (CABG) causes myocardial ischemia, through the cardiopulmonary bypass (CPB) and aortic cross-clamping (AoX). Glutamine supplementation protects cardiac cells during cardiac ischemia. This study analysed the correlation between cardiac index (CI), plasma troponin I, myocardial histopathology, CPB and AoX duration in low ejection fraction patients receiving glutamine and no glutamine undergoing elective on-pump CABG.Material and Methods: This was a secondary analysis of a double-blind, randomised controlled trial of 60 patients, split into control and intervention (glutamine) groups. Glutamine was administered at a dose of 0.5 g/kg/24 hours. There were 29 patients in each respective groups after a total of two patients dropped out.Results: A negative correlation (p = 0.037) was observed between CPB duration and CI at 6 hours after CPB in the glutamine group. A positive correlation (p = 0.002) was also observed between AoX duration and plasma troponin I at 6 hours after CPB in the control group. However, no correlation was observed between myocardial histopathology and plasma troponin I level at 5 minutes after CPB.Conclusion: Significant negative correlation between CPB duration and CI at 6 hours after CPB in the glutamine group, along with significant positive correlation between AoX duration and plasma troponin I level at 6 hours after CPB in the control group demonstrated the myocardial protection qualities of intravenous glutamine administration in patients with low ejection fraction undergoing elective on-pump CABG surgeries.Keywords: glutamine, myocardial protection, coronary artery bypass grafting, cardiopulmonary bypass, low ejection fraction, myocardial injury

Made Susiyanti,1 Denisa Anggi Kurnia,1 Iqbal Fasha,2 Yunia Irawati,1 Lisnawati Rachmadi,3 Isabella Kurnia Liem,2,4 Widya Artini1 1Department of Ophthalmology, Faculty of Medicine, Universitas Indonesia – Cipto Mangunkusumo General Hospital, Jakarta, Indonesia; 2Cell Medical Technology Integrated Service Unit, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; 3Department of Anatomical Pathology, Faculty of Medicine, Universitas Indonesia – Cipto Mangunkusumo General Hospital, Jakarta, Indonesia; 4Department of Anatomy, Faculty of Medicine, Universitas Indonesia, Jakarta, IndonesiaCorrespondence: Widya Artini, Department of Ophthalmology, Faculty of Medicine, Universitas Indonesia – Cipto Mangunkusumo General Hospital, Jl. Kimia No. 8-10, RT.10/RW.1, Pegangsaan, Menteng, Jakarta Pusat, Jakarta, 10320, Indonesia, Tel +62 811841010, Email ikkesumantri@gmail.comPurpose: To evaluate the efficacy and safety of umbilical cord serum eye drops for dry eyes in ocular Stevens-Johnson Syndrome (SJS).Patients and Methods: A pre-post test study with umbilical cord serum (UCS) eye drop for ocular SJS patient with moderate to severe dry eyes. Study was conducted at Kirana Cipto Mangunkusumo General Hospital from June 2020 to December 2020. A total of five patients (five eyes) with a diagnosis of SJS more than 6 months, dry eye symptoms, and abnormal tear stability test results were included in the study. Each patient was asked to instill UCS drop into the affected eye six times daily. Evaluation of ocular symptoms with ocular surface disease index (OSDI) questionnaires, non-invasive tear break-up time (NIBUT), Schirmer I, and keratoepitheliopathy scores was administered before applying UCS drop and at week 2 and 4 of eye drop use.Results: From June 2020 to December 2020, five eyes of five patients were evaluated in this study. Patients were aged from 22 to 71 years old with history of SJS over periods from 1 to 35 years. Three patients underwent ocular surgeries prior to the study. After four weeks of treatment, symptoms score, Schirmer I, and keratoepitheliopathy scores improved significantly, while NIBUT scores improved insignificantly. No side effects were noted during treatment.Conclusion: Administration of UCS eye drop was effective in improving symptoms and signs of dry eye in chronic SJS patients.Keywords: umbilical cord serum eye drop, ocular Stevens-Johnson syndrome, dry eye

I Made Adi Parmana,1 Cindy Elfira Boom,1 Lisnawati Rachmadi,2 Dudy Arman Hanafy,3 Yunita Widyastuti,4 Muchtaruddin Mansyur,5 Bambang Budi Siswanto6 1Department of Anesthesiology and Intensive Care, National Cardiovascular Center Harapan Kita, Jakarta, Indonesia; 2Department of Anatomical Pathology, Faculty of Medicine, Universitas Indonesia/Dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia; 3Department of Cardiothoracic and Vascular Surgery, Faculty of Medicine, Universitas Indonesia/National Cardiovascular Center Harapan Kita, Jakarta, Indonesia; 4Department of Anesthesiology and Intensive Care, Universitas Gadjah Mada/Dr. Sardjito Hospital, Yogyakarta, Indonesia; 5Department of Community Medicine, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; 6Department of Cardiology and Vascular Medicine, Faculty of Medicine, Universitas Indonesia/National Cardiovascular Center Harapan Kita, Jakarta, IndonesiaCorrespondence: I Made Adi Parmana, Department of Anesthesiology and Intensive Care, National Cardiovascular Center Harapan Kita, LetJen S. Parman St No. Kav. 87, West Jakarta, Jakarta, Indonesia, Tel +62 812-4601-212, Email adiparmana13@gmail.comPurpose: Myocardial injury due to on-pump coronary artery bypass grafting (CABG) in patients with low ejection fraction (EF) is associated with poor outcomes. This study determines whether intravenous glutamine could protect the myocardium during on-pump CABG in patients with low EF.Materials and Methods: This was a double-blind, randomized controlled trial to assess glutamine as a myocardial protector during on-pump CABG in patients with left ventricle EF of 31– 50%, conducted from January to October 2021. Patients in the glutamine group (n = 30) received 0.5 g/kg of 20% glutamine solution diluted with 0.9% NaCl up to 500 mL in total volume over a period of 24 hours. Patients in the control group (n = 30) received 0.9% NaCl over the same period. The primary outcomes were plasma troponin I and plasma glutamine levels. Secondary outcomes included α-ketoglutarate (α-KG) levels and histopathology scoring of the right atrial appendage tissue, plasma lactate levels, hemodynamic measurement, and morbidity.Results: Twenty-nine patients from each group (58 in total) were included in the analysis. Plasma troponin I levels at 6 and 24 hours after cardiopulmonary bypass (CPB) were significantly lower in the glutamine than the control group (mean 3.43 ± 1.51 ng/mL vs mean 4.41 ± 1.89 ng/mL; p = 0.034; median 3.08 ng/mL [min–max: 1.30– 6.59] vs median 3.77 ng/mL [min–max: 0.00– 36.53]; p = 0.038, respectively). Plasma glutamine levels at 24 hours after CPB were significantly higher in the glutamine than the control group (mean 935.42 ± 319.10 μmol/L vs mean 634.79 ± 243.89 μmol/L, p = 0.001). Plasma lactate levels at 6 and 24 hours after CPB were significantly lower in the glutamine than the control group (median 5.30 mmol/L [min-max: 1.20– 9.50] vs median 5.70 mmol/L [min-max: 2.80– 11.30], p = 0.042; mean 2.08 ± 0.67 mmol/L vs mean 2.46 ± 0.69 mmol/L, p = 0.044, respectively). Myocardial injury score was significantly lower in the glutamine than the control group (mean 1.30 ± 0.24 vs mean 1.48 ± 0.26, p = 0.011).Conclusion: Perioperative administration of 0.5 g/kg intravenous glutamine solution over the period of 24 hours has myocardial protection effect in patients with low EF who undergo elective on-pump CABG.Keywords: glutamine, myocardial protection, coronary artery bypass grafting, cardiopulmonary bypass, low ejection fraction, myocardial injury

OBJECTIVE: Nasopharyngeal carcinoma (NPC) is a prevalent malignancy in Southeast Asia and Southern China, with a notable incidence in Indonesia. This study aimed to characterize the expression and correlation of Yes-associated protein (YAP1) and miR-340-5p in NPC metastasis tissues. MATERIALS AND METHODS: This study utilized clinical samples from primary tumors of NPC patients to investigate the expression of YAP1 and miR-340-5p. The Cancer Genome Atlas (TCGA) Head and Neck Cancer dataset was analyzed to assess YAP1 and miR-340-5p expression in broader head and neck cancer samples. Protein-protein interaction (PPI) and functional enrichment analyses were performed to understand the putative regulatory mechanisms of YAP1 and miR-340-5p head and neck cancer. YAP1 mRNA and miR-340-5p level expression were measured by reverse transcription- quantitative polymerase chain reaction (RT-qPCR), and statistical analyses were performed to compare the expression of these markers in NPC samples. RESULTS: Analysis of clinical samples revealed lower expression levels of YAP1 and miR- 340-5p in metastasis NPC cases compared to non-metastatic cases (p<0.0001). YAP1 and miR- 340-5p revealed a negative correlation in metastasis and non-metastasis samples but were statistically insignificant. Additionally, both genes showed significantly lower expression in stage IVB compared to stage II, III, and IVA NPC tissues (p<0.0001). The TCGA dataset showed consistent decreases in YAP1 and miR-340-5p expression in head and neck cancer tumors as opposed to normal tissues. Functional enrichment and PPI analysis suggested the involvement of the Hippo signaling pathway and other cancer-related pathways in NPC progression. CONCLUSIONS: The study highlights the under- expressed YAP1 and miR-340-5p in metastasis tumor cases, suggesting their potential role as a tumor suppressor in NPC. [ABSTRACT FROM AUTHOR]

Background: The exact cause of penile curvature in hypospadias remains unknown. Resection of the dartos fascia has been observed to straighten the penis, indicating the involvement of the dartos fascia in the superficial chordee. However, the characteristics of dartos tissue in the distal territory of the ventral penile shaft may differ from those in the proximal aspect of the penile shaft., Objective: This study aims to investigate the distinct histopathological profiles and expression of COL1A1 (collagen type 1), COL3A1 (collagen type 3), and ELN (elastin) in proximal and distal ventral dartos of patients with hypospadias compared to those without hypospadias., Methods: This prospective case-control study compares the ventral dartos tissue of patients with hypospadias at different locations with that of patients without hypospadias. Dartos samples will be taken during surgery, with age matching. Histopathology examination uses hematoxylin and eosin and Masson's trichrome stain. The mRNA expression of COL1A1, COL3A1, and ELN will be quantified using a 2-step reverse transcription-polymerase chain reaction analysis., Results: Previous studies have documented different characteristics of dartos tissue between patients with hypospadias and those without hypospadias. Some studies even suggest resection of the dartos tissue during hypospadias repair. However, this is the first study to compare the characteristics of ventral dartos tissue in patients with hypospadias based on its location along the penile shaft, suggesting potential differences between the distal and proximal locations. We have obtained ethical approval to conduct a prospective case-control study aimed at elucidating these differences in dartos tissue characteristics. The findings of the study are anticipated to be available by 2025., Conclusions: Differences in the characteristics of dartos fascia based on its location may require tailored surgical strategies. If the properties of distal dartos tissue closely mirror those of typical dartos tissue, the possibility of avoiding its excision during hypospadias surgery could be considered., International Registered Report Identifier (irrid): DERR1-10.2196/70075., (©Putu Angga Risky Raharja, Ponco Birowo, Lisnawati Rachmadi, Heri Wibowo, Aria Kekalih, Gede Wirya Kusuma Duarsa, Tariq Abbas, Irfan Wahyudi. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 18.02.2025.)

Background: Assessing perfusion in free flaps is crucial in clinical practice. Indocyanine green (ICG) angiography offers a more objective and reproducible method, utilizing near-infrared imaging to monitor flap vascularization. This study aims to evaluate the efficacy of diluted ICG as a tool for assessing free flap perfusion., Methods: This pilot randomized clinical trial compares the fluorescence concentrations of ICG at 3 different dilutions: 5 mg/mL (standard concentration), 2.5 mg/mL (half the standard concentration), and 0.5 mg/mL (one-tenth of the standard concentration). Inclusion criteria required participants to have serum albumin levels above 3 g/dL, hemoglobin levels over 10 g/dL, and no comorbidities. Participants were randomized into 3 groups based on ICG concentration. Fluorescence analysis was performed using ImageJ software to determine mean gray values. Both surgeons and data analysts were blinded to the ICG concentrations administered, ensuring unbiased evaluation., Results: Forty-five patients undergoing free flap surgery, predominantly male (60%) with a mean age of 37.76 ± 19.79 years and a mean body mass index of 21.23 ± 4.49 kg/m², primarily received osteoseptocutaneous fibular free flaps (46.67%), with an average skin flap area of 66.07 ± 46.94 cm². The primary etiology was underlying tumors (84.4%), with the head and neck as the most common reconstruction site (82.2%). The superior thyroid artery was the most frequently used recipient vessel (37.78%). Analysis revealed mean gray values of 64.10 ± 8.27 (5 mg/mL), 79.03 ± 2.7 (2.5 mg/mL), and 33.56 ± 3.47 (0.5 mg/mL), with 2.5 mg/mL yielding the highest value ( P < 0.001)., Conclusions: Findings suggest using 2.5 mg/mL concentration enhances fluorescence emission, offering a dosage alternative in clinical practice., Competing Interests: The authors have no financial interest to declare in relation to the content of this article. This work was supported by PUTI Q2 Grant from Universitas Indonesia. Disclosure statements are at the end of this article, following the correspondence information., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Objective: To investigate the relationship between Yes-Associated Protein (YAP) and Vascular Endothelial Growth Factor-A (VEGF-A) in nasopharyngeal carcinoma (NPC) and evaluate their potential as predictive biomarkers for distant metastasis., Methods: This observational analytic study was conducted from May to August 2023, including 60 NPC cases diagnosed histopathologically at the Department of Anatomical Pathology, Faculty of Medicine, Universitas Indonesia/Cipto Mangunkusumo Hospital. The study involved 30 NPC cases with distant metastasis and 30 without distant metastasis. Immunohistochemical analysis was performed using primary antibodies (rabbit YAP, D8H1X; mouse VEGF, clone C-1 sc-7269). Expression levels of YAP and VEGF-A were semi-quantitatively assessed using the H-score formula on 500 tumor cells. Cutoff points for YAP and VEGF-A were determined through Receiver Operating Characteristic (ROC) curve analysis and the Youden index. Statistical analyses, including Chi-square tests, were conducted using SPSS 25.0 to evaluate the relationship between marker expression and the presence of distant metastasis., Results: A significant difference in YAP expression was observed between NPC cases with distant metastasis (80%) and those without (23.3%, p<0.001). Similarly, VEGF-A expression was notably higher in cases with distant metastasis (86.7%) compared to those without (20%, p<0.001). A significant association between YAP and VEGF-A expression was found (p=0.001). ROC curve analysis showed that YAP (AUC=0.738, 95% CI 0.602-0.874) and VEGF-A (AUC=0.842, 95% CI 0.735-0.950) effectively predict distant metastasis. The double co-high-expression group (elevated YAP and VEGF-A) exhibited a significantly higher rate of distant metastasis compared to the non-double co-high-expression group (p<0.001)., Conclusion: Elevated expressions of YAP and VEGF-A are significantly associated with distant metastasis in NPC, suggesting their potential as biomarkers for predicting metastatic risk.

Radioresistance poses a significant challenge in the effective treatment of cervical cancer, often leading to poor patient outcomes. MicroRNA-21 (miR-21) and MicroRNA-145 (miR-145) are oncogenic micro-RNAs associated with various cancers, including cervical cancer, but their potential as predictive biomarkers for radioresistance remains underexplored. This study aimed to investigate the association between miR-21 and miR-145 expressions and the response to radiation therapy in cervical cancer patients. An analytical cross-sectional study was conducted on 140 subjects with cervical cancer stages IIIB and IVA who received definitive radiotherapy. miR-21 and miR-145 expressions were measured using real-time reverse transcriptase-polymerase chain reaction (RT-qPCR). A total of 102 subjects (72.9%) were classified as having stage III cervical cancer, and 38 subjects (27.1%) were classified as having stage IV cervical cancer. Disease progression occurred in 60.7% of subjects. The cut-off value for miR-21 expression was 0.00088 nmol/(mg/mL) (AUC 0.676, sensitivity 70.8%, specificity 50.8%), and a higher expression was significantly associated with radioresistance ( p = 0.010). miR-145, with a cut-off of 0.0239 nmol/(mg/mL) (AUC 0.612, sensitivity 67.5%, specificity 45.5%), showed no significant association with treatment response ( p = 0.132). Combining miR-21 and miR-145 (AUC 0.639, sensitivity 68.6%, specificity 46.9%, p = 0.063) did not significantly improve the predictive accuracy. This study suggests that an elevated miR-21 expression is significantly associated with radioresistance in cervical cancer patients, while miR-145 expression shows no significant correlation with treatment response. Additionally, combining miR-21 and miR-145 does not enhance the predictive power.

Background: The location and type of a tumor influence the prognosis of lung cancer. Primary Central Lung Tumors (PCLTs) are correlated with poor prognoses and certain histologic types. This study aimed to present a comprehensive exploration of clinical and bronchoscopic assessments for diagnosing the histopathology types of PCLTs and identified the factors associated with certain histologic types., Methods: This was an observational cross-sectional study of PCLTs, defined as tumors in direct contact with hilar structures or located within the inner two-thirds of the hemithorax. We gathered demographic and clinical data, as well as data on bronchoscopy assessment and histopathology type. Tumor stage, symptoms of superior vena cava syndrome, and enlargement of lymph nodes in the paratracheal and subcarinal regions were also documented., Results: Of the 895 patients, 37.87% had primary lung tumors, with 17.76% classified as PCLTs. Notably, PCLT cases exhibited a higher proportion of stage III (28.9% vs . 18.3%; p = 0.03) and Squamous Cell Carcinoma (SCC) histopathology (37.1% vs . 17.2%; p = 0.00) compared with non-PCLT cases. Bronchoscopic findings in PCLTs revealed a predilection for central airway masses (25.2%) and compressive distal airway stenosis (25.2%). Subgroup analysis of 159 PCLT cases identified 37.10% as SCC. Multivariate analysis underscored that intraluminal masses predict central SCC (odds ratio 2.075, 95% confidence interval 1.07-3.99; p = 0.028)., Conclusion: The proportion of stage III, SCC histopathological type, and intraluminal lesions was higher in patients with PCLT than in non-PCLT cases. The presence of intraluminal lesions can predict the histopathological type of SCC in patients with PCLTs., Competing Interests: The authors declare no conflict of interest, financial or otherwise., (© 2024 The Author(s). Published by Bentham Open.)

Background: The occurrence of castration-resistant prostate cancer (CRPC) varies in patients with advanced prostate cancer (PCa) undergoing androgen deprivation therapy (ADT). The rate of occurrence of CRPC may be related to the presence of prostate cancer stem cells (CSC). Thus, this study aims to evaluate the presence of CSC markers (CD44 and CD133) in histopathology tissue at the time of diagnosis and their correlation with the occurrence of CRPC in patients with advanced PCa within 2 years of ADT., Method: A retrospective case-control study was conducted to evaluate the incidence of CRPC within 2 years. The inclusion criteria were patients with PCa who had received treatment with ADT and a first-generation anti-androgen (AA) for 2 years. We classified patients based on whether they developed CRPC within 2 years (CRPC) of the therapy or did not experience CRPC within 2 years (non-CRPC) of the therapy. We performed immunohistochemical (IHC) staining for CD44 and CD133 on the prostate biopsy tissue samples., Results: Data were collected from records spanning 2011-2019. We analyzed a total of 65 samples, including 22 patients with CRPC and 43 patients with non-CRPC who had received treatment with LHRH agonists and AA for up to 2 years. Our findings showed a significant H-score difference in CD44 protein expression between CRPC prostate adenocarcinoma samples 869 (200-1329) and non-CRPC 524 (154-1166) (p = 0.033). There was no significant difference in CD133 protein expression between the two groups (p = 0.554). However, there was a significant difference in the nonoccurrence of CRPC between the high expressions of both CD44 and CD133 groups with other expressions of CD44/CD133 groups (25% vs. 75%; p = 0.011; odds ratio = 4.29; 95% confidence interval [1.34, 13.76])., Conclusion: This study found a low expression of at least one CD44/CD133 protein in the patients without early occurrence of CRPC. This result might suggest that CD44/CD133 may function as a potential prognostic marker for PCa, especially in a low expression, to identify patients who have a better prognosis regarding the occurrence of early CRPC., (© 2024 Wiley Periodicals LLC.)

Background: Triple-negative breast cancer (TNBC) has been documented as the most aggressive subtype of breast cancer. This study aimed to analyze antitumor and protumor immune activities, and their ratios as significant prognostic biomarkers in metastatic TNBC (mTNBC)., Methods: A multicenter cohort study was conducted among 103 de novo mTNBC patients. The expression of CD8 and CD163 was evaluated using immunohistochemistry staining, CD4 and FOXP3 using double-staining immunohistochemistry, and PD-L1 using immunohistochemistry and RT-PCR., Results: Multivariate analysis revealed that high CD4/FOXP3 (HR 1.857; 95% CI 1.049-3.288; p = 0.034) and the CD8/CD163 ratio (HR 2.089; 95% CI 1.174-3.717; p = 0.012) yield significantly improved 1 year overall survival (OS). Kaplan-Meier analysis showed that high levels of CD4 (p = 0.023), CD8 (p = 0.043), CD4/FOXP3 (p = 0.016), CD8/FOXP3 (p = 0.005), CD8/CD163 (p = 0.005) ratios were significantly associated with higher rate of 1 year OS. Furthermore, 1 year OS was directly correlated with antitumor CD4 (R = 0.233; p = 0.018) and CD8 (R = 0.219; p = 0.026) and was indirectly correlated with protumor CD163 and FOXP3 through CD4/FOXP3 (R = 0.282; p = 0.006), CD4/CD163 (R = 0.239; p = 0.015), CD8/FOXP3 (R = 0.260; p = 0.008), and CD8/CD163 (R = 0.258; p = 0.009)., Conclusion: This is the first study to demonstrate that high levels of CD4/FOXP3 and CD8/CD163 significantly improved the 1 year OS in de novo mTNBC patients. Thus, we recommend the application of these markers as prognosis determination and individual treatment decision., (© 2024. The Author(s).)

Purpose: : Ischemia-reperfusion injury (IRI) plays an important role in the pathophysiology of acute limb ischemia, leading to damage to distant organs, including the lungs. A complex mechanism is involved in the formation of reactive oxygen species (ROS), release of inflammatory mediators, and neutrophil activation. One strategy to reduce the damage is administering selenium, an antioxidant enzyme component that can bind ROS and protect cells. This study aimed to compare the degree of lung injury due to limb IRI in Sprague-Dawley (SD) rats with selenium administration versus those without selenium treatment., Materials and Methods: : Fifteen male SD rats were divided into three groups: the control group (Group A), the ischemia-reperfusion with pre-reperfusion selenium (Group B), and the ischemia-reperfusion with post-reperfusion selenium (Group C). All animals underwent two hours of limb ischemia and three hours of reperfusion. Selenium was given intravenously at a dose of 0.2 mg/kg body weight. After reperfusion, lung specimens were histopathologically examined., Results: : The median degree of lung injury was severe in Group A, mild in Group B, and moderate in Group C (P=0.01). Post hoc analysis revealed a significant difference in the degree of lung injury between Groups A and B (P=0.01), while a comparison between Groups A and C (P=0.06) and Groups B and C (P=0.31) revealed no significant difference., Conclusion: : The administration of pre-reperfusion selenium significantly decreases lung injury induced by limb ischemia-reperfusion in SD rats.

Background & Objective: The expression of matrix metalloproteinase-9 (MMP-9) and chemokine receptor 7 (CCR7) is significantly associated with tumor invasion and metastasis. Little is known regarding the potential of these markers in predicting cancer metastasis in Laryngeal Squamous Cell Carcinoma (LSCC). Therefore, this study aimed to dissect the potential of these markers in predicting the lymph node metastasis in LSCC patients., Methods: Sixty tissue samples were obtained from the patients diagnosed pathologically with LSCC who underwent partial or total laryngectomy. The expression of MMP-9 and CCR7 was measured using the immunohistochemistry staining in the tissue samples of LSCC patients. The ROC (receiver operating characteristic) curve was used to determine the most significant cut-off points of expression according to the highest sensitivity and specificity of both the markers to predict the lymph node metastasis in LSCC. Then, the relationship between the clinicopathology features and the expression of MMP-9 and CCR7 was evaluated., Results: The expression of both MMP-9 and CCR7 was significantly correlated with the lymph node metastasis in LSCC ( P <0.001). Furthermore, CCR7 expression exhibited the highest prediction accuracy (AUC 95.7%) and sensitivity (100%) in predicting the lymph node metastasis in LSCC compared to that of MMP-9 (AUC 92.9%, sensitivity 90%). We also found that patients with larger tumor size (> 4 cm) had significantly higher expression of MMP-9 and CCR7 ( P <0.002 and P <0.001, respectively). The Elevated expression level of CCR7 statistically correlated with higher MMP-9 expression ( P <0.001)., Conclusion: MMP-9 and CCR7 might be beneficial as predictors of lymph node metastasis in LSCC patients., Competing Interests: There are no conflict of interests declared by the authors.

Background: This study aims to describe the factors associated with dysplastic changes in sinonasal inverted papilloma (SIP) including somatic EGFR mutation, FoxM1 expression, HPV status, and their association with dysplastic changes., Methods: A cross-sectional, analytical study was conducted comprising 34 samples of histologically-confirmed diagnosis of SIP. The samples were further grouped into 2 groups: 20 samples without associated dysplastic changes, and 14 samples with associated dysplastic changes. The numbers of FoxM1 positively-expressed cells, EGFR mutation, and HPV status were compared among two groups using appropriate comparative statistics., Results: There was statistically-significant difference of FoxM1 expression between SIP and SIP with dysplasia (10% vs 100%; p<0.001). EGFR mutation was identified in 6 samples (30.0%) of the SIP and 5 samples (35.7%) of SIP with dysplasia. No difference of EGFR mutant proportion among two groups. HPV DNA was detected in 5 samples (25.0%) of SIP versus 9 samples (64.3%) of SIP with dysplasia. There was significant difference of HPV status among two groups (p=0.022). The high-risk subtypes were found in most HPV positive samples (57.1%), while low-risk subtypes and out panel subtypes were found 14.3% and 21.4%, respectively., Conclusions: FoxM1 was overexpressed in SIP with malignant transformation. FoxM1 along with HPV status is associated with dysplastic changes in the SIP. FoxM1 immunostaining is potential to be a biomarker of malignant transformation in SIP.

Objective: This study examine FOXP3, CD4, CD8 and p53 expression in the transformation of the Sinonasal Inverted Papilloma (SIP) malignancy into sinonasal carcinoma., Materials and Methods: This study used a cross-sectional approach. The research sample from thirty-six paraffin block preparations with the diagnosis of SIP. Then, immunohistochemical staining was performed using FOXP3 mouse monoclonal antibody (236A/E7), CD8 rabbit monoclonal antibody (CD8/1179R), CD4 mouse monoclonal antibody (4B12) and p53 rabbit monoclonal antibody.  Results: There was a significant difference between Foxp3 expression in SIP without dysplasia and SIP with dysplasia (p= 0.013). There was no significant difference between the expression of CD4 and CD8 in the two groups with p-values 0.1 and 0.062, respectively. The mean percentage of positive p53 expression in SIP without dysplasia was 0.45+0.63 and in the SIP with dysplasia 29.31+38.96. There was a significant difference between the two groups (p<0.001)., Conclusion: FOXP3 and p53 were overexpressed in SIP with malignant transformation. FOXP3 together with p53 status is associated with dysplastic changed in the SIP. FOXP3 and p53 status could be potential biomarker of malignant transformation in sinonasal inverted papilloma.

Introduction: EBV infection in nasopharyngeal cancer ensued in latent infection mode. In this latent infection various EBV oncoproteins such as EBNA1 and LMP1 was expressed. EBV oncoproteins could theoretically recruit immune cells, which might help to control cancer. Therefore, this study was aimed to elucidate the association with EBV oncoproteins (EBNA1 and LMP1), immune markers (CD4, CD8, and FOXP3) from nasopharyngeal cancer microenvironment with tumor progression., Method: Nasopharyngeal biopsy was obtained from patients suspected to have nasopharyngeal cancer. Those samples with microscopically confirmed nasopharyngeal cancer were tested for EBNA1, LMP1, CD4, CD8, and FOXP3 concentration with ELISA, then verified with IHC. Each patient tumor volume was assessed for primary nasopharyngeal tumor volume (GTVp) and neck nodal metastases tumor volume (GTVn). Correlation test with Spearman correlation and scatterplot were carried out., Result: Total 23 samples with nasopharyngeal cancer were analyzed. There was moderate correlation (ρ = 0.45; p value = 0.032) between LMP1 and GTVp. There was strong correlation (ρ = 0.81; p value < 0.001) between CD8 and GTVp. There was also moderate correlation (ρ = 0.6; p value = 0.002) between FOXP3 and GTVp. The CD8 concentration has moderate correlation with both EBNA1 (ρ = 0.46; p value = 0.026) and LMP1 (ρ = 0.47; p value = 0.023). While FOXP3 has moderate correlation with only LMP1 (ρ = 0.58; p value = 0.004). No correlation was found between all the markers tested here with GTVn., Discussion: We found larger primary nasopharyngeal tumor was associated with higher CD8 marker. This was thought due to the presence of abundance CD8 T cells in the nasopharynx, but those abundance CD8 T cells were suspected to be dysfunctional. The nasopharyngeal cancer was also known to upregulate chemokines that could recruit T regulatory FOXP3 cells. Furthermore, T regulatory FOXP3 cells differentiation was induced through several pathways which was triggered by EBNA1. The correlation found in this study could guide further study to understand nasopharyngeal carcinogenesis and the relationship with our immune system., (© 2022. The Author(s).)

Introduction: The incidence of nasopharyngeal cancer (NPC) is high, with new cases accounting for 5.2% of all malignancies in Indonesia. Most cases are detected at an advanced stage, and recurrences are common. Vascular endothelial growth factor (VEGF) and osteopontin (OPN) are important markers in tumorigenesis that serve as prognostic predictors. This study aims to determine the correlation of VEGF and OPN expression with 3-year progression-free survival (PFS)., Material and Methods: This retrospective cohort study analyzed 155 patients with locally advanced NPC. Data were obtained from medical records between 2015 and 2017. The locally advanced sample of this disease that met the inclusion criteria was stained with H&E before being prepared in a paraffin block. Furthermore, the immunohistochemistry staining results for VEGF and OPN were observed with ImageJ 1.50i and calculated semi-quantitatively using the histoscore., Results: The 3-year PFS obtained was 39%, with a median of 23 months. Vascular endothelial growth factor expression was detected in 113 of 155 samples (72.9%), while positive OPN expression was discovered in 99 of 155 samples (63.8%). There was a correlation between VEGF ( p = 0.747) and OPN expression ( p = 0.584) and 3-year PFS. Positive VEGF and OPN expression in the subgroup of patients with stage IVB and N3 tumors was related to improved 3-year PFS ( p < 0.05). This was similar to the positive VEGF expression in the subgroup of patients receiving neoadjuvant chemotherapy ( p < 0.05)., Conclusions: Vascular endothelial growth factor and OPN remained potential prognostic predictors in NPC. Patients with positive VEGF and OPN expression in N3, IVB, and neoadjuvant treatment had significantly improved 3-year PFS., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Termedia.)

Background: Cases of Human papillomavirus (HPV)-associated oral and oropharyngeal cancer are increasing. Proper diagnostic tools are required to detect HPV among patients, especially in areas where high technology is lacking., Aims: To provide mapping of HPV prevalence in Southeast Asia and to determine the effectivity of p16 as a surrogate biomarker for HPV infection in oral and oropharyngeal cancer., Methods: Medical records of 56 patients diagnosed with oral and oropharyngeal squamous cell carcinomas (SCC) were reviewed. HPV PCR DNA and p16 immunohistochemistry (IHC) examination were performed to detect HPV positivity., Results: HPV PCR prevalence in oropharyngeal SCC is 42.9% and 28.6% in oral SCC. P16 IHC has 67% sensitivity and 75% specificity in detecting HPV in oropharyngeal cancer, and 33% and 72% in oral cancer., Conclusion: We conclude that p16 IHC with a 5% cut-off can be used as a surrogate biomarker for oropharyngeal SCC, but not oral SCC, in areas where resources are restricted. However, further diagnostic tools may be needed.

Objectives: Persistent anal high-risk human papillomavirus (HR-HPV) infection is a major risk factor for anal cancer among MSM and transgender women (TGW). We aimed to estimate incidence, clearance, and persistence of anal HR-HPV in HIV-positive and HIV-negative MSM and TGW, and to assess factors for HR-HPV persistence., Design: Prospective cohort study., Methods: MSM and TGW aged at least 18 years, were enrolled from Indonesia, Malaysia, and Thailand, then followed up 6-monthly for 12 months. Anal swabs were collected at every visit for HR-HPV genotypes to define anal HR-HPV incidence, clearance, and persistence. Logistic regression was used to evaluate factors associated with HR-HPV persistence., Results: Three hundred and twenty-five MSM and TGW were included in this study, of whom 72.3% were HIV-positive. The incidence of anal HR-HPV persistence was higher in HIV-positive than HIV-negative MSM participants (28.4/1000 vs. 13.9/1000 person-months). HIV-positive participants had HR-HPV lower clearance rate than HIV-negative participants (OR 0.3; 95% CI 0.1-0.7). The overall persistence of HR-HPV was 39.9% in HIV-positive and 22.8% HIV-negative participants. HPV-16 was the most persistent HR-HPV in both HIV-positive and HIV-negative participants. HIV infection (aOR 2.87; 95% CI 1.47-5.61), living in Kuala Lumpur (aOR 4.99; 95% CI 2.22-11.19) and Bali (aOR 3.39; 95% CI 1.07-10.75), being employed/freelance (aOR 3.99; 95% CI 1.48-10.77), and not being circumcised (aOR 2.29; 95% CI 1.07-4.88) were independently associated with anal HR-HPV persistence., Conclusion: HIV-positive MSM and TGW had higher risk of persistent anal HR-HPV infection. Prevention program should be made available and prioritized for HIV-positive MSM and TGW where resources are limited.

Background: Nasopharyngeal cancer is endemic to Southeast Asia. However, there is limited clinical evidence of nasopharyngeal cancer in Indonesia, which has the largest population in Southeast Asia., Methods: Patterns of care and treatment outcomes in 428 patients with newly-diagnosed and pathologically-confirmed nasopharyngeal cancer were retrospectively analyzed., Results: Concurrent chemo-radiotherapy (CCRT) was the first-line treatment for stages I-IVB diseases. The 2-year overall survival (OS) of all patients were 100.0%, 100.0%, 93.8%, 86.2%, 82.9%, and 62.4% for stages I, II, III, IVA, IVB, and IVC, respectively. The 2-year OS of CCRT-treated patients were 100.0%, 100.0%, 92.6%, 82.4%, and 78.3% for stages I, II, III, IVA, and IVB, respectively., Conclusion: The patterns of care and treatment outcomes were potentially consistent with world standards, needing future validation. This is the largest study of newly diagnosed nasopharyngeal cancer in Indonesia, a huge disease burden, providing an important basis for the clinical management of this disease.

Tumor microenvironment have been implicated in many kind of cancers to hold an important role in determining treatment success especially with immunotherapy. In nasopharyngeal cancer, the prognostic role of this immune cells within tumor microenvironment is still doubtful. We conducted a study that included 25 nasopharyngeal cancer biopsy specimens to seek a more direct relationship between tumor infiltrating immune cells and tumor progression. Apart from that, we also checked the PD-L1 protein through immunohistochemistry. The PD-L1 was positively expressed in all our 25 samples with nasopharyngeal cancer WHO type 3 histology. Majority samples have >50% PD-L1 expression in tumor cells. We also found that denser local tumor infiltrating immune cells population have relatively much smaller local tumor volume. The inverse applied, with the mean local tumor volumes were 181.92 cm3 ± 81.45 cm3, 117.13 cm3 ± 88.72 cm3, and 55.13 cm3 ± 25.06 cm3 for mild, moderate, and heavy immune cells infiltration respectively (p = 0.013). Therefore, we concluded that tumor infiltrating immune cells play an important role in tumor progression, hence evaluating this simple and predictive factor may provide us with some valuable prognostic information., Competing Interests: The authors have declared that no competing interests exist.

Objectives: Cancer stem cells are involved in radioresistant cancers. Transcription factors Sry-related HMG box (SOX2) and octamer binding transcription factor 4 (OCT4) can confer pluripotent cell characteristics and self-renewal ability and are involved in carcinogenesis, metastasis, tumor recurrence, and resistance to therapy. Apoptosis, DNA repair, and telomerase factors also contribute to radioresistance. We sought to identify the role of SOX2 and OCT4 as cancer stem cell markers and their effects on apoptosis (via caspase 3), DNA repair (Chk1) and telomerase (hTERT) in conferring resistance to radiotherapy., Methods: We conducted a case-control study of 40 patients with stage IIIB cervical squamous cell carcinoma who completed radiation therapy at Cipto Mangunkusumo Hospital, Jakarta, Indonesia. The patients were classified according to their treatment response as having exhibited a complete or incomplete response. Clinical follow-up and Pap smears were performed between six and 12 months after therapy for those with a good initial response to determine the final response to therapy. Immunohistochemistry was used to analyze SOX2, OCT4, caspase-3, Chk1, and hTERT expression in paraffin sections of the initial biopsy., Results: Strong expression of SOX2 ( p = 0.011, p = 0.001) and OCT4 ( p < 0.001, p < 0.001) was significantly associated with both an incomplete initial and final therapy response, respectively. Multivariate analysis showed that SOX2 and OCT4 expression levels were the strongest markers of an incomplete response to radiotherapy (odds ratio (OR) = 5.12, p = 0.034, and OR = 17.03, p = 0.004, respectively)., Conclusions: Strong expression of SOX2 and OCT4 may be a good indicator of incomplete radiotherapy outcome in patients with stage IIIB cervical cancer.

Background: Overexpression of Rad51 protein in many tumor cells has been proven to increase radioresistance and can be related to the resistance of chemosensitivity of tumor cells. This preliminary study was conducted to determine the relationship between the Rad51 expression level in nasopharyngeal carcinoma and the response of the treatment based on the measurement of the tumor reduction., Methods: Thirteen cases of the NPCs were analyzed. The expression levels of the Rad51 were examined from the pretreatment biopsies. Furthermore, tumor reductions were determined based on the change in sum longest diameter of the nasopharyngeal CT-scan before and after therapy., Results: The expression level of the Rad51 was associated with the reduction of tumor mass. The P value was 0.049 and the correlation coefficient was 0.479., Conclusion: The tumor cells Rad51 expression levels may affect the tumor reduction of NPC after the therapy.

Background: Nasopharyngeal carcinoma (NPC) is endemic in Indonesia and 20% of the patients are diagnosed before the age of 31. This study evaluates presentation and treatment outcome of young patients in Jakarta, in a tertiary referral centre., Methods: Forty-nine patients under the age of 31, diagnosed with NPC between July 2004 and January 2007, were evaluated. Baseline data included histological type, stage of disease and presenting symptoms. We intended to follow all patients after diagnosis to reveal treatment outcome and overall survival (OS)., Results: All but two patients had advanced stage disease (94%), 7 (14%) had distant metastasis. The median interval between start of complaints and diagnosis was 9 months. Forty-two patients were planned for curative intent treatment. Eleven patients (26%) never started treatment, 2 patients did not complete treatment and 3 patients did not return after finishing treatment. Four patients died before radiation could start. Three patients died within 4 months after treatment. Nine patients (21%) had a complete response. Due to the high number of patients who were lost to follow-up (LFU), OS was analyzed as follows: a best-case (patients censored at last contact) and a worst-case scenario (assuming that patients who did not finish treatment or had disease at last contact would have died). The 2-year OS for patients without distant metastases was 39-71%., Conclusion: Treatment outcome for young patients with NPC in this institute was poor. Improvement can be achieved when NPC is diagnosed at an earlier stage and when there is better treatment compliance.

Purpose: Nasopharyngeal carcinoma (NPC) is consistently associated with Epstein-Barr virus (EBV) and highly prevalent in Indonesia. EBV-DNA load can be used for early diagnosis and may have prognostic value. In this study, EBV-DNA load was evaluated in minimal invasive nasopharyngeal (NP) brushings and whole blood for initial diagnosis and therapy assessment against the standard-of-care diagnosis by biopsy with EBV-RISH and standard EBV-IgA serology., Experimental Design: NP brushings and blood samples were collected from 289 consecutive ENT patients suspected of NPCs and 53 local healthy controls. EBV-DNA load was quantified by real-time PCR and serology by peptide-based EBV-IgA ELISA. Tissue biopsies were examined by routine histochemistry and by EBER RNA in situ hybridization., Results: Repeated NP brushing was well tolerated by patients and revealed high viral load in the 228 NPC cases at diagnosis than 61 non-NPC cancer cases and healthy controls (P < 0.001). The diagnostic value of EBV-DNA load in blood and EBV-IgA serology was inferior to the NP brush results. The level of EBV-DNA load in brushes of patients with NPC was not related to T, N, or M stage, whereas elevated EBV-DNA load in blood correlated with N and M stage. EBV-DNA levels in brushings and whole blood showed a significant reduction at 2 months after treatment (P = 0.001 and P = 0.005, respectively), which was not reflected in EBV-IgA serology., Conclusions: NP brush sampling combined with EBV-DNA load analysis is a minimal invasive and well-tolerated diagnostic procedure, suited for initial diagnosis and follow-up monitoring of NPCs.

Objective: Cervical cancer is the number one cause of cancer-associated death in Indonesian women (30/100,000 annually), where no screening program is present. The Papanicolaou test is widely accepted as an effective screening method for cervical neoplasia detection and often shows certain cytological features associated with human papillomavirus (HPV) infection. Especially in developing countries, cytological investigation is still the method of choice as compared to the frequent use of HPV DNA testing in western countries., Study Design: In the present study, we investigated the validity of the use of cytomorphological changes as a marker for HPV infection. A total of 140 smears collected in three different areas in Indonesia (Jakarta, Tasikmalaya and Bali) were analyzed. HPV DNA testing was performed using INNO-LiPA assays., Results and Conclusions: We found a highly significant association of classical koilocytosis, multinucleated cells, dyskeratosis-parakeratosis, nuclear membrane, enlarged nuclei, moderate/strong hyperchromasia and chromatin pattern with HPV positivity. Using classical and nonclassical cytomorphological parameters we found an overall sensitivity of 42% and a specificity of 90%. The combination of classical and nonclassical parameters led to a higher sensitivity of HPV positivity prediction. These results are of importance for cytologists in developing countries as molecular HPV testing still poses a major financial, logistic and expertise problem., (Copyright © 2012 S. Karger AG, Basel.)