The rapidly rising incidence of papillary thyroid cancer may be due to overdiagnosis of a reservoir of subclinical disease. To conclude that overdiagnosis is occurring, evidence for an association ...between access to health care and the incidence of cancer is necessary.
We used Surveillance, Epidemiology, and End Results (SEER) data to examine U.S. papillary thyroid cancer incidence trends in Medicare-age and non-Medicare-age cohorts over three decades. We performed an ecologic analysis across 497 U.S. counties, examining the association of nine county-level socioeconomic markers of health care access and the incidence of papillary thyroid cancer.
Papillary thyroid cancer incidence is rising most rapidly in Americans over age 65 years (annual percentage change, 8.8%), who have broad health insurance coverage through Medicare. Among those under 65, in whom health insurance coverage is not universal, the rate of increase has been slower (annual percentage change, 6.4%). Over three decades, the mortality rate from thyroid cancer has not changed. Across U.S. counties, incidence ranged widely, from 0 to 29.7 per 100,000. County papillary thyroid cancer incidence was significantly correlated with all nine sociodemographic markers of health care access: it was positively correlated with rates of college education, white-collar employment, and family income; and negatively correlated with the percentage of residents who were uninsured, in poverty, unemployed, of nonwhite ethnicity, non-English speaking, and lacking high school education.
Markers for higher levels of health care access, both sociodemographic and age-based, are associated with higher papillary thyroid cancer incidence rates. More papillary thyroid cancers are diagnosed among populations with wider access to healthcare. Despite the threefold increase in incidence over three decades, the mortality rate remains unchanged. Together with the large subclinical reservoir of occult papillary thyroid cancers, these data provide supportive evidence for the widespread overdiagnosis of this entity.
Recent advancements in the field of immunotherapy have yielded encouraging results for the treatment of advanced cancers. Cyclic dinucleotides (CDNs) are a powerful new class of immunotherapy drugs ...known as STING (Stimulator of Interferon Genes) agonists, currently in clinical trials. However, previous studies of CDNs in murine cancer models have required multiple injections, and improve survival only in relatively nonaggressive tumor models. Therefore, we sought to improve the efficacy of CDN immunotherapy by developing a novel biomaterial we call “STINGel.” STINGel is an injectable peptide hydrogel that localizes and provides controlled release of CDN delivery, showing an 8-fold slower release rate compared to a standard collagen hydrogel. The carrier hydrogel is a positively charged, MultiDomain Peptide (MDP) which self-assembles to form a nanofibrous matrix and is easily delivered by syringe. The highly localized delivery of CDN from this nanostructured biomaterial affects the local histological response in a subcutaneous model, and dramatically improves overall survival in a challenging murine model of head and neck cancer compared to CDN alone or CDN delivered from a collagen hydrogel. This study demonstrates the feasibility of biomaterial-based immunotherapy platforms like STINGel as strategies for increasing the efficacy of CDN immunotherapies.
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Chemoradiation therapy has become increasingly popular in the treatment of advanced laryngeal cancer as part of an organ preservation protocol. However, several studies have reported a decline in ...survival, possibly attributable to the increased use of radiation and chemoradiation therapy.
To evaluate survival outcomes of laryngeal conservation vs surgical therapy in the treatment of advanced laryngeal cancer in the United States using a large population-based cancer database.
Population-based, nonconcurrent cohort study of 5394 patients who received a diagnosis of stage III or IV laryngeal squamous cell carcinoma between 1992 and 2009. Data were extracted from the Surveillance, Epidemiology, and End Results 18 Database.
Surgical or nonsurgical therapy.
Overall survival (OS) and disease-specific survival (DSS).
Patients who received surgical therapy had better 2-year and 5-year DSS (70% vs 64% and 55% vs 51%, respectively; P < .001) and 2-year and 5-year OS (64% vs 57% and 44% vs 39%, respectively; P < .001) than patients who received nonsurgical therapy. The difference in DSS and OS between treatment groups remained after stratification by year-of-diagnosis cohorts (P < .001). The survival gap consistently narrowed with subsequent year-of-diagnosis cohorts. On multivariable analysis, nonsurgical patients had worse DSS (hazard ratio HR, 1.33 95% CI, 1.21-1.45) and OS (HR, 1.32 95% CI, 1.22-1.43) after adjustment for year of diagnosis, American Joint Committee on Cancer stage, age, sex, subsite, race, and marital status. Stage III disease (HR, 0.59 95% CI, 0.54-0.65), glottic subsite (HR, 0.74 95% CI, 0.67-0.82), 2004 to 2009 year-of-diagnosis cohort (HR, 0.79 95% CI, 0.70-0.90), female sex (HR, 0.80 95% CI, 0.72-0.89), and married status (HR, 0.68 95% CI, 0.62-0.75) positively affected DSS. Black race (HR, 1.17 95% CI, 1.05-1.30) and increased age (HR, 1.03 95% CI, 1.02-1.03 for each year) negatively affected DSS.
Surgical therapy leads to better survival outcomes than nonsurgical therapy for patients with advanced laryngeal cancer. Patients need to be made aware of the modest but significant survival disadvantage associated with nonsurgical therapy as part of the shared decision-making process during treatment selection.
Patients with head and neck squamous cell carcinoma (HNSCC) are at elevated risk of second primary malignancies (SPM), most commonly of the head and neck (HN), lung, and esophagus. Our objectives ...were to identify HNSCC subsite-specific differences in SPM risk and distribution and to describe trends in risk over 3 decades, before and during the era of human papillomavirus (HPV) -associated oropharyngeal SCC.
Population-based cohort study of 75,087 patients with HNSCC in the Surveillance, Epidemiology, and End Results (SEER) program. SPM risk was quantified by using standardized incidence ratios (SIRs), excess absolute risk (EAR) per 10,000 person-years at risk (PYR), and number needed to observe. Trends in SPM risk were analyzed by using joinpoint log-linear regression.
In patients with HNSCC, the SIR of second primary solid tumor was 2.2 (95% CI, 2.1 to 2.2), and the EAR was 167.7 cancers per 10,000 PYR. The risk of SPM was highest for hypopharyngeal SCC (SIR, 3.5; EAR, 307.1 per 10,000 PYR) and lowest for laryngeal SCC (SIR, 1.9; EAR, 147.8 per 10,000 PYR). The most common SPM site for patients with oral cavity and oropharynx SCC was HN; for patients with laryngeal and hypopharyngeal cancer, it was the lung. Since 1991, SPM risk has decreased significantly among patients with oropharyngeal SCC (annual percentage change in EAR, -4.6%; P = .03).
In patients with HNSCC, the risk and distribution of SPM differ significantly according to subsite of the index cancer. Before the 1990s, hypopharynx and oropharynx cancers carried the highest excess risk of SPM. Since then, during the HPV era, SPM risk associated with oropharyngeal SCC has declined to the lowest risk level of any subsite.
Head and neck cancers, including those of the lip and oral cavity, nasal cavity, paranasal sinuses, oropharynx, larynx and nasopharynx represent nearly 700,000 new cases and 380,000 deaths worldwide ...per annum, and account for over 10,000 annual deaths in the United States alone. Improvement in outcomes are needed for patients with recurrent and or metastatic squamous cell carcinoma of the head and neck (HNSCC). In 2016, the US Food and Drug Administration (FDA) granted the first immunotherapeutic approvals - the anti-PD-1 immune checkpoint inhibitors nivolumab and pembrolizumab - for the treatment of patients with recurrent squamous cell carcinoma of the head and neck (HNSCC) that is refractory to platinum-based regimens. The European Commission followed in 2017 with approval of nivolumab for treatment of the same patient population, and shortly thereafter with approval of pembrolizumab monotherapy for the treatment of recurrent or metastatic HNSCC in adults whose tumors express PD-L1 with a ≥ 50% tumor proportion score and have progressed on or after platinum-containing chemotherapy. Then in 2019, the FDA granted approval for PD-1 inhibition as first-line treatment for patients with metastatic or unresectable, recurrent HNSCC, approving pembrolizumab in combination with platinum and fluorouracil for all patients with HNSCC and pembrolizumab as a single agent for patients with HNSCC whose tumors express a PD-L1 combined positive score ≥ 1. These approvals marked the first new therapies for these patients since 2006, as well as the first immunotherapeutic approvals in this disease. In light of the introduction of these novel therapies for the treatment of patients with head and neck cancer, The Society for Immunotherapy of Cancer (SITC) formed an expert committee tasked with generating consensus recommendations for emerging immunotherapies, including appropriate patient selection, therapy sequence, response monitoring, adverse event management, and biomarker testing. These consensus guidelines serve as a foundation to assist clinicians' understanding of the role of immunotherapies in this disease setting, and to standardize utilization across the field for patient benefit. Due to country-specific variances in approvals, availability and regulations regarding the discussed agents, this panel focused solely on FDA-approved drugs for the treatment of patients in the U.S.
Patient-derived xenografts represent the gold standard in pre-clinical research models. The chicken embryo chorioallantoic membrane (CAM) is used in functional studies for studying biological ...processes such as blood vessel development and embryogenesis, biocompatible material testing, and more recently three-dimensional patient-derived xenograft (PDX) tumor modeling. We describe here a detailed method used to readily engraft established mouse PDX and primary patient tumor specimens on the CAM with as little as 25 mg of tissue per embryonated egg.
The burden of human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) is disproportionately high among men, yet empirical evidence regarding the difference in prevalence of ...oral HPV infection between men and women is limited. Concordance of oral and genital HPV infection among men is unknown.
To determine the prevalence of oral HPV infection, as well as the concordance of oral and genital HPV infection, among U.S. men and women.
Nationally representative survey.
Civilian noninstitutionalized population.
Adults aged 18 to 69 years from NHANES (National Health and Nutrition Examination Survey), 2011 to 2014.
Oral rinse, penile swab, and vaginal swab specimens were evaluated by polymerase chain reaction followed by type-specific hybridization.
The overall prevalence of oral HPV infection was 11.5% (95% CI, 9.8% to 13.1%) in men and 3.2% (CI, 2.7% to 3.8%) in women (equating to 11 million men and 3.2 million women nationwide). High-risk oral HPV infection was more prevalent among men (7.3% CI, 6.0% to 8.6%) than women (1.4% CI, 1.0% to 1.8%). Oral HPV 16 was 6 times more common in men (1.8% CI, 1.3% to 2.2%) than women (0.3% CI, 0.1% to 0.5%) (1.7 million men vs. 0.27 million women). Among men and women who reported having same-sex partners, the prevalence of high-risk HPV infection was 12.7% (CI, 7.0% to 18.4%) and 3.6% (CI, 1.4% to 5.9%), respectively. Among men who reported having 2 or more same-sex oral sex partners, the prevalence of high-risk HPV infection was 22.2% (CI, 9.6% to 34.8%). Oral HPV prevalence among men with concurrent genital HPV infection was 4-fold greater (19.3%) than among those without it (4.4%). Men had 5.4% (CI, 5.1% to 5.8%) greater predicted probability of high-risk oral HPV infection than women. The predicted probability of high-risk oral HPV infection was greatest among black participants, those who smoked more than 20 cigarettes daily, current marijuana users, and those who reported 16 or more lifetime vaginal or oral sex partners.
Sexual behaviors were self-reported.
Oral HPV infection is common among U.S. men. This study's findings provide several policy implications to guide future OPSCC prevention efforts to combat this disease.
National Cancer Institute.
It is widely accepted that many cancers express features of inflammation, driven by both microenvironmental cells and factors, and the intrinsic production of inflammation-associated mediators from ...malignant cells themselves. Inflammation results in intracellular oxidative stress with the ultimate biochemical oxidants composed of reactive nitrogens and oxygens. Although the role of inflammation in carcinogensis is well accepted, we now present data showing that inflammatory processes are also active in the maintenance phase of many aggressive forms of cancer. The oxidative stress of inflammation is proposed to drive a continuous process of DNA adducts and crosslinks, as well as posttranslational modifications to lipids and proteins that we argue support growth and survival. In this perspective, we introduce data on the emerging science of inflammation-driven posttranslational modifications on proteins responsible for driving growth, angiogenesis, immunosuppression, and inhibition of apoptosis. Examples include data from human melanoma, breast, head and neck, lung, and colon cancers. Fortunately, numerous antioxidant agents are clinically available, and we further propose that the pharmacologic attenuation of these inflammatory processes, particularly the reactive nitrogen species, will restore the cancer cells to an apoptosis-permissive and growth-inhibitory state. Our mouse model data using an arginine antagonist that prevents enzymatic production of nitric oxide directly supports this view. We contend that selected antioxidants be considered as part of the cancer treatment approach, as they are likely to provide a novel and mechanistically justified addition for therapeutic benefit.
Here we show that iNOS-deficient mice display enhanced classically activated M1 macrophage polarization without major effects on alternatively activated M2 macrophages. eNOS and nNOS mutant mice show ...comparable M1 macrophage polarization compared with wild-type control mice. Addition of N6-(1-iminoethyl)-L-lysine dihydrochloride, an iNOS inhibitor, significantly enhances M1 macrophage polarization while S-nitroso-N-acetylpenicillamine, a NO donor, suppresses M1 macrophage polarization. NO derived from iNOS mediates nitration of tyrosine residues in IRF5 protein, leading to the suppression of IRF5-targeted M1 macrophage signature gene activation. Computational analyses corroborate a circuit that fine-tunes the expression of IL-12 by iNOS in macrophages, potentially enabling versatile responses based on changing microenvironments. Finally, studies of an experimental model of endotoxin shock show that iNOS deficiency results in more severe inflammation with an enhanced M1 macrophage activation phenotype. These results suggest that NO derived from iNOS in activated macrophages suppresses M1 macrophage polarization.
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