Background/Objectives: Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer, with a lifetime risk of 14–20% that is rising every year. Although prognosis for cSCC is generally good, certain high-risk features of cSCC portend increased rates of nodal and distant metastasis, recurrence, and disease-specific mortality. One such high-risk factor is perineural invasion (PNI), which is broadly defined as the invasion of cancer into and around nerves. Compared to other high-risk factors, PNI presence is associated with the highest risk for locoregional and distant metastasis. Still, the mechanisms underlying the pathogenesis of PNI remain poorly understood. Recent studies suggest the migration and invasion of tumors into nerves is a result of complex molecular crosstalk within the tumor-nerve microenvironment, wherein the milieu of signaling molecules simultaneously promote neuronal growth and tumor cell invasion. Methods: Understanding the molecular and cellular mechanisms that promote PNI will lead to future developments of targeted therapies that may improve locoregional control and survival. Results/Conclusions: In our article, we aim to provide a comprehensive review of recent findings about the pathogenesis of PNI, clinical implications of PNI-positive disease in cSCC, available treatment modalities, and potential future therapeutic targets.

BACKGROUND With the coronavirus outbreak of 2019 (COVID-19) escalating in early 2020 came many changes in how health care is accessed and delivered. Perhaps most notable is the massive expansion of telemedicine usage, especially in the developed world. With pandemic-induced economic and health care system disruptions, it is reasonable to expect changes in how health care services are utilized by different patients. OBJECTIVE To examine how health care usage trends changed for various patient demographics from the pre-COVID-19 era to the COVID-19 era. METHODS De-identified patient demographics and telemedicine, inpatient, in-person outpatient, radiology/procedures, and emergency department visit data (N = 1,164,719) between January 1st, 2019 and May 31st, 2021 were obtained from the UHealth database. Descriptive statistics and other tools were used to determine relationships between patient demographics and health system usage. RESULTS There were insignificant changes in health care usage and demographics for UHealth services from the pre-COVID-19 era to the COVID-19 era. There was an increase in telehealth visits and a corollary decrease of in-person outpatient visits (P < .001) along with increased health care utilization by those with commercial insurance (P < .001) during COVID-19. Lower income patients had increased use of in-person outpatient services (P < .001). Non-Hispanic, English-speaking patients and those with higher median incomes had higher telemedicine usage. CONCLUSIONS COVID-19 emphasizes differences in health care access, particularly telemedicine access, and vulnerability among certain patient demographics. Telehealth usage expanded dramatically, particularly among non-Hispanic and English-speaking populations. During the COVID-19 era, those with lower median incomes and those with commercial insurance used health care resources at higher rates compared to other patient populations. The trends we see are likely multifactorial and reflect changes in patients’ preferences and disparities in care access.