Blood-Based FTIR Spectroscopy as a Minimally Invasive Diagnostic Method for Colorectal Cancer: A Meta-Analysis.

OBJECTIVE: This meta-analysis aims to pool the results of existing studies to obtain more precise estimates on the diagnostic efficiency of the Fourier transform infrared (FTIR) spectroscopy in detecting CRC using blood-based samples. METHODS: A comprehensive database search identified 4,931 studies that were screened for eligibility. Relevant data were then extracted and collated and analyzed using Meta-DiSc 1.4 to measure the pooled diagnostic accuracy, sensitivity, specificity, likelihood ratio, and diagnostic odds ratio and presented in forest plots. RESULTS: The pooled sensitivity across all six data entries was 86.10% (p = 0.20), and the specificity was 91.2% (p < 0.001). The pooled positive likelihood ratio was 9.84 (p < 0.001), indicating a strongly moderate diagnostic value, while the negative likelihood ratio was 0.16 (0.12), suggesting moderately decreased efficacy of FTIR spectroscopy in ruling out the disease. The pooled AUC was found to be at 0.94 which indicate excellent discriminating potential of FTIR of the method. CONCLUSION: Overall, the study suggests that FTIR spectroscopy has potential as minimally invasive diagnostic method for CRC using plasma samples.

Expression of specific microRNAs in tissue and plasma in colorectal cancer.

BACKGROUND: MicroRNAs (miRNA/miR) play significant roles in the regulation of cell differentiation, cell cycle progression, and apoptosis. They become dysregulated during carcinogenesis and are eventually released into the circulation, enabling their detection in body fluids. Thus, this study compared the miRNA expression in tissue and plasma samples of colorectal cancer (CRC) patients and clinically healthy controls and determined miRNA expression as a potential CRC biomarker. METHODS: Using quantitative reverse transcription polymerase chain reaction (RT-qPCR), miR-21-5p, miR-29a-3p, miR-92a-3p, miR-135b-5p, miR-196b-5p, and miR-197-3p, expression was analyzed and compared between the malignant (n = 41) and the adjacent neoplasm free mucosal tissues (n = 41) of CRC patients. The findings were validated in plasma samples (n = 36) collected from the same CRC patients prior to surgery or any form of treatment and compared to plasma from their age and sex-matched controls (n = 36). RESULTS: MiR-21-5p, miR-29a-3p, miR-92a-3p, and miR- 196b-5p were upregulated and miR-135b-5p was downregulated in CRC malignant tissues compared to their expression in adjacent neoplasm-free tissue. This was further observed in the plasma of the same CRC cases compared to controls. MiR-92a-3p showed itself the most sensitive (0.93; p < .001) and most specific (0.95; p < .001) in detecting CRC in tissue. In plasma, miR-196b-5p was the most sensitive (0.97; p < .001) and specific (0.94; p < .001) in detecting CRC. Plasma miR-92a-3p and miR-196b-5p were the most sensitive (0.95; p < .001) and specific (0.94; p < .001) in the early detection of CRC. CONCLUSIONS: Results show that specific miRNAs dysregulated in malignant tissues are released and can be detected in the circulation, supporting their potential as non-invasive biomarkers of CRC.

A Meta-Analysis on the Association of Colibactin-Producing pks+ Escherichia coli with the Development of Colorectal Cancer.

OBJECTIVE: Previous studies on the association between pks+Escherichia coli and colorectal cancer (CRC) demonstrated conflicting results. Hence, we performed a meta-analysis to obtain more precise estimates. METHODS: Related literature was obtained from PubMed, ScienceDirect, Google Scholar, and Cochrane Library. Data were then extracted, summarized, and subjected to analysis using Review Manager 5.4 by computing for the pooled odds ratios at the 95% confidence interval. RESULTS: Overall analysis showed that individuals carrying pks+E coli had a greater risk of developing CRC. Subgroup analysis further showed that individuals from Western countries carrying pks+E coli and individuals with pks+E coli in their tissue samples had increased risk of developing CRC. CONCLUSION: Results of this meta-analysis suggest that individuals with pks+E coli have a greater risk of developing CRC. However, more studies are needed to confirm our claims.

Diagnostic Efficiency of Serum-Based Infrared Spectroscopy in Detecting Breast Cancer: A Meta-Analysis.

BACKGROUND: The advancement of Fourier transform infrared (FTIR) spectroscopy as a potential diagnostic tool in the clinical setting has been studied over the years, particularly its application in cancer diagnostics. OBJECTIVE: To summarize previous research on FTIR spectroscopy in detecting breast cancer using serum specimens. METHODS: Related literature was searched and screened from various databases. Relevant data were then extracted, tabulated, and analyzed using Meta-DiSc 1.4 software. RESULTS: Sensitivity and specificity rates were 90% to 100% and 80% to 95%, respectively. The area under the receiver operating characteristic curve was at 0.9729, indicating that serum analysis via FTIR spectroscopy can accurately discriminate between healthy individuals and patients with breast cancer. CONCLUSION: Overall, FTIR spectroscopy for breast cancer diagnosis using serum specimens shows promising results. However, further studies are still needed to validate these claims.

Antibody response to enterotoxigenic Bacteroides fragilis of Filipino colorectal cancer patients.

Background: Several species of the gut microbiota have been implicated in colorectal cancer (CRC) development. The anaerobic bacterium enterotoxigenic Bacteroides fragilis (ETBF), has been identified to produce fragilysin, a toxin known to cleave E-cadherin, thereby leading to carcinogenesis. Objective: To determine the antibody response of CRC patients against ETBF to ascertain whether significant difference exists or whether antibody response is related to tumor grade and tumor stage. Methods: Informed consent was obtained from histologically confirmed CRC casesand their age- and sex-matched clinically healthy controls. Plasma samples from the participants were subjected to in-house enzyme-linked immunosorbent assay (ELISA) to determine their antibody levels. Results: Using ETBF total protein as coating antigen, 38/39 (97%) CRC cases and 36/39 (92%) controls showed anti-ETBF IgG above cut-off, while all (100%) CRC cases and 36/39 (92%) controls had anti-ETBF IgA levels above cut-off. With culture broth as coating antigen, all (100%) CRC cases and 37/39 (95%) controls had anti-ETBF IgG levels above cut-off. For anti-ETBF IgA, all (100%) cases and controls had levels above cut-off. Statistical analysis reveals no significant difference (P > 0.05) on the number of CRC cases and controls with IgG and IgA antibody levels above cut-off value. Also, there's no significant difference (P > 0.05) in the mean anti-ETBF antibody levels of cases who were at different tumor grade (well differentiated and moderately and poorly differentiated) and tumor stage (early and advanced). Conclusions: These results suggest that Filipino CRC cases and their clinically healthy matched controls exhibit antibody responses against ETBF.

Predicting the Likelihood of Colorectal Cancer with Artificial Intelligence Tools Using Fourier Transform Infrared Signals Obtained from Tumor Samples.

The early and accurate detection of colorectal cancer (CRC) significantly affects its prognosis and clinical management. However, current standard diagnostic procedures for CRC often lack sensitivity and specificity since most rely on visual examination. Hence, there is a need to develop more accurate methods for its diagnosis. Support vector machine (SVM) and feedforward neural network (FNN) models were designed using the Fourier transform infrared (FT-IR) spectral data of several colorectal tissues that were unanimously identified as either benign or malignant by different unrelated pathologists. The set of samples in which the pathologists had discordant readings were then analyzed using the AI models described above. Between the SVM and NN models, the NN model was able to outperform the SVM model based on their prediction confidence scores. Using the spectral data of the concordant samples as training set, the FNN was able to predict the histologically diagnosed malignant tissues (n = 118) at 59.9-99.9% confidence (average = 93.5%). Of the 118 samples, 84 (71.18%) were classified with an above average confidence score, 34 (28.81%) classified below the average confidence score, and none was misclassified. Moreover, it was able to correctly identify the histologically confirmed benign samples (n = 83) at 51.5-99.7% confidence (average = 91.64%). Of the 83 samples, 60 (72.29%) were classified with an above average confidence score, 22 (26.51%) classified below the average confidence score, and only 1 sample (1.20%) was misclassified. The study provides additional proof of the ability of attenuated total reflection (ATR) FT-IR enhanced by AI tools to predict the likelihood of CRC without dependence on morphological changes in tissues.

Artificial neural network in the discrimination of lung cancer based on infrared spectroscopy.

Given the increasing prevalence of lung cancer worldwide, an auxiliary diagnostic method is needed alongside the microscopic examination of biopsy samples, which is dependent on the skills and experience of pathologists. Thus, this study aimed to advance lung cancer diagnosis by developing five (5) artificial neural network (NN) models that can discriminate malignant from benign samples based on infrared spectral data of lung tumors (n = 122; 56 malignant, 66 benign). NNs were benchmarked with classical machine learning (CML) models. Stratified 10-fold cross-validation was performed to evaluate the NN models, and the performance metrics-area under the curve (AUC), accuracy (ACC) positive predictive value (PPV), negative predictive value (NPV), specificity rate (SR), and recall rate (RR)-were averaged for comparison. All NNs were able to outperform the CML models, however, support vector machine is relatively comparable to NNs. Among the NNs, CNN performed best with an AUC of 92.28% ± 7.36%, ACC of 98.45% ± 1.72%, PPV of 96.62% ± 2.30%, NPV of 90.50% ± 11.92%, SR of 96.01% ± 3.09%, and RR of 89.21% ± 12.93%. In conclusion, NNs can be potentially used as a computational tool in lung cancer diagnosis based on infrared spectroscopy of lung tissues.

Serotype Identification of Human Adenoviruses Associated with Influenza-Like Illnesses in the Philippines from 2006-2012 by Microneutralization and Molecular Techniques.

OBJECTIVES: Human adenoviruses (HAdV) are known to cause a wide range of diseases including acute respiratory infections, conjunctivitis, and acute gastroenteritis. In this study, we aimed to determine the serotypes of HAdV in patients with influenza-like illness (ILI) in the Philippines from 2006-2012 and to describe the demographic and epidemiological characteristics of patients who tested positive for HAdV. METHODS: Between 2006 and 2012, the Philippine National Influenza Centre detected HAdV in 1294 samples of patients with ILI. Serotype determination was done in select samples using microneutralization, polymerase chain reaction (PCR), and sequencing methods. RESULTS: A total of 8 serotypes were identified (HAdV 1-7 and 11), with HAdV-2 (27.8%), and HAdV-3 (27.8%) being the most prevalent. The majority of HAdV infections were found in children below 5 years of age (79.9%). CONCLUSIONS: The identification of HAdV circulating serotypes may serve as guide for designing disease intervention and control strategies and will provide important information regarding the contribution of this virus to respiratory infections, particularly in children, which remain a public health burden in the Philippines.

Detection of breast cancer by ATR-FTIR spectroscopy using artificial neural networks.

In this study, three (3) neural networks (NN) were designed to discriminate between malignant (n = 78) and benign (n = 88) breast tumors using their respective attenuated total reflection Fourier transform infrared (ATR-FTIR) spectral data. A proposed NN-based sensitivity analysis was performed to determine the most significant IR regions that distinguished benign from malignant samples. The result of the NN-based sensitivity analysis was compared to the obtained results from FTIR visual peak identification. In training each NN models, a 10-fold cross validation was performed and the performance metrics-area under the curve (AUC), accuracy, positive predictive value (PPV), specificity rate (SR), negative predictive value (NPV), and recall rate (RR)-were averaged for comparison. The NN models were compared to six (6) machine learning models-logistic regression (LR), Naïve Bayes (NB), decision trees (DT), random forest (RF), support vector machine (SVM) and linear discriminant analysis (LDA)-for benchmarking. The NN models were able to outperform the LR, NB, DT, RF, and LDA for all metrics; while only surpassing the SVM in accuracy, NPV and SR. The best performance metric among the NN models was 90.48% ± 10.30% for AUC, 96.06% ± 7.07% for ACC, 92.18 ± 11.88% for PPV, 94.19 ± 10.57% for NPV, 89.04% ± 16.75% for SR, and 94.34% ± 10.54% for RR. Results from the proposed sensitivity analysis were consistent with the visual peak identification. However, unlike the FTIR visual peak identification method, the NN-based method identified the IR region associated with C-OH C-OH group carbohydrates as significant. IR regions associated with amino acids and amide proteins were also determined as possible sources of variability. In conclusion, results show that ATR-FTIR via NN is a potential diagnostic tool. This study also suggests a possible more specific method in determining relevant regions within a sample's spectrum using NN.

MicroRNA and Other Non-Coding RNAs in Epstein-Barr Virus-Associated Cancers.

EBV is a direct causative agent in around 1.5% of all cancers. The oncogenic properties of EBV are related to its ability to activate processes needed for cellular proliferation, survival, migration, and immune evasion. The EBV latency program is required for the immortalization of infected B cells and involves the expression of non-coding RNAs (ncRNAs), including viral microRNAs. These ncRNAs have different functions that contribute to virus persistence in the asymptomatic host and to the development of EBV-associated cancers. In this review, we discuss the function and potential clinical utility of EBV microRNAs and other ncRNAs in EBV-associated malignancies. This review is not intended to be comprehensive, but rather to provide examples of the importance of ncRNAs.

pks+ Escherichia coli more prevalent in benign than malignant colorectal tumors.

BACKGROUND: Some E. coli strains that synthesize the toxin colibactin within the 54-kb pks island are being implicated in colorectal cancer (CRC) development. Here, the prevalence of pks+ E. coli in malignant and benign colorectal tumors obtained from selected Filipino patients was compared to determine the association of pks+ E. coli with CRC in this population. METHODS AND RESULTS: A realtime qPCR protocol was developed to quantify uidA, clbB, clbN, and clbA genes in formalin fixed paraffin embedded colorectal tissues. The number of malignant tumors (44/62; 71%) positive for the uidA gene was not significantly different (p = 0.3428) from benign (38/62; 61%) tumors. Significantly higher number of benign samples (p < 0.05) were positive for all three colibactin genes (clbB, clbN, and clbA) compared with malignant samples. There was also higher prevalence of pks+ E. coli among older females and in tissue samples taken from the rectum. CONCLUSION: Hence, pks+ E. coli may not be associated with CRC development among Filipinos.

Discrimination of malignant from benign thyroid lesions through neural networks using FTIR signals obtained from tissues.

The current gold standard in cancer diagnosis-the microscopic examination of hematoxylin and eosin (H&E)-stained biopsies-is prone to bias since it greatly relies on visual examination. Hence, there is a need to develop a more sensitive and specific method for diagnosing cancer. Here, Fourier transform infrared (FTIR) spectroscopy of thyroid tumors (n = 164; 76 malignant, 88 benign) was performed and five (5) neural network (NN) models were designed to discriminate the obtained spectral data. PCA-LDA was used as classical benchmark for comparison. Each NN model was evaluated using a stratified 10-fold cross-validation method to avoid overfitting, and the performance metrics-accuracy, area under the curve (AUC), positive predictive value (PPV), negative predictive value (NPV), specificity rate (SR), and recall rate (RR)-were averaged for comparison. All NN models were able to perform excellently as classifiers, and all were able to surpass the LDA model in terms of accuracy. Among the NN models, the RNN model performed best, having an AUC of 95.29% ± 6.08%, an accuracy of 98.06% ± 2.87%, a PPV of 98.57% ± 4.52%, a NPV of 93.18% ± 7.93%, a SR value of 98.89% ± 3.51%, and a RR value of 91.25% ± 10.29%. The RNN model outperformed the LDA model for all metrics except for the AUC, NPV, and RR. In conclusion, NN-based tools were able to predict thyroid cancer based on infrared spectroscopy of tissues with a high level of diagnostic performance in comparison to the gold standard.

Clostridioides difficile antibody response of colorectal cancer patients versus clinically healthy individuals.

Dysbiosis, defined as an imbalance in the gut microbiota caused by too few beneficial bacteria and an overgrowth of bad bacteria, yeast, and/or parasites, is now being associated with several diseases, including the development of colorectal carcinoma (CRC). In this study, the potential association of Clostridioides difficile (formerly Clostridium difficile) with CRC was investigated. Plasma samples obtained from preoperative histologically confirmed CRC patients (n=39) and their age- and sex-matched clinically healthy controls (n=39) were analyzed for antibodies to toxin B of C. difficile (anti-tcdB) by enzyme-linked immunosorbent assay (ELISA). A significantly greater number (p=0.012) of CRC cases (n=26/39, 66.7%) had anti-tcdB IgG levels above the cutoff value compared with controls (n=12/39, 30.8%). Eight cases (8/39, 20.5%) and none of the controls registered anti-tcdB IgA levels above the cutoff value (p=0.0039). Anti-tcdB IgG and IgA levels were not shown to be significantly associated with tumor grade or tumor stage. Anti-tcdB IgG showed 66.7% sensitivity and 69.2% specificity. For anti-tcdB IgA, sensitivity and specificity were 20.5% and 100%, respectively. The positive predictive values for anti-tcdB IgA and IgG were 100% and 68.4%, respectively. The anti-tcdB IgA and IgG negative predictive values were 55.7% and 67.5%, respectively. The results suggest the potential association of C. difficile with CRC and anti-tcdB levels, particularly the IgA level. Hence, anti-tcdB antibodies can be candidate serologic markers for CRC.

ATR-FTIR spectroscopy as adjunct method to the microscopic examination of hematoxylin and eosin-stained tissues in diagnosing lung cancer.

Lung cancer remains the leading cause of cancer-related death worldwide. Since prognosis and treatment outcomes rely on fast and accurate diagnosis, there is a need for more cost-effective, sensitive, and specific method for lung cancer detection. Thus, this study aimed to determine the ability of ATR-FTIR in discriminating malignant from benign lung tissues and evaluate its concordance with H&E staining. Three (3) 5µm-thick sections were cut from formalin fixed paraffin embedded (FFPE) cell or tissue blocks from patients with lung lesions. The outer sections were H&E-stained and sent to two (2) pathologists to confirm the histopathologic diagnosis. The inner section was deparaffinized by standard xylene method and then subjected to ATR-FTIR analysis. Distinct spectral profiles that distinguished (p<0.05) one sample from another, called the "fingerprint region", were observed in five (5) peak patterns representing the amides, lipids, and nucleic acids. Principal component analysis and hierarchical cluster analysis evidently clustered the benign from malignant tissues. ATR-FTIR showed 97.73% sensitivity, 92.45% specificity, 94.85% accuracy, 91.49% positive predictive value and 98.00% negative predictive value in discriminating benign from malignant lung tissue. Further, strong agreement was observed between histopathologic readings and ATR-FTIR analysis. This study shows the potential of ATR-FTIR spectroscopy as a potential adjunct method to the gold standard, the microscopic examination of hematoxylin and eosin (H&E)-stained tissues, in diagnosing lung cancer.

Human Papillomavirus Serologic Profiles of Selected Filipinos with Head and Neck Squamous Cell Carcinoma.

BACKGROUND: The low prevalence of human papillomavirus (HPV) DNA and mRNA in biopsy samples of Filipinos with head and neck squamous cell carcinoma (HNSCC) has been reported previously. Here, the HPV serologic profiles of HNSCC cases were analyzed and associated with life-style and sexual practices. METHODS: Serum samples were collected between May 2012 and September 2013 from HNSCC patients (n = 22) in the northwest region of the Philippines, and age- and sex-matched clinically healthy controls. Antibodies to capsid and early oncoproteins of HPV16, 18, 31, 33, 45, 52, 58, 6, and 11 were analyzed using multiplex serology. RESULTS: Most of the cases were males with tumors of the oral cavity or larynx. Two of the cases tested positive for at least one of the early oncoproteins (E6, E7, E1, and/or E2) of HPV16, and 11 did not display reactivity to any HPV early or late oncoproteins. Of the controls, four tested positive for at least one of the HPV16 early oncoproteins, and 10 were non-reactive to all HPV types. Titers to HPV16 E6 or E7 of the seropositive cases and controls were considerably lower than those typically observed in economically developed countries. CONCLUSIONS: The low HPV titers seen here are consistent with the results of molecular analyses for this population. Hence, the seropositivity of some of the HNSCC cases is likely an indication of prior exposure to the virus and not the presence of HPV-driven tumors.

XRCC4 c.1394G>T Single Nucleotide Polymorphisms and Breast Cancer Risk among Filipinos

Background: The identification of cancer-associated single nucleotide polymorphisms (SNP) and mutation genes is a promising approach in recognizing individuals who are at risk of developing cancer. Hence, this study was conducted to determine the association between XRCC4 c.1394G>T SNP and breast cancer development among Filipinos. Methods: Genotyping for XRCC4 c.1394G>T SNP was performed on breast cancer patients (n=103) and their age- and sex- matched clinically healthy controls (n=103) by polymerase chain reaction ­ restriction fragment length polymorphism. Results: Significant difference in genotype (p=0.007) and allele (p=0.003) frequencies in XRCC4 c.1394G>T was observed between the breast cancer cases and controls. Carriers of the XRCC4 c.1394 G>T genotype were observed to have significantly higher risk of developing breast cancer compared to individuals with T/T genotype (OR=2.67, 95% CI: 1.36 ­ 5.25). XRCC4 c.1394G>T combined with passive smoking may also significantly increase risk of breast cancer (OR=14.73; 95% CI= 9.88-18.86). Conclusion: XRCC4 c. 1394G>T may be associated with breast cancer development among Filipinos.

GSTM1 and GSTT1 Genetic Polymorphisms and Breast Cancer Risk in Selected Filipino Cases

Background: The association of genetic polymorphisms with cancer development has been shown to be race- and tumor site-specific. Thus, this study aimed to determine whether polymorphisms in the GSTM1 and GSTT1 genes are associated with breast cancer among selected Filipinos. Methods: A total of 136 histologically confirmed breast cancer cases were age- and sex-matched with 136 clinically healthy controls. Genomic DNA extracted from blood samples of participants were screened for GSTM1 and GSTT1 genetic polymorphisms by multiplex PCR. Results: The frequency of null genotypes among the cases (GSTM1: n=78; 57.4%; GSTT1: n=61; 44.9%) was not significantly different (p>0.05) from the controls (GSTM1: n=93; 68.4%; GSTT1: n=59; 43.4%). It was also demonstrated that risk for breast cancer was increased in passive smokers carrying the GSTM1 null (OR=2.56; 95% CI=1.38-4.75) or GSTT1 positive (OR=2.00; 95% CI=1.05-3.83) genotypes. Moreover, risk was decreased in alcohol users carrying the GSTT1 null (OR=0.39; 95% CI=0.16-0.97) genotype. Conclusion: This study suggests that variants of GSTM1 and GSTT1 may not be risk factors for breast cancer development among Filipinos. However, the risk may be increased when these genotypes were combined with lifestyle or environmental factors.

Immunogenicity of a Fap2 peptide mimotope of Fusobacterium nucleatum and its potential use in the diagnosis of colorectal cancer.

BACKGROUND: The role of Fusobacterium nucleatum Fap2 protein in the development of colorectal cancer has recently been explained. Fap2, when bound to the human inhibitory receptor, TIGIT, inhibits the cytotoxic activity of natural killer (NK) cells against cancer cells, thus, allowing proliferation of the latter eventually leading to tumor growth. The aim of the study was to identify the immunogenicity of a peptide mimotope of the Fap2 protein and to determine the reactivity of colorectal cancer patients' sera against the mimotope. METHODS: Immunogenic epitope of the Fap2 protein of F. nucleatum was selected using the B-cell epitope prediction of the Immune Epitope Database and Analysis Resource (IEDB). The immunogenicity of the synthetic peptide mimotope of the Fap2 protein was determined in animal models and reactivity of colorectal cancer patients' sera against the mimotope was done by indirect ELISA. RESULTS: Results show that the selected peptide mimotope, with sequence TELAYKHYFGT, of the outer membrane protein Fap2 of F. nucleatum is immunogenic. Increase in the absorbance readings of peptide-immunized rabbit sera was observed starting Week 1 which was sustained up to Week 10 in the indirect ELISA performed. Colorectal cancer cases (n = 37) were all reactive in an ELISA-based analysis using the mimotope as the capture antigen. CONCLUSIONS: In this study, we identified an immunogenic epitope of the Fap2 protein of the Fusobacterium nucleatum. We demonstrated the reactivity of serum of histopathologically confirmed CRC patients in a peptide-capture indirect ELISA which may serve as proof of concept for the development of CRC diagnostics.

Low prevalence of human papillomavirus in head and neck squamous cell carcinoma in the northwest region of the Philippines.

BACKGROUND: Geographic heterogeneity of human papillomavirus (HPV) involvement in head and neck squamous cell carcinoma (HNSCC) has been observed over the last few years. This trend has not been evaluated in the Philippines. Hence, this study aims to provide for the first time a data on the prevalence of HPV in HNSCC in the northwestern region of the Philippines. METHODS: Two hundred one (201) biopsy samples (179 formalin fixed paraffin embedded and 22 fresh frozen) from 163 Filipino HNSCC cases (oral cavity = 88; larynx = 60; oropharynx = 15) diagnosed between 2003 to 2013 were initially included in this study. HPV DNA was detected by two methods: (1) BSGP5+/6+-PCR/ multiplex human papillomavirus genotyping and (2) TaqMan probes-based real-time qPCR. Presence of HPV type-specific transcripts were also analyzed by reverse transcription-PCR with subsequent hybridization to oligonucleotide probes coupled to Luminex beads. Co-amplification of the ß-globin and ubiquitin C genes served as internal positive controls for DNA and RNA analyses, respectively. RESULTS AND CONCLUSIONS: Of the 163, 82 (50.3%) cases had at least one tissue sample that was valid for molecular analysis. Only two of the DNA valid cases (2.4%) were HPV DNA-positive (HPV11 and HPV33). All HPV mRNA assays rendered negative results except for HPV11 transcripts. Results of this study may indicate that there is probably very low prevalence of HPV-associated HNSCC among Filipino adults living in a rural region of the Philippines. This study could serve as a benchmark for designing follow-up studies that would assess possible changes in trends of HNSCC among Filipinos in different ethnic regions of the country, especially urban areas in which the population is expected to adapt Western style sexual behavior. A prospective sampling of fresh frozen tissue is also highly recommended to ensure better molecular analyses.

Overall survival of Filipino patients with squamous cell carcinoma of the head and neck: a single-institution experience.

This paper is the first to present the incidence and overall survival of patients with squamous cell carcinoma of the head and neck (SCCHN) from the extreme northern part of the Philippines. We retrospectively retrieved the records of patients with histologically-confirmed squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx and larynx at the Mariano Marcos Memorial Hospital and Medical Center, Ilocos Norte, Philippines, from 2003 to 2012 and analysed prognostic factors associated with survival. Of the 150 cases, only 80 (53.3%) were still living when the study was terminated. Median age at initial diagnosis was 61.5 years and the male to female ratio was 7:3. The majority of the cases had tumours in the oral cavity (50.7%), followed by the larynx (36.7%). Sex (log rank=1.94, p value/α=0.16), tumor site (log rank=0.02, p value/α=0.90), tumor grade (log rank=1.74, p value/α=0.42), and node stage (log rank=0.07, p value/α=0.80) were not shown to be associated with the survival of our cases. Only 45 (30.0%) had no regional lymph node involvement (N0) at presentation and 12 (8.0%) had already developed distant metastases. Among the 150 patients, 71 (47.3%) were not able to receive treatment of any kind. Oddly, treatment (log rank=1.65, p value/α=0.20) was also shown to be not associated with survival. The survival rate of those who underwent surgery, radiotherapy, or both was not statistically different from those who did not receive any treatment. Only the tumor stage (log rank=4.51, p value/α=0.03) was associated with patient survival. The overall mean survival was 49.3 months, with survival rate diminishing from 88.3% during the 1st year to 1.80% by end of the study. This relatively low survival rate of our cases only reflects their poor access to quality diagnostic and treatment facilities.