Adam Barsouk

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 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.

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%.

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.

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.

Multiple myeloma (MM) is a plasma cell disorder that is on the rise throughout the world, especially in the US, Australia, and Western Europe. In the US, MM accounts for almost 2% of cancer diagnoses and over 2% of cancer deaths (more than double the global proportion). Incidence has risen by 126% globally and over 40% in the US since 1990, while global mortality has risen by 94% and US mortality has fallen by 18%. The 5 year survival in the US has more than doubled over the past decades with the introduction of new targeted therapies and transplant techniques. Risk factors for MM include age (average age of diagnosis is 69), race (African Americans are over double as likely to be diagnosed), sex (men are at a 1.5× risk), and family history. Diagnosis includes serum or urine electrophoresis and free light-chain assay but requires bone marrow biopsy. It is distinguished from smoldering myeloma and monoclonal gammopathy of undetermined significance by a high (>3 g/dL) level of M-protein (monoclonal light chains) and the presence of CRAB (Hypercalcemia, Renal failure, Anemia, Bone pain) symptoms, which include hypercalcemia, renal failure, anemia, and bone pain, suggesting an end-organ damage. International staging system staging involves beta 2 microglobulin and albumin levels, while the revised system considers prognostic factors such as lactate dehydrogenase levels and chromosomal abnormalities. Front-line management includes induction regimen, maintenance therapy and hematopoietic cell transplantation for eligible patients and bisphosphonates or bone-stimulating agents for the prevention of skeletal events. Treatment for relapsed disease includes newly approved monoclonal antibodies like the CD38-targeting daratumumab, proteasome inhibitors, immunomodulating agents, and investigational therapies such as B cell maturation antigen Chimeric antigen receptor T cells.

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).

Custodial staff are essential to the smooth functioning of a hospital, and yet their financial hardships often go unnoticed in discussions of health care delivery. I share my personal experiences speaking with custodial staff at the University of Pittsburgh Medical Center as they sought and received a raise in the hospital's minimum wage, and observing the lasting effects of such a reform.

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.

Esophageal cancer (EC) is among the most frequent and deadly cancers around the world. While esophageal adenocarcinoma (EAC) has one of the fastest-growing incidences amongst cancers in the US, it also has one of the lowest survival rates due to the limited effective treatment options. Fortunately, in the past decade, two targeted therapies and an immunotherapy agent have been approved by the FDA for metastatic EAC and esophageal squamous cell carcinoma (ESCC), with several more currently being considered for approval. In terms of immunotherapies, in July 2019, the FDA approved the PD1 inhibitor pembrolizumab for second-line treatment of PDL1-positive, advanced or metastatic ESCC. Two years before, pembrolizumab had been approved for the third-line treatment of PDL1-positive EAC. The PD1 inhibitor nivolumab, which was found in one study to outperform chemotherapy irrespective of PDL1 status, has yet to secure FDA approval. In terms of targeted therapies, although as many as 90% of EC cases show upregulated EGFR, anti-EGFR therapy has not been shown to improve survival. Ramucirumab, an antibody targeting both VEGF and HER2/neu receptors, has been approved for the treatment of refractory EAC, while the anti-HER2 monoclonal antibody (mAb) trastuzumab has been approved as front-line treatment for HER2-positive cases which account for approximately 20% of ECs. Although these targeted therapies and immunotherapies have resulted in significant improvements in survival for specific patient populations that are positive for certain biomarkers, such as PDL1 and HER2/neu, the survival rates remain low for a large proportion of the metastatic EC patient population, necessitating the development of further targeted treatment options.