Epidemiology, Risk Factors, and Prevention of Head and Neck Squamous Cell Carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is a group of malignancies, involving the oral cavity, pharynx, hypopharynx, larynx, nasal cavity, and salivary glands, that together compose the seventh most common cancer diagnosis worldwide. With 890,000 new cases and 450,000 deaths annually per GLOBOCAN estimates, HNSCC accounts for roughly 4.5% of cancer diagnoses and deaths. In the developing world, the incidence of HNSCC is growing with increasing consumption of tobacco (smoked or chewed), alcohol, and areca nut (betel quid). Alcohol and tobacco have a synergistic effect, with the heavy consumption of both increasing HNSCC risk 40-fold. In developed nations, HPV-related HNSCC surpasses tobacco- and alcohol-related disease. HPV-related HNSCC more commonly affects the oropharynx, hypopharynx, and larynx than the oral cavity, and is associated with a significantly longer median survival (130 months vs. 20 months). Discrepancies in etiology as well as disparities in lifestyle choices and access to healthcare may account for the greater incidence and poorer survival of HNSCC among minority and lower-socioeconomic-status communities in developed nations. Pharmacotherapy and counseling together have been shown to be effective in promoting smoking and alcohol cessation. Education on cancer risk and community engagement have reduced areca nut consumption in Asia as well as in diaspora communities. HPV vaccination, starting at age 11-12 for both sexes, has been shown to reduce the prevalence of high-risk HPV serologies and prevent pre-cancerous lesions of the cervix, vagina, and vulva. As of 2020, 58.6% of eligible adolescents in the US have received the full two-vaccine series. Increased adoption of vaccination, education on safe sex practices, and routine visual oral screening for high-risk patients would curb growing HNSCC incidence in developed nations.

Valvular Heart Disease Epidemiology.

Valvular heart disease is a rapidly growing cause of global cardiovascular morbidity and mortality with diverse and evolving geographic distribution. The prevalence of rheumatic heart disease, the most common valvular heart disease (affecting approximately 41 million people), has been rising in developing nations, likely due to the expansion of the young adult population and the decrease in premature mortality that has resulted from improved access to antibiotics, microbiological testing, and echocardiography. Rheumatic heart disease has also been rising among the impoverished and, often, indigenous populations of developed nations, spurring public health initiatives that are aimed at alleviating healthcare disparities. Aortic valve stenotic disease is the most commonly occurring valvular pathology in developed nations (afflicting 9 million people worldwide) and its prevalence has been increasing with population aging and the increased prevalence of atherosclerosis. Aortic regurgitation is associated with diastolic, but not systolic, hypertension and it has likewise seen a rise in the developed world. Mitral regurgitation affects 24 million people worldwide, with great variability between and among nations. Primary mitral regurgitation arises as a consequence of myxomatous degeneration and mitral valve prolapse, which is largely due to genetic predispositions, while secondary mitral regurgitation accounts for 65% of cases and arises secondary to dilation and heart failure. Tricuspid regurgitation has become more prevalent in developed nations due to the increased usage of intracardiac pacemakers. Infective endocarditis prevalence has also grown in developed nations, likely due to population aging and the increased utilization of transcatheter valve replacement and prosthetic valves as interventions against the previously discussed valvular pathologies.

US Cancer Screening Recommendations: Developments and the Impact of COVID-19.

The USPSTF and ACS recommend screening for breast, cervical, colorectal, and lung cancers. Rates of cancer screening, diagnosis, and treatment decreased significantly in the US and other developed nations during the height of the COVID-19 pandemic and lockdown (April 2020) and have since recovered, although not to baseline levels in many cases. For breast cancer, the USPSTF recommends biennial screening with mammography for women aged 50−74, while the ACS recommends annual screening for women aged 45−54, who may transition to biennial after 55. Minority and rural populations have lower rates of screening and lower utilization of DBT, which offers superior sensitivity and specificity. Among 20 US health networks in April 2020, mammography rates were down 89.2% and new breast cancer diagnoses down by 50.5%. For cervical cancer, the USPSTF recommends cervical cytology every three years for women 21−65, or cytology+hrHPV co-testing every five years for women aged 30−65. Cervical cancer screening rates declined by 87% in April 2020 and recovered to a 40% decline by June 2020, with American Indians and Asians most severely affected. For colorectal cancer (CRC), the USPSTF and ACS recommend screening for ages 45−75, recently lowered from a starting age of 50. Most commonly-used modalities include annual FIT testing, FIT+DNA testing every three years, and colonoscopy every ten years, with shorter repeat if polyps are found. In the US, CRC screenings were down by 79−84.5% in April 2020 across several retrospective studies. Patient encounters for CRC were down by 39.9%, and a UK-based model predicted that 5-year-survival would decrease by 6.4%. The USPSTF recommends screening low dose CT scans (LDCTs) for ages 50−80 with a >20 pack-year smoking history who have smoked within the past 15 years. In April 2020, screening LDCTs fell by 72−78% at one US institution and lung cancer diagnoses were down 39.1%.

Epidemiology of Melanoma.

Melanoma accounts for 1.7% of global cancer diagnoses and is the fifth most common cancer in the US. Melanoma incidence is rising in developed, predominantly fair-skinned countries, growing over 320% in the US since 1975. However, US mortality has fallen almost 30% over the past decade with the approval of 10 new targeted or immunotherapy agents since 2011. Mutations in the signaling-protein BRAF, present in half of cases, are targeted with oral BRAF/MEK inhibitor combinations, while checkpoint inhibitors are used to restore immunosurveillance likely inactivated by UV radiation. Although the overall 5-year survival has risen to 93.3% in the US, survival for stage IV disease remains only 29.8%. Melanoma is most common in white, older men, with an average age of diagnosis of 65. Outdoor UV exposure without protection is the main risk factor, although indoor tanning beds, immunosuppression, family history and rare congenital diseases, moles, and obesity contribute to the disease. Primary prevention initiatives in Australia implemented since 1988, such as education on sun-protection, have increased sun-screen usage and curbed melanoma incidence, which peaked in Australia in 2005. In the US, melanoma incidence is not projected to peak until 2022-2026. Fewer than 40% of Americans report practicing adequate protection (sun avoidance from 10 a.m.-4 p.m. and regular application of broad-spectrum sunscreen with an SPF > 30). A 2-4-fold return on investment is predicted for a US sun-protection education initiative. Lesion-directed skin screening programs, especially for those at risk, have also cost-efficiently reduced melanoma mortality.

Epidemiology of lung cancer.

Lung cancer is the leading cause of global cancer incidence and mortality, accounting for an estimated 2 million diagnoses and 1.8 million deaths. Neoplasms of the lungs are the second most common cancer diagnosis in men and women (after prostate and breast cancer, respectively). With increasing access to tobacco and industrialization in developing nations, lung cancer incidence is rising globally. The average age of diagnosis is 70 years old. Men are twice as likely to be diagnosed with lung cancer, which largely reflects differences in tobacco consumption, although women may be more susceptible due to higher proportions of epidermal growth factor receptor mutations and the effects of oestrogen. African American men in the US are at the highest risk of lung cancer. Family history increases risk by 1.7-fold, with a greater risk among first-degree relatives. Tobacco smoking is the greatest preventable cause of death worldwide, accounting for up to 90% of lung cancer cases, and continued consumption is projected to increase global cancer incidence, particularly in developing nations such as China, Russia, and India. Second-hand smoke among children and spouses has likewise been implicated. Radon from natural underground uranium decay is the second leading cause of lung cancer in the developed world. Occupational hazards such as asbestos and environmental exposures such as air pollution, arsenic, and HIV and Tb infection have all been implicated in lung carcinogenesis, while cannabis smoking, electronic cigarettes, heated tobacco products, and COVID-19 have been hypothesized to increase risk.

Epidemiology of Non-Hodgkin's Lymphoma.

Non-Hodgins's lymphoma (NHL) is the most common hematological malignancy worldwide, accounting for nearly 3% of cancer diagnoses and deaths. NHL is the seventh most prevalent cancer and has the sixth highest mortality among cancers in the US. NHL accounts for 4% of US cancer diagnoses, and incidence has increased 168% since 1975 (while survival has improved 158%). NHL is more common among men, those >65 years old, and those with autoimmune disease or a family history of hematological malignancies. NHL is a heterogenous disease, with each subtype associated with different risk factors. Marginal zone lymphoma (MZL) is strongly associated with Sjogren's syndrome (SS) and Hashimoto's thyroiditis, while peripheral T-cell lymphoma (PTCL) is most associated with celiac disease. Occupational exposures among farm workers or painters increases the risk of most of the common subtypes. Prior radiation treatment, obesity, and smoking are most highly associated with diffuse large B-cell lymphoma (DLBCL), while breast implants have been rarely associated with anaplastic large cell lymphoma (ALCL). Infection with Epstein-Barr Virus (EBV) is strongly associated with endemic Burkitts lymphoma. HIV and human herpes virus 8 (HHV-8), is predisposed to several subtypes of DLBCL, and human T-cell lymphoma virus (HTLV-1) is a causative agent of T-cell lymphomas. Obesity and vitamin D deficiency worsen NHL survival. Atopic diseases and alcohol consumption seem to be protective against NHL.

Epidemiology, Staging and Management of Prostate Cancer.

Prostate cancer is the second most common and fifth most aggressive neoplasm among men worldwide. It is particularly incident in high human development index (HDI) nations, with an estimated one in seven men in the US receiving a prostate cancer diagnosis in their lifetime. A rapid rise and then fall in prostate cancer incidence in the US and Europe corresponded to the implementation of widespread prostate specific antigen (PSA) testing in 1986 and then subsequent fall from favor due to high rates of false positives, overdiagnosis, and overtreatment (as many as 20-50% of men diagnosed could have remained asymptomatic in their lifetimes). Though few risk factors have been characterized, the best known include race (men of African descent are at higher risk), genetics (e.g., BRCA1/2 mutations), and obesity. The Gleason scoring system is used for histopathological staging and is combined with clinical staging for prognosis and treatment. National guidelines have grown more conservative over the past decades in management, recommending watchful waiting and observation in older men with low to intermediate risk disease. Among higher risk patients, prostatectomy (robotic is preferred) and/or external beam radiotherapy is the most common interventions, followed by ADT maintenance. Following progression on androgen deprivation therapy (ADT) (known as castration-resistance), next generation endocrine therapies like enzalutamide, often in combination with cytotoxic agent docetaxel, are standard of care. Other promising treatments include Radium-223 for bone metastases, pembrolizumab for programmed death ligand-1 (PDL1) and microsatellite instability (MSI) high disease, and poly ADP ribose polymerase (PARP) inhibitors for those with mutations in homologous recombination (most commonly BRCA2).

Epidemiology of Renal Cell Carcinoma.

Though renal cell carcinoma (RCC) accounts for 2% of global cancer diagnoses and deaths, it has more than doubled in incidence in the developed world over the past half-century, and today is the ninth most common neoplasm in the United States (US). While North America and Western Europe have the highest disease burden (with the Belarus highest in incidence), Latin America, Asia and Africa are projected to see an increase in incidence as nation's transition to a Western lifestyle. Most cases of RCC are discovered incidentally on imaging, and survival is highly dependent on the stage at diagnosis, with the metastatic disease having only a 12% 5-year survival rate. Two-thirds of RCC diagnoses are made in men, and the average age of diagnosis in the US is 64. Those with genetic predispositions, namely von Hippel-Lindau disease, tend to be diagnosed 20 years earlier. RCC has a greater incidence among Hispanics and Native Americans, and a lower survival rate among African Americans in the US. Modifiable risk factors for RCC include smoking, obesity, poorly-controlled hypertension, diet and alcohol, and occupational exposures. Prevention strategies aimed at improving survival and reducing disparities include addressing lifestyle factors and access to regular healthcare among underserved populations and in developing nations, as well as more rigorous imaging guidelines to detect RCC at an earlier stage. A stronger understanding of global RCC epidemiology can facilitate prevention efforts, especially in developing nations and underserved communities where disease burden is predicted to rise in the coming decades.

Epidemiology of Bladder Cancer.

Based on the latest GLOBOCAN data, bladder cancer accounts for 3% of global cancer diagnoses and is especially prevalent in the developed world. In the United States, bladder cancer is the sixth most incident neoplasm. A total of 90% of bladder cancer diagnoses are made in those 55 years of age and older, and the disease is four times more common in men than women. While the average 5-year survival in the US is 77%, the 5-year survival for those with metastatic disease is a measly 5%. The strongest risk factor for bladder cancer is tobacco smoking, which accounts for 50-65% of all cases. Occupational or environmental toxins likewise greatly contribute to disease burden (accounting for an estimated 20% of all cases), though the precise proportion can be obscured by the fact bladder cancer develops decades after exposure, even if the exposure only lasted several years. Schistosomiasis infection is the common cause of bladder cancer in regions of Africa and the Middle East and is considered the second most onerous tropical pathogen after malaria. With 81% of cases attributable to known risk factors (and only 7% to heritable mutations), bladder cancer is a prime candidate for prevention strategies. Smoking cessation, workplace safety practices, weight loss, exercise and schistosomiasis prevention (via water disinfection and mass drug administration) have all been shown to significantly decrease the risk of bladder cancer, which poses a growing burden around the world.

Chemical Risk Factors of Primary Liver Cancer: An Update.

Primary liver cancer has the sixth highest incidence and fourth highest cancer mortality worldwide. Hepatitis B is the leading cause of liver cancer, though its incidence is decreasing with vaccination. Alcohol is the leading cause of liver transplant, cirrhosis, and cancer in the developed world, and is projected to surpass hepatitis B as the leading hepatic cancer etiology worldwide. Tobacco smoking has shown a positive association with liver cancer in a majority of studies, though not all. Aflatoxin, a mycotoxin produced by Aspergillus, is estimated to account for 3-20% of global liver cancer cases, 40% of which occur in sub-Saharan Africa. These statistics are confounded by the prevalence of hepatitis B, which may have a synergistic effect on hepatic carcinogenesis. Aflatoxin is ingested and likely inhaled from agricultural products, placing farmers, food processors, and textile workers in developing nations at risk. Vinyl-chloride is used in the production of PVC plastics and causes rare liver angiosarcoma, hepatocellular carcinoma, and other neoplasms. Arsenic and cadmium are naturally-occurring, hepatocarcinogenic metals with high occupational exposure in industries involving coal, metals, plastics, and batteries. Millions of laborers in waste-disposal and manufacturing are exposed to organic solvents and N-nitrosamines, which vary from carcinogenic (group 1) to possibly carcinogenic (group 2B) in their IARC designation. Insecticide DDT is possibly hepatocarcinogenic (group 2B), though continues to be used for malaria control in the developing world. While suggested by case reports, anabolic steroids and oral contraceptives have not been shown to increase liver cancer risk in large studies.

Epidemiology of non-alcoholic fatty liver disease and risk of hepatocellular carcinoma progression.

Non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease worldwide. Its incidence has grown alongside the increasing global prevalence of type 2 diabetes, obesity, and metabolic syndrome. The risk of progression to hepatocellular carcinoma for nonalcoholic steatohepatitis patients over 5 years is 8%, and despite targeted and immunotherapy treatment advances, HCC maintains a bleak 5-year survival of 19%. NAFLD's primary risk factors are components of metabolic syndrome as well as possible sleep disturbances. NAFLD is most common among men 50-60 years of age, though incidence in women catches up after menopause. In the US, Hispanics are most likely to develop NAFLD and African Americans least likely, in part due to the prevalence of the PNPLA3 gene variant. With NAFLD risk factors especially prevalent in underserved populations and developing nations, public health interventions, earlier diagnosis, and novel treatments could curb the growing disease burden.

Impact of acetylsalicylic acid on primary prevention of cardiovascular diseases: A meta-analysis of randomized trials.

Numerous studies have investigated use of acetylsalicylic acid (ASA) for prevention of cardiovascular deaths. The vast majority of the work in this area has focused on secondary prevention. However, underuse of ASA still remains a major issue. Fewer studies have investigated the impact of ASA on primary prevention of cardiovascular death. A meta-analysis of individual participant data from six randomized studies, published in 2009, showed decrease in serious vascular events but at the cost of causing increased bleeding and hemorrhagic stroke. Recent studies have raised a number of key questions regarding the benefits and risks of using ASA for primary prevention.

Impact of cyclosporine A use in the prevention of reperfusion injury in acute myocardial infarction: A meta-analysis.

BACKGROUND: Reperfusion injury is an important limiting factor associated with revascularization in acute myocardial infarction (AMI). Various therapies have been tried in an attempt to prevent reperfusion injury, but the search has been elusive. The role of cyclosporine A (CsA) in the prevention of reperfusion injury in AMI is still not clear. The objective of this study was to find out whether CsA is beneficial in reducing reperfusion injury in acute ST elevation myocardial infarction. METHODS: We performed a systematic search of Pubmed, Scopus, clinicaltrial.gov, and Cochrane Database for randomized control trials (RCT) measuring the effect of CsA in AMI compared to a placebo. The Mantel-Haenszel method and random effect model were used to analyze the data. A total of 1,566 patients (776 in the CsA group and 790 in the placebo group), who participated in 5 RCTs were included in our meta-analysis. RESULTS: We did not find any significant differences between the CsA and placebo groups in terms of all-cause death (odds ratio [OR] 1.21, 95% confidence interval [CI] 0.78-1.87) and cardiovascular death (OR 1.05, 95% CI 0.66-2.49). Similarly, we did not find any significant differences in terms of cardiogenic shock, recurrent ischemia and myocardial infarction, heart failure and echocardiographic outcomes. CONCLUSIONS: Cyclosporine A is not helpful in preventing reperfusion injury in AMI.