Incidence Of Human Cancer Research Articles

Trichloroethylene: An Update on an Environmental Contaminant with Multiple Health Effects.

The halogenated solvent trichloroethylene (TCE) has had many uses in medicine, construction, consumer products, and the military. Many of these uses have been discontinued or restricted due to its toxicity, which affects multiple target organs and includes both acute, high-dose toxicity and chronic, low-dose toxicity that also encompass several cancers. US and international agencies have conducted risk and hazard assessments for TCE, with comprehensive publications coming out in the last 10-15 years. Accordingly, the focus of this article is to review recently published data since that time (i.e., 2014) that clarify unsettled questions or provide additional insights into the metabolism and mechanisms of toxicity of TCE in several target organs. Besides metabolism, the review focuses on the kidneys, liver, immune system, nervous system, cardiovascular and pulmonary systems, the search for biomarkers, and recent analyses of human cancer risk and incidence from TCE exposure.

Tracking Interprovincial Flows of Atmospheric PAH Emissions Through Downscaling Estimates With Province‐Specific Emission Factors

AbstractAtmospheric polycyclic aromatic hydrocarbons (PAHs), which are emitted significantly by economic sectors, are closely related to the global incidence of human cancer. When assessing temporal changes in PAH emissions in a country that is vast in area, such as China, it is crucial to consider socioeconomic differences across geological regions. In this study, we developed PAH emission factors at the provincial level and used them to compile a Chinese PAH emission inventory. Subsequently, we estimated trade‐driven PAH emissions at the provincial level in 2007, 2010, 2012, 2015, and 2017, and examined the critical supply chain paths. The updated inventory reveals a distinct temporal trend in trade‐driven PAH emissions, although they remain at an order of magnitude similar to previous estimates. National total production‐, consumption‐, and income‐based PAH emissions, despite a rebound in 2012, exhibit a general decline from 59.3, 43.3, and 48.8 kt in 2007 to 52.1, 43.9, and 47.0 kt in 2017, respectively. These declines align with economic adjustments and emissions mitigation legislation. Spatial hotspots were concentrated in the most affluent Yangtze River Delta, Pearl River Delta, and Jing‐Jin‐Ji provinces on the demand side and in the northern coal resource‐rich provinces on the supply side. They primarily drive PAH emissions from the heavy industrial sectors of northern coal resource‐rich provinces. Fewer affluent provinces have experienced a rapid increase in trade‐driven PAH emissions after 2012, emphasizing the need for synergistic reduction measures to combat PAH pollution.

Thyroid disease-related sleep disorders and its diagnostic and therapeutic recommendations: A literature review

As perioperative medicine evolves, more hospitals are offering comfort sleep clinics. Thyroid disorders (e.g., hypothyroidism, hyperthyroidism, and thyroid cancer) affect the peripheral circadian clock. Elevated serum thyroid-stimulating hormone levels have been found to associate with the incidence of thyroid cancer in humans, but the relationship between circadian disruption and thyroid disease requires further investigation. Malignant transformation of thyroid nodules is characterized by disruption of the expression of biological clock genes. Sleep clinics often see patients complaining of sleepiness and tinnitus. These patients often have comorbid thyroid disorders and are therefore highly susceptible to misdiagnosis or underdiagnosis. In this article, we first summarize this category of disorders, which we propose to classify as insomnia secondary to somatic disease and define as thyroid disease-related sleep disorder (TSD). The primary and common clinical complaints of TSD patients are different types of sleep disorders. In addition, we attempt to provide some preliminary diagnostic and therapeutic recommendations for TSD in the hope that it may assist healthcare professionals in the early diagnosis and management of this disorder.

The GLP-1 receptor is expressed in vivo by human metastatic prostate cancer.

The glucagon-like peptide-1 (GLP-1) receptor agonist, liraglutide, reduces human prostate cancer incidence, and similar GLP-1 receptor agonists reduce in vitro proliferation and in vivo growth of prostate cancer cell lines. Primary human prostate cancer expresses the GLP-1 receptor (GLP-1R) in vitro. Cancer evolves with stage, and whether advanced-stage human prostate cancer expresses GLP-1R is unknown. We hypothesised and aimed to prove that human metastatic castrate-resistant prostate cancer (mCRPC) expresses the GLP-1R in vivo. We hypothesised that mCRPC would thus be detectable by positron emission tomography/computed tomography (PET/CT) using a radiotracer bound to a GLP-1R ligand, as in exendin PET/CT. Men with mCRPC, with more than one prostate-specific membrane antigen (PSMA)-avid lesion on PET/CT scanning (pathognomic in that setting for prostate cancer lesions), were approached to undergo PET/CT with gallium68-Dota-exendin-4. We documented PET/CT PSMA-avid lesions, which were also PET/CT exendin avid, as evidence of in vivo GLP-1R expression. Out of the 24 men referred, three did not meet the inclusion criteria. Seventeen declined, largely because the study offered them no therapeutic benefit. Among the four men imaged, three had no exendin-avid lesions, while one had six osseous PSMA-avid lesions, three of which were also exendin avid. We demonstrated in vivo GLP-1R expression by human mCPRC, detecting PET/CT lesions avid for both PSMA and exendin, in one of four participants. GLP-1R expression may thus occur even in advanced-stage prostate cancer. Our data contribute to growing evidence supporting the testing of GLP-1 receptor agonists for therapeutic benefit in prostate cancer.

The impact of food availability on tumorigenesis is evolutionarily conserved

The inability to control cell proliferation results in the formation of tumors in many multicellular lineages. Nonetheless, little is known about the extent of conservation of the biological traits and ecological factors that promote or inhibit tumorigenesis across the metazoan tree. Particularly, changes in food availability have been linked to increased cancer incidence in humans, as an outcome of evolutionary mismatch. Here, we apply evolutionary oncology principles to test whether food availability, regardless of the multicellular lineage considered, has an impact on tumorigenesis. We used two phylogenetically unrelated model systems, the cnidarian Hydra oligactis and the fish Danio rerio, to investigate the impact of resource availability on tumor occurrence and progression. Individuals from healthy and tumor-prone lines were placed on four diets that differed in feeding frequency and quantity. For both models, frequent overfeeding favored tumor emergence, while lean diets appeared more protective. In terms of tumor progression, high food availability promoted it, whereas low resources controlled it, but without having a curative effect. We discuss our results in light of current ideas about the possible conservation of basic processes governing cancer in metazoans (including ancestral life history trade-offs at the cell level) and in the framework of evolutionary medicine.

Lipid accumulation-mediated histone hypoacetylation drives persistent NK cell dysfunction in anti-tumor immunity

Hyperlipidemia impairs anti-tumor immune responses and is closely associated with increased human cancer incidence and mortality. However, the underlying mechanisms are not well understood. In the present study, we show that natural killer (NK) cells isolated from high-fat-diet mice or treated with oleic acid (OA) invitro exhibit sustainable functional defects even after removal from hyperlipidemic milieu. This is accompanied by reduced chromatin accessibility in the promoter region of NK cell effector molecules. Mechanistically, OA exposure blunts P300-mediated c-Myc acetylation and shortens its protein half-life in NK cells, which in turn reduces P300 accumulation and H3K27 acetylation and leads to persistent NK cell dysfunction. NK cells engineered with hyperacetylated c-Myc mutants surmount the suppressive effect of hyperlipidemia and display superior anti-tumor activity. Our findings reveal the persistent dysfunction of NK cells in dyslipidemia milieu and extend engineered NK cells as a promising strategy for tumor immunotherapy.

A Poisson distribution-based general model of cancer rates and a cancer risk-dependent theory of aging.

This article presents a formula for modeling the lifetime incidence of cancer in humans. The formula utilizes a Poisson distribution-based "np" model to predict cancer incidence, with "n" representing the effective number of cell turnover and "p" representing the probability of single-cell transformation. The model accurately predicts the observed incidence of cancer in humans when a reduction in cell turnover due to aging is taken into account. The model also suggests that cancer development is ultimately inevitable. The article proposes a theory of aging based on this concept, called the "np" theory. According to this theory, an organism maintains its order by balancing cellular entropy through continuous proliferation. However, cellular "information entropy" in the form of accumulated DNA mutations increases irreversibly over time, restricting the total number of cells an organism can generate throughout its lifetime. When cell division slows down and fails to compensate for the increased entropy in the system, aging occurs. Essentially, aging is the phenomenon of running out of predetermined cell resources. Different species have evolved separate strategies to utilize their limited cell resources throughout their life cycle.

Exploring the presence of bovine leukemia virus among breast cancer tumors in a rural state.

The bovine leukemia virus (BLV) is a deltaretrovirus that causes malignant lymphoma and lymphosarcomas in cattle globally and has high prevalence among large scale U.S. dairy herds. Associations between presence of BLV DNA in human mammary tissue and human breast cancer incidence have been reported. We sought to estimate the prevalence of BLV DNA in breast cancer tissue samples in a rural state with an active dairy industry. We purified genomic DNA from 56 fresh-frozen breast cancer tissue samples (51 tumor samples, 5 samples representing adjacent normal breast tissue) banked between 2016 and 2019. Using nested PCR assays, multiple BLV tax sequence primers and primers for the long terminal repeat (LTR) were used to detect BLV DNA in tissue samples and known positive control samples, including the permanently infected fetal lamb kidney cell line (FLK-BLV) and blood from BLV positive cattle. The median age of patients from which samples were obtained at the time of treatment was 60 (40-93) and all were female. Ninety percent of patients had invasive ductal carcinoma. The majority were poorly differentiated (60%). On PCR assay, none of the tumor samples tested positive for BLV DNA, despite having consistent signals in positive controls. We did not find BLV DNA in fresh-frozen breast cancer tumors from patients presenting to a hospital in Vermont. Our findings suggest a low prevalence of BLV in our patient population and a need to reevaluate the association between BLV and human breast cancer.

Global burden and trends of lung cancer incidence and mortality.

Lung cancer has been the leading cause of cancer-related deaths worldwide for many years. This study aimed to investigate the global patterns and trends of lung cancer. Lung cancer incidence and mortality were derived from the GLOBOCAN 2020 database. Continuous data from Cancer Incidence in Five Continents Time Trends were used to analyze the temporal trends from 2000 to 2012 using Joinpoint regression, and average annual percent changes were calculated. The association between the Human Development Index and lung cancer incidence and mortality was assessed by linear regression. An estimated 2.2 million new lung cancer cases and 1.8 million lung cancer-related deaths occurred in 2020. The age-standardized incidence rate (ASIR) ranged from 36.8 per 100,000 in Demark to 5.9 per 100,000 in Mexico. The age-standardized mortality rate (ASMR) varied from 32.8 per 100,000 in Poland to 4.9 per 100,000 in Mexico. Both ASIR and ASMR were approximately twice higher in men than in women. The ASIR of lung cancer showed a downward trend in the United States of America (USA) between 2000 and 2012, and was more prominent in men. The age-specific incidence rates of lung cancer for ages of 50 to 59 years showed an upward trend in China for both men and women. The burden of lung cancer is still unsatisfactory, especially in developing countries like China. Considering the effectiveness of tobacco control and screening in developed countries, such as the USA, there is a need to strengthen health education, accelerate the establishment of tobacco control policies and regulations, and improve early cancer screening awareness to reduce the future burden of lung cancer.

Vitamin D and Diagnostic Colonoscopy for Colorectal Cancer in Indonesian Population: A Cross-sectional Study

BACKGROUND: Colorectal cancer (CRC) is the world’s third most common type of cancer. Case studies have shown an inverse correlation between serum Vitamin D levels and the incidence of human colorectal cancer. AIM: This study aims to assess Vitamin D levels in patients who underwent colonoscopy for diagnostic colorectal cancer. METHODS: This research is a cross-sectional study. This study’s subjects were patients who visited the Digestive Surgery polyclinic and underwent a colonoscopy to diagnose colorectal cancer. Level of Vitamin D was collected before the colonoscopy examination and categorized into three groups: Vitamin D with a value of < 20 ng/mL indicates a deficiency, a level of 20–30 ng/mL as an insufficiency level, and a value > 30 ng/mL as a sufficient value. A colonoscopy examination was performed to obtain a diagnosis of colorectal cancer based on anatomical pathology examination. RESULTS: Examination of Vitamin D levels from 120 subjects showed that the average vitamin level was 16.36 ng/mL, which indicates Vitamin D deficiency levels. A total of 85 (70.8%) subjects showed Vitamin D deficiency, as many as 24 (20%) showed Vitamin D insufficiency levels, and only 11 (9.2%) study subjects showed sufficient Vitamin D levels. The colonoscopy showed 60 (50%) subjects with colorectal cancer. The relationship between Vitamin D levels and the diagnosis of CRC showed a value of p = 0.60 (p > 0.05). CONCLUSION: There is no significant difference between low levels of Vitamin D and the diagnosis of colorectal cancer patients.

The Anti-Tumorigenic Role of Cannabinoid Receptor 2 in Colon Cancer: A Study in Mice and Humans.

The endocannabinoid system, particularly cannabinoid receptor 2 (CB2 in mice and CNR2 in humans), has controversial pathophysiological implications in colon cancer. Here, we investigate the role of CB2 in potentiating the immune response in colon cancer in mice and determine the influence of CNR2 variants in humans. Comparing wild-type (WT) mice to CB2 knockout (CB2-/-) mice, we performed a spontaneous cancer study in aging mice and subsequently used the AOM/DSS model of colitis-associated colorectal cancer and a model for hereditary colon cancer (ApcMin/+). Additionally, we analyzed genomic data in a large human population to determine the relationship between CNR2 variants and colon cancer incidence. Aging CB2-/- mice exhibited a higher incidence of spontaneous precancerous lesions in the colon compared to WT controls. The AOM/DSS-treated CB2-/- and ApcMin/+CB2-/- mice experienced aggravated tumorigenesis and enhanced splenic populations of immunosuppressive myeloid-derived suppressor cells along with abated anti-tumor CD8+ T cells. Importantly, corroborative genomic data reveal a significant association between non-synonymous variants of CNR2 and the incidence of colon cancer in humans. Taken together, the results suggest that endogenous CB2 activation suppresses colon tumorigenesis by shifting the balance towards anti-tumor immune cells in mice and thus portray the prognostic value of CNR2 variants for colon cancer patients.

HPV-related oropharyngeal cancer: identifying and quantifying topics of patient interest.

As the incidence of human papillomavirus related oropharyngeal cancer continues to rise, it is increasingly important for public understanding to keep pace. This study aimed to identify areas of patient interest and concern regarding human papillomavirus and oropharyngeal cancer. This study was a retrospective survey of search queries containing the keywords 'HPV cancer' between September 2015 and March 2021. There was 3.5-fold more interest in human papillomavirus related oropharyngeal cancer (15 800 searches per month) compared with human papillomavirus related cervical cancer (4500 searches per month). Among searches referencing cancer appearance, 96.8 per cent pertained to the head and neck region (3050 searches per month). Among vaccination searches, 16 of 47 (34.0 per cent; 600 searches per month) referenced human papillomavirus vaccines as being a cause of cancer rather than preventing cancer. The vast majority of online searches into human papillomavirus cancer pertain to the oropharynx. There are relatively few search queries on the topic of vaccination preventing human papillomavirus associated oropharyngeal cancer, which highlights the continued importance of patient education and awareness campaigns.

Potentiation of Cell Death and DNA Damage Through 5-Fluorouracil and Ferulic Acid Coadministration in p53 Mutant HT-29 Cell Lines

When the Mediterranean diet is set in focus, scientific studies report a strong statistical correlation between human nutrition, diet, and cancer incidence. Considering the anticancer effects of a fiber-rich diet, it is understood that the anticancer effect is not only due to the bulk cellulosic material load but also related to the increased bioavailability of cellulose-bound bioactive (anticancer) compounds released due to intestinal microfloral activities. Ferulic acid (FA) is one of the components found ubiquitously in the fiber fraction of plant food. Because of its effects on cancer cell viability and its association with a low incidence of cancer concerning a high-fiber diet, FA can be considered an anticancer agent. Here in this work, it was investigated whether FA can potentiate the effects of anticancer drugs at lower doses. For this, a general anticancer drug named 5-Fluorouracil (5-FU) was used, and potentiation tests were performed on two cancer cell lines, namely A2780 besides HT-29, which has the homozygous mutation for p53. The results are interpreted as follows: anticancer effect of 5-FU was readily potentiated with 200 µM of FA in both cancer cell lines, and DNA damage-induced with 5-FU was enhanced with co-administration of FA. When cell viability and DNA damage of A2780 and HT-29 lines are evaluated together, we think it is most probable that 5-FU and FA administered jointly show its anticancer effect, especially by strengthening the apoptosis pathway triggered by DNA damage. 
 If it might be possible to uncover the mechanism that drove DNA damage mediated apoptosis in p53 mutant HT-29 cells in our work we may shed light on the treatment of chemotherapy-resistant cancer incidences.

The Regulatory Mechanism of miR-574-5p Expression in Cancer.

MicroRNAs (miRNAs) are a group of small, single-stranded, non-coding RNAs approximately 22 nucleotides in length. The dysregulation of miRNAs has been widely investigated in various pathological processes, including tumorigenesis, providing a biomarker for cancer diagnosis and prognosis. As a member of the miRNA family, miR-574-5p is located on the human chromosome 4p14 and is highly correlated with a high incidence of human cancers. Functional pathways as well as underlying novel mechanisms upregulate or downregulate miR-574-5p, which plays an important regulatory role in tumorigenesis and progression. In this review, we systematically summarize the context-dependent implications of miR-574-5p and review differences in miR-574-5p expression in cancer. We also investigate the intricate functions exerted by miR-574-5p in diverse pathological processes and highlight regulatory pathways, networks, and other underlying novel mechanisms. The clinical applications of miR-574-5p as a diagnostic biomarker, prognostic biomarker, and therapeutic mechanism are also discussed in this paper. On this basis, we anticipate that miR-574-5p will be a promising and effective biomarker and therapeutic target.

Factors Related to Human Papillomavirus Positivity among Oral Cavity and Pharynx Cancers from Surveillance, Epidemiology and End Results (SEER) Program Data.

As human papillomavirus positive (HPV+) oral cavity and pharynx cancer (OCPC) incidence increases significantly, our objective was to determine whether selected sociodemographic and clinical factors were associated with HPV+ OCPCs overall and by oropharyngeal and non-oropharyngeal sites. Surveillance, Epidemiology and End Results (SEER) Program data were used in this study. Specifically, univariate and logistic regression models were used to examine the relationships between HPV+ and HPV- OCPC cases and age, sex, race, ethnicity, marital status, factors of neighborhood socioeconomic status (i.e., nSES/Yost index) and rurality/urbanity, first malignancy status, histology, reporting source, stage at diagnosis, and OCPC anatomic site. The same approach was used to identify risk factors for HPV positivity for oropharyngeal and non-oropharyngeal OCPCs separately. In all OCPCs, cases that were male, <80 years old, lived in the four highest nSES categories, diagnosed with a non-"gum and other mouth" OCPC (ref = hypopharynx), not locally staged at diagnosis, and a first malignancy had higher odds of being HPV+. Cases that were American Indian/Alaska Native and Asian or Pacific Islander (ref = White), Spanish-Hispanic-Latino ethnicity, non-married/partnered, and not reported by a hospital/clinic had lower odds of being HPV+. Associations were maintained in oropharyngeal OCPCs and only age and race remained significant for non-oropharyngeal OCPCs. Sociodemographic and clinical differences in HPV+ and HPV- OCPC, overall and for (non)oropharyngeal, cases exist. Identification of OCPC and (non)oropharyngeal risk factors for HPV positivity may assist in discovering high-risk groups that should receive enhanced public health efforts to reduce the U.S. OCPC burden.

Oncologic necessity for the complete removal of residual microcalcifications after neoadjuvant chemotherapy for breast cancer

The surgical range of breast cancer that shows pathologic complete response (pCR) without change in microcalcifications after neoadjuvant chemotherapy (NAC) is controversial. This study examined whole breast specimens to evaluate the necessity of mastectomy in those cases. The viability of cancer cells around the residual microcalcification was assessed using prospectively collected breast samples to confirm the presence or absence of cancer cells. A total of 144 patients with breast cancer and diffuse microcalcifications were classified into the reduced mass with no change in residual microcalcification (RESMIN, n = 49) and non-RESMIN (n = 95) groups. Five specimens were prospectively evaluated to assess the presence of viable cancer cells around the microcalcification. Tumor responses to NAC were significantly better with high pCR rates in the RESMIN group (p = 0.005 and p = 0.002). The incidence of human epidermal growth factor receptor 2-positive and triple-negative breast cancers was significantly high in the RESMIN group (p = 0.007). Although five (10.2%) patients had locoregional recurrence in the RESMIN group, no local recurrence in the breast was reported. Although pCR was highly estimated, residual cancers, including ductal carcinoma in situ, remained in 80% cases. Therefore, given the weak scientific evidence available currently, complete removal of residual microcalcifications should be considered for oncologic safety.

Trypanosoma cruzi-Derived Molecules Induce Anti-Tumour Protection by Favouring Both Innate and Adaptive Immune Responses

Lung cancer remains the leading cause of cancer mortality worldwide. Thus, the development of strategies against this type of cancer is of high value. Parasite infections can correlate with lower cancer incidence in humans and their use as vaccines has been recently explored in preclinical models. In this study, we investigated whether immunisations with a Trypanosoma cruzi lysate from epimastigotes protect from lung tumour growth in mice. We also explore the role of parasite glycans in the induction of the protective immune response. A pre-clinical murine cancer model using the lung tumour cell line LL/2 was used to evaluate the anti-tumour potential, both in preventive and therapeutic settings, of a T. cruzi epimastigote-derived protein lysate. Immunisation with the parasite lysate prevents tumour growth and induces both humoral and cellular anti-tumour immune responses to LL-2 cancer cells. The induced immunity and tumour protection were associated with the activation of natural killer (NK) cells, the production of interferon-γ (IFN-γ) and tumour cell cytotoxicity. We also show that mannose residues in the T. cruzi lysate induce Toll-like receptor (TLR) signalling. The evaluated T. cruzi lysate possesses anti-tumour properties likely by activating innate and adaptive immunity in a process where carbohydrates seem to be essential.

Potential role of long noncoding RNA RP5-881L22.5 as a novel biomarker and therapeutic target of colorectal cancer.

The incidence of colorectal cancer in humans is high, and it is in the top five for cancer-related morbidity and mortality. It is one of the main threats to human health. The function of long noncoding RNAs in tumor occurrence and development has gradually gained attention in recent years. In increasing numbers of studies, researchers have demonstrated that it plays an important role in the pathogenesis of colorectal cancer. To find out if long noncoding RNA RP5-881L22.5 played a role in the pathogenesis of colorectal cancer in relation to the tumor microenvironment. We analyzed the transcriptome data and clinical data in The Cancer Genome Atlas-colon adenocarcinoma. The CIRBERSORT algorithm was applied to evaluate these tumor-infiltrating immune cells in The Cancer Genome Atlas-colon adenocarcinoma cancer tissue samples. Using the "estimate" package in R, we assessed the tumor immune microenvironment. The expression level of RP5-881L22.5 in tumor tissue and adjacent normal tissue samples from 4 pairs of colorectal cancer patients was determined by quantitative reverse transcription PCR. Colorectal cancer cells were tested for invasiveness using a transwell invasion assay after RP5-881L22.5 expression was knocked down. The expression of lncRNA RP5-881L22.5 was related to the clinical characteristics of the tumors, and it was negatively related to the infiltration level of immune cells in the tumor microenvironment and the expression of T cell inhibitory receptors. A major function of its coexpressed mRNA was to regulate tumor immunity, such as the immune response. When quantitative reverse transcription PCR was performed on tumor tissues from 4 pairs of colorectal cancer patients, the results showed that RP5-881L22.5 was highly expressed. Subsequently, knocking down the expression of RP5-881L22.5, the invasiveness of colorectal cancer cell lines was reduced, and the apoptosis rate was increased. RP5-881L22.5 plays a crucial role in the microenvironment of tumors as well as in the pathogenesis of colorectal cancer. The relationship between RP5-881L22.5 and the tumor immune microenvironment deserves further study.

Incidence and Characteristics of Human Papillomavirus-Positive Oropharyngeal Cancers by p16 Expression

Background: Head-and-neck cancers are one of the most common cancers in the Indian subcontinent. The rising incidence of human papillomavirus (HPV), especially in oropharyngeal cancers is likely to increase the burden by many folds. Hence, we decided to study the incidence of HPV in oropharyngeal carcinoma and its characteristics. Materials and Methods: Patients with primary squamous cell carcinoma (SCC) of the oropharynx registered in our hospital between September 2018 and July 2020 were included in the study after obtaining informed consent. A total of 60 patients were included in the study. The evaluation of HPV status was done by immunohistochemistry for p16 expression. Results: The median age of presentation was 60 years (range: 38–85 years). Fifty-four patients were male and six patients were female. The incidence of HPV in oropharyngeal carcinoma was 21.7% (n = 13). There was no difference seen when we compare HPV-positive patients with HPV-negative patients as well as with the entire study population for the demographic characteristics such as age (P = 0.569), gender (P = 0.754), smoker (P = 0.368), history of alcohol consumption (P = 0.558), and history of tobacco chewing (P = 0.781). We did not find any association between HPV-positive and HPV-negative patients with anatomical subsites (P = 0.369), tumor stage (P = 0.397), and nodal stage (P = 0.592). HPV-positive oropharyngeal SCC (OPSCC) patients presented more at early stage as compared to HPV-negative patients (P = 0.005). HPV-positive patients had higher incidence of histological poor differentiation than HPV-negative patients (P = 0.024). Conclusion: The study highlighted the incidence of HPV (21.7%) among OPSCC patients using p16 expression. HPV-positive patients have propensity for early stage of presentation and histological poor differentiation. The demographic characteristics and anatomical subsites of OPSCC had no impact on HPV status.

LBA1 Mechanism of action and an actionable inflammatory axis for air pollution induced non-small cell lung cancer: Towards molecular cancer prevention

A mechanistic basis for non-small cell lung cancer (NSCLC) initiation in never smokers, a disease with a high frequency of EGFR mutations (EGFRm), is unknown. The air pollutant, particulate matter (PM), is known to be associated with the risk of NSCLC, however a direct cause and mechanism remain elusive. We analysed 463,679 individuals to address the associations of increasing 2.5um PM (PM2.5) concentrations with cancer risk. We performed ultra-deep profiling of 247 normal lung tissue samples, analysed normal lung tissue from humans and mice following exposures to PM, and investigated the consequences of PM on tumour promotion in mouse lung cancer models. Increasing PM2.5 levels were associated with increased risk of EGFRm NSCLC in England, S.Korea and Taiwan and with increased risk of mesothelioma (HR=1.19), lung (HR=1.16), anal (HR=1.23), small intestine (HR=1.30), GBM (HR=1.19), lip, oral cavity and pharynx (HR: 1.15) and laryngeal carcinomas (HR=1.26) in UK Biobank; HR for each 1ug/m3 PM2.5 increment. 18-33% of normal lung tissue samples harbour driver mutations in EGFR and KRAS in the absence of malignancy. PM promotes a macrophage response and a progenitor-like state in lung epithelium harbouring mutant EGFR. Consistent with PM promoting NSCLC in at-risk epithelium harbouring driver mutations, PM increased tumour burden in three EGFR or KRAS driven lung cancer models in a dose-dependent manner. Finally, we uncover an actionable inflammatory axis driven by IL1B in response to PM, with anti-IL1B therapy preventing PM-induced mouse tumour formation, consistent with reductions in human lung cancer incidence with anti-IL1B therapy. These results shed light on the aetiology of EGFRm lung cancer, particularly in never-smokers, and suggest that oncogenic mutations may be necessary but insufficient for tumour formation. These data reveal a mechanistic basis for PM driven lung cancer in the absence of classical carcinogen-driven mutagenesis, reminiscent of models of tumour initiation and promotion proposed 70 years ago, providing evidence to limit air pollution and opportunities for molecular targeted cancer prevention.