Incidence Of Squamous Cell Carcinoma Research Articles

Rising Trend in the Prevalence of HPV-Driven Oropharyngeal Squamous Cell Carcinoma during 2000-2022 in Northeastern Italy: Implication for Using p16INK4a as a Surrogate Marker for HPV-Driven Carcinogenesis.

The prevalence and incidence of oropharyngeal squamous cell carcinomas (OPSCCs) driven by human papillomavirus (HPV) infection are increasing worldwide, being higher in high-income countries. However, data from Italy are scanty. p16INK4a overexpression is the standard in determining HPV-driven carcinogenesis, but disease prevalence impacts on its positive predictive value. This is a multicenter retrospective study enrolling 390 consecutive patients aged ≥18 years, diagnosed with pathologically confirmed OPSCC in Northeastern Italy between 2000 and 2022. High-risk HPV-DNA and p16INK4a status were retrieved from medical records or evaluated in formalin-fixed paraffin-embedded specimens. A tumor was defined as HPV-driven when double positive for high-risk HPV-DNA and p16INK4a overexpression. Overall, 125 cases (32%) were HPV-driven, with a significant upward temporal trend from 12% in 2000-2006 to 50% in 2019-2022. The prevalence of HPV-driven cancer of the tonsil and base of the tongue increased up to 59%, whereas it remained below 10% in other subsites. Consequently, the p16INK4a positive predictive value was 89% for the former and 29% for the latter. The prevalence of HPV-driven OPSCC continued to increase, even in the most recent period. When using p16INK4a overexpression as a surrogate marker of transforming HPV infection, each institution should consider the subsite-specific prevalence rates of HPV-driven OPSCC as these significantly impact on its positive predictive value.

Analysis of risk factors and management of unexpected intraoperative bleeding during video-assisted thoracic surgery for non-small cell lung cancer: a case-control study.

Intraoperative bleeding is one of the most dangerous complications of thoracoscopic surgery and seriously endangers the life of patients. How to prevent and manage intraoperative bleeding is a core concern for every thoracic surgeon. The aim of our study was to analyze the related risk factors of unexpected intraoperative bleeding during video-assisted thoracoscopic surgery (VATS) and the strategies for managing bleeding. A total of 1,064 patients who underwent anatomical pulmonary resection were analyzed retrospectively. According to the presence or absence of intraoperative bleeding, all cases were divided into an intraoperative bleeding group (IBG) and a reference group (RG). Clinicopathological characteristics and perioperative outcomes were compared in both groups. In addition, the sites, reasons, and coping strategies of intraoperative bleeding were summarized and analyzed. After rigorous screening, 67 patients with intraoperative bleeding and 997 patients without intraoperative bleeding were included in our study. Compared with the RG, among patients in the IBG, there was a higher incidence of history of chest surgery (P<0.001), higher incidence of pleural adhesion (P=0.015), higher incidence of squamous cell carcinoma (P=0.034), and the fewer early T-stage cases (P=0.003). In the multivariate analyses, a history of chest surgery (P=0.001) and T stage (P=0.010) were independent risk factors of intraoperative bleeding. The IBG was associated with the longer operative time, the more blood loss, the higher rates of intraoperative blood transfusion and conversion, the longer hospital stay and the more complications. There were no significant differences in the duration of chest drainage (P=0.066) between IBG and RG. The most common injury site of intraoperative bleeding was the pulmonary artery (72%). The commonest cause of intraoperative bleeding was the accidental injury of energy device (37%). The most frequently used method for managing intraoperative bleeding was suturing of the bleeding site (64%). Although unexpected intraoperative bleeding during VATS is unavoidable, it can be controlled provided that positive and effective hemostasis are achieved. However, prevention is the priority.

Immunotherapy in Anal Cancer

The incidence and mortality of squamous cell carcinoma of the anus has been gradually increasing globally over the last few decades. The evolution of different modalities, including immunotherapies, has changed the treatment paradigm of metastatic anal cancers. Chemotherapy, radiation therapy, and immune-modulating therapies form the backbone of treatment of anal cancer in various stages. Most anal cancers are linked to high-risk human papilloma virus (HPV) infections. HPV oncoproteins E6 and E7 are responsible for an anti-tumor immune response triggering the recruitment of tumor-infiltrating lymphocytes. This has led to the development and utilization of immunotherapy in anal cancers. Current research in anal cancer is moving forward to discover ways to incorporate immunotherapy in the treatment sequencing in various stages of anal cancers. Immune checkpoint inhibitors alone or in combination, adoptive cell therapy, and vaccines are the areas of active investigations in anal cancer in both locally advanced and metastatic settings. Immunomodulating properties of non-immunotherapies are incorporated to enhance immune checkpoint inhibitors' effectiveness in some of the clinical trials. The aim of this review is to summarize the potential role of immunotherapy in anal squamous cell cancers and future directions.

Epidemiology of skin cancer based on Japan's National Cancer Registry 2016-2017.

Skin cancer is most frequently diagnosed in the White population. However, its subtypes and epidemiology in Japan are understudied. We aimed to elucidate skin cancer incidence in Japan based on the National Cancer Registry, a new nationwide integrated population-based registry. Data from patients diagnosed with skin cancer in 2016 and 2017 were extracted and classified by cancer subtypes. Data were analyzed using the World Health Organization and General Rules tumor classifications. Tumor incidence was calculated as the number of new cases divided by the corresponding total person-years. Overall, 67,867 patients with skin cancer were included. The percentage of each subtype was as follows: basal cell carcinoma, 37.2%; squamous cell carcinoma, 43.9% (18.3% of which, in situ); malignant melanoma, 7.2% (22.1% of which, in situ); extramammary Paget's disease, 3.1% (24.9% of which, in situ); adnexal carcinoma, 2.9%; dermatofibrosarcoma protuberans, 0.9%; Merkel cell carcinoma, 0.6%; angiosarcoma, 0.5%; and hematologic malignancies, 3.8%. The overall age-adjusted incidence of skin cancer was 27.89 for the Japanese population model and 9.28 for the World Health Organization (WHO) model. The incidences of basal cell carcinoma and squamous cell carcinoma were the highest (3.63 and 3.40 per 100,000 persons, respectively, in the WHO model) among skin cancers, whereas the incidences of angiosarcoma and Merkel cell carcinoma were the lowest (0.026 and 0.038 per 100,000 persons, respectively, in the WHO model). This is the first report to provide comprehensive information on the epidemiological status of skin cancers in Japan using population-based NCR data.

Evaluation of proliferative activity of pre-tumor and tumor processes of Barrett's esophagus using AGNOR technology

Esophageal carcinoma is the eighth most common malignancy and the sixth leading cause of cancer-related death worldwide. Adenocarcinomas account for the majority of esophageal carcinomas in the US. The incidence of esophageal squamous cell carcinomas is decreasing every year, while the number of adenocarcinomas has not changed over the last three to four decades. It has been established that there is a strong correlation between proliferative activity and a poor tumor prognosis, so the interest in clinical trials of proliferative potential on various markers is still relevant and increasing every year. Within the framework of our research, a cohort retrograde study was carried out, for which the archival material of the teaching-scientific and diagnostic laboratory of Tbilisi State Medical University for the years 2019-2022 was used. Proliferative activity was determined by AgNOR technology in 35 cases evaluated in the following histological entity: Barrett's esophagus with enteric metaplasia; Barrett's esophagus with foveolar metaplasia; Barrett's esophagus with low-grade dysplasia of the epithelium; Barrett's esophagus with high-grade dysplasia of the epithelium; Based on the results of our study, AgNOR technology can be used to evaluate proliferative activity in Barrett's esophagus.

Survival of oral tongue cancer in low middle-income country: a cohort study

IntroductionThe incidence of oral tongue squamous cell carcinoma (OTSCC) is increasing. OTSCC is comparatively higher in our region owing to the consumption of tobacco, beetle nut, alcohol, and poor oral hygiene. There is paucity of survival data for OTSCC from our high-burden region.BackgroundThere is paucity of survival data for OTSCC from our high-burden region, we aimed to determine 5-year overall and disease-free survival of patients with OTSCC.MethodsA retrospective chart review was conducted for all the patients treated for oral tongue squamous cell carcinoma from January 2000 and December 2013. The data on overall survival and disease-free survival was collected via telephonic interviews up till 2018. Kaplan Meier curves were plotted to graphically represent survival.ResultsA total of 131 patients were included. The mean age of the patients was 49.4 ± 12.98 years, with most patients being male (65.9%). The most common tumor stage was T2 (55.1%) and the most common nodal stage was N0 (57.7%). Five-year disease-free survival was 59.2%, and overall survival was 60.7%. Overall survival dropped steeply from 84.4 to 7.5% in patients who developed recurrence in our cohort.ConclusionThe most significant factor influencing the survival of patients with OTSCC is tumor recurrence. 5-year recurrence-free survival was 84.4% which is greater than reported in literature. This could be due to the low incidence of perineural and perivascular invasion in our population. Further research on factors leading to recurrence should be done.

Risk of Squamous Cell Carcinoma of the Breast Following Postmastectomy Implant Reconstruction in Women With Breast Cancer and Carcinoma in Situ

This cohort study uses national surveillance data to describe the incidence and risk of squamous cell carcinoma after postmastectomy implant reconstruction in women with breast cancer.

Trends in cutaneous squamous cell carcinoma on the lip incidence and mortality in the United States, 2000-2019.

This study provided a systematic analysis of the trend in incidence and incidence-based mortality for cutaneous squamous cell carcinoma (cSCC) on the lips in the USA using demographic characteristics from the Surveillance, Epidemiology, and End Results (SEER) database. Patients diagnosed with cSCC on the lips between 2000 and 2019 from the 17 registries of the USA were identified. Incidence and incidence-based mortality rates were analyzed using SEER*Stat 8.4.0.1 software. This paper calculated incidence rates and incidence-based mortality rates by 100,000 person-years for sex, age, race, SEER registries, median household income ($/year), rural-urban distribution, and primary site. The annual percent changes (APC) in incidence and incidence-based mortality rates were then calculated using joinpoint regression software. Among 8,625 patients diagnosed with cSCC on the lips from 2000 to 2019, men (74.67%), white (95.21%), and 60-79 years old were the most common population, and 3,869 deaths from cSCC on the lips occurred. The overall incidence of cSCC on the lips was 0.516 per 100,000 person-years. cSCC on the lip incidence rates were highest among men, white, and patients aged 60-79 years old. cSCC on the lip incidence rates decreased by 3.210%/year over the study period. The incidence of cSCC on the lips has been decreasing in all sexes, ages, high- or low-income households, and urban or rural patients. The overall incidence-based mortality rate of cSCC on the lips during 2000-2019 was 0.235 per 100,000 person-years. cSCC on the lip incidence-based mortality rates were highest among men, whites, and people older than 80 years old. cSCC on the lip incidence-based mortality increased by 4.975%/year over the study period. cSCC on the lip incidence-based mortality rates increased for all sexes, races, ages, primary sites, high- or low-income households, and urban or rural patients during the study period. Among patients in the USA diagnosed with cSCC on the lips from 2000 to 2019, the overall incidence decreased by 3.210% annually, and incidence-based mortality increased by 4.975%/year. These findings update and supplement the epidemiological information of cSCC on the lips in the USA.

Human papillomavirus and Epstein-Barr virus co-infection in oral and oropharyngeal squamous cell carcinomas: A systematic review and meta-analysis.

Squamous cell carcinoma of the oral cavity (OSCC) is the most common head-and-neck malignancy. Importantly, we are experiencing an alarming rise in the incidence of oropharyngeal squamous cell carcinoma (OPSCC) globally. Oncogenic viruses, human papillomavirus (HPV) and Epstein-Barr virus (EBV), are known to be co-associated with OSCC and OPSCC cases. However, the reported incidence of HPV and EBV co-infection in OSCCs and OPSCCs globally is unknown. To address this, we performed a formal meta-analysis and systematic review on published studies that report the detection of both EBV and HPV in OSCCs and OPSCCs. Our analysis revealed 18 relevant studies out of a total of 1820 cases (1181 from the oral cavity and 639 from the oropharynx). Overall, HPV and EBV co-infection was found in 11.9% of OSCC and OPSCC cases combined (95% CI: 8%-14.1%). Based on anatomical subsite, dual positivity estimates were 10.5% (95% CI: 6.7%-15.1%) for OSCC and 14.2% (95% CI: 9.1%-21.3%) for OPSCC. The highest dual positivity rates described were in European countries: for OSCC 34.7% (95% CI: 25.9%-44.6%) in Sweden and for OPSCC, 23.4% (95% CI: 16.9%-31.5%) in Poland. Given these substantive prevalence rates, the value of detecting dual infection in the diagnosis and prognosis of these cancers deserves careful longitudinal studies, as do implications for cancer prevention and therapy. We further proposed molecular mechanisms that could explain how HPV and EBV could co-contribute to the aetiology of OSCCs and OPSCCs.

Expression of Human Papillomavirus and the p16 Gene in Oral Potentially Malignant Disorders (OPMD): a Comparative Study With Oral Squamous Cell Carcinoma.

The incidence of oral squamous cell carcinoma (OSCC) of the tongue is increasing in the younger population without traditional risk habits that lead researchers to find other related factors such as diet and viruses, especially human papillomavirus (HPV). It is noteworthy that many OSCCs develop from oral potentially malignant disorders (OPMDs). Correct diagnosis and timely management of OPMDs may help to prevent malignant transformation, and therefore it is worth seeing the involvement of HPV in OPMDs and oral cancers, as the preventive and curative measures in HPV-induced cancer types are different from the conventional types of OPMDs and OSCCs. Therefore, the main objective of this study was to identify a relationship between HPV and p16 in OPMDs and compare it with OSCC. This study was conducted on 83 cases of known OSCCs and OPMDs (oral submucous fibrosis, leukoplakia, and oral lichen planus). Assays, such as polymerized chain reaction (PCR) and reverse transcription-PCR, were carried out for HPV and p16. The results were compared with clinical information and with the literature. The results were analyzed using SPSS 16.0 for windows. P16 expression was mostly seen in males than in female patients. Out of 21 cases of keratosis with dysplasia, 19% expressed p16. Of 26 oral lichen planus patients, 29% showed the p16 gene with immunohistochemistry. Interestingly, a high percentage of OSF cases expressed p16 (48.27%). Minimal expression was observed in OSCC (6.25%). HPV DNA was detected in 2.4% of the total sample. Both p16 and HPV were detected in a single case of OSCC. OPMDs expressed a significant amount of the p16 gene by immunohistochemistry and reverse transcription-PCR technique when compared with malignant lesions, suggesting a possible inactivation of the p16 gene. HPV and p16 are mostly negative in our OSCC sample, exhibiting low prevalence. OPMDs expressed a significant amount of the p16 gene when compared with malignant lesions, suggesting a possible inactivation of the p16 gene. Although OSF expressed p16, HPV was not detected, suggesting that over-expression could be independent of HPV. OSCC shows low HPV prevalence.

Abstract 2217: Novel risk stratification utilizing NanoString for HPV+ head and neck cancer patients

Abstract Incidence of human papillomavirus positive (HPV+) head and neck squamous cell carcinoma (HNSCC) has dramatically increased in the U.S. surpassing cervical cancer since 2012. Among HNSCC, HPV+ HNSCC patients have a favorable prognosis; however, approximately 20-30% suffer recurrence. Given the morbidity of current therapy, therapeutic de-escalation for HPV+ HNSCC is being explored in many clinical trials but is hampered by absence of accurate molecular classifiers to identify tumors at high and low risk of recurrence. Being able to risk stratify patients can help with therapeutic decisions, maintain high cure rates and decrease treatment associated complications. We assemble a NanoString panel to capture our recently developed NF-κB RNA signature that can distinguish patients requiring aggressive therapy from patients who are appropriate for reduced intensity treatment. Our custom gene set can select HPV+ head and neck cancer patients that may benefit from therapy de-escalation. Several advantages of using a NanoString technology, including smaller amounts of patient samples and less processing time that allow real-time patient-specific results. This makes our Nanostring panel suitable to be used in clinic to identify HPV+ head and neck cancer patients for therapeutic de-escalation without compromising their survival. Citation Format: Sulgi Kim, Travis Schrank, Aditi Kothari, Hina Rehmani, Jason Tasoulas, Xue Li, Wendell Yarbrough, Natalia Isaeva. Novel risk stratification utilizing NanoString for HPV+ head and neck cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2217.

Abstract 3925: JunB regulates expression of HPV genes in head and neck cancer

Abstract The incidence of HPV-positive head and neck squamous cell carcinoma (HNSCC) is now being considered an epidemic in the US and Western Europe as rates have surpassed those for cervical cancer. For approximately 14,400 patients per year in the US, initial therapy is aggressive and often results in adverse lifelong side effects such as difficulty swallowing and speaking. Despite having a higher cure rate than HPV-negative HNSCC, the recurrence rate is still approximately 30%. Therefore, new treatment options need to be available for these relapsed patients. Our lab was prompted to explore demethylation as a therapeutic option as HPV-positive HNSCC have a more hypermethylated genome than HPV-negative cancers. 5-azacytidine (5-aza) is a synthetic cytidine analog that causes DNA demethylation by trapping methyltransferases to chromatin; it is FDA-approved for the treatment of myelodysplasia and acute myeloid leukemia. Our lab found that low doses of 5-aza delayed HPV-positive xenograft tumor growth and that HPV-positive tumor samples from patients treated with 5-aza in a window trial had increased apoptosis. They also observed a marked downregulation of HPV gene expression after 5-aza. Decreased HPV E6 expression, followed by reactivation of tumor suppressor p53, induced p53-dependent apoptosis in HPV-positive HNSCC. To further explore the mechanism of this sensitivity to 5-Aza, we first determined that 5-aza regulates the transcription of HPV genes, but not the stability of HPV transcripts. We found that the transcriptional regulation of HPV genes after 5-aza depends on the proto-oncogene JunB, a component of the transcription factor Activator Protein 1 (AP-1). Additionally, silencing of JunB abolished the expression of HPV E6/E7 genes and reactivated tumor suppressor p53 in HPV-positive HNSCC. Furthermore, we revealed that clonogenic survival of HPV-positive head and neck cancer cells is dependent on JunB expression. Our study exposes an important component of 5-Aza-associated sensitivity and toxicity in HPV-positive HNSCC and identifies a novel dependency on JunB, potentially providing a new rational targeted therapy. Citation Format: Hina Rehmani, Travis P. Schrank, Natalia Issaeva, Wendell G. Yarbrough. JunB regulates expression of HPV genes in head and neck cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3925.

Keratinocyte Carcinoma Chemoprevention With a Combination of Imiquimod, 5-Fluorouracil, and Tretinoin.

The incidence of keratinocyte carcinomas (KCs), comprising basal and squamous cell carcinomas, is rising in the United States. Chemoprevention is one modality by which patients can reduce the incidence of KCs. We performed a retrospective review of 327 patients who employed a combination of imiquimod 5% cream, 5-fluorouracil 2% solution, and tretinoin 0.1% cream in a field therapy regimen over the face/ears or scalp for chemoprevention. Patients had dramatically lower odds of having KCs in the treatment location (face/ears or scalp) in the one-year period after field treatment than in the one-year period preceding field treatment (OR=0.06, 95% CI: [0.02, 0.15]). Patients were also at lower odds of having KCs in non-treated areas the year after field treatment than in the year preceding it (OR=0.25, 95% CI: [0.14, 0.42]). Additionally, fewer cryotherapy sessions were performed for actinic keratoses in the treatment areas in the year after treatment (mean=1.5, SD=1.21) than the year preceding treatment (mean=2.3, SD=0.99; t=11.68, P&lt;0.001). A combination of imiquimod 5% cream, 5-fluorouracil 2% solution, and tretinoin 0.1% cream were effective at reducing the incidence of new KCs for at least one year. Individualized treatment application frequency allowed for increased patient adherence. Prospective studies evaluating combination topical treatments for chemoprevention of KCs are needed to further assess the treatment effects found in this study. J Drugs Dermatol. 2023;22(5): doi:10.36849/JDD.7334.

Epidemiology and incidence of oral squamous cell carcinoma in the Iraqi population over 5 years (2014-2018).

Oral squamous cell carcinoma is one of the most common and life-threatening neoplasms worldwide, and is responsible for approximately 90% of all oral malignancies. This study was aimed at providing updated information on oral squamous cell carcinoma in all Iraqi governorates for the 5-year period from 2014 to 2018, including the annual incidence and demographic variables. The total number of oral squamous cell carcinoma cases in Iraq, along with associated demographic information (age, sex, and site), for the 5-year period from 2014 to 2018 was obtained. The statistical analysis consisted of descriptive analysis, including frequency, percentage, and mean ± standard deviation. A χ 2 test was performed to compare frequencies between male and female patients, among age groups, and among different OSCC sites. The χ 2 test was also used to assess the association of each OSCC site with age and sex. The significance threshold was set at p < 0.05, and the confidence interval was set at 95%. The incidence rate of oral squamous cell carcinoma for each year was calculated by dividing the number of OSCC cases per year by the population of Iraq, then multiplying the result by 100,000. A total of 722 cases were recorded. Statistically, oral squamous cell carcinoma was found to be more prevalent in males and individuals over 40 years of age. The tongue was the most common site of occurrence. Lip squamous cell carcinoma cases were high in males. The incidence rate of oral squamous cell carcinoma was estimated to be 0.4 per 100,000 people. Males and older people are at relatively higher risk of developing oral cancer. The tongue is the most affected site, but any site in the oral cavity may be involved. Further exploration of the causes of oral malignancy in Iraq is necessary to improve prevention strategies.

Human Papillomavirus Vaccination and Cervical Cancer Risk

ABSTRACT The progression of high-risk human papillomavirus (hrHPV) to cervical cancer is well characterized, and risk factors for hrHPV including genetic predisposition, hormonal factors, host immune response, and cigarette smoking are well documented. Prevention of cervical cancer primarily relies on preventing hrHPV infection through vaccination, as well as treatment of precancerous lesions (high-grade cervical intraepithelial neoplasia [CIN2/3] or adenocarcinoma in situ [ACIS]). Bivalent, quadrivalent, and nonavalent HPV vaccines are prequalified by the World Health Organization (WHO) and widely licensed; however, less than 25% of low-income countries have HPV vaccination as part of their national immunization schedules. The WHO set a target for 194 countries to adopt HPV vaccination by 2030, and this article summarizes clinical data on the efficacy and effectiveness of HPV vaccination, its potential impact on incidence of invasive cervical squamous cell carcinoma (ICC), and strategies to increase access to and uptake of vaccination. Large online databases were searched for randomized control trials and population-based cohort studies in which HPV vaccination and pathologic diagnosis were documented in the data set. Several large-scale studies including a Cochrane review of 73,428 participants and a meta-analysis of more than 60 million, and data from National registries in Sweden, Japan, and the United Kingdom demonstrated that HPV vaccination is safe and leads to prevention of cervical precancer. In April 2022, the WHO updated its recommendation to be 1 or 2 doses for girls aged 9–14 years; 1 or 2 doses for girls aged 15–20 years; and 2 doses separated by 6 months for women older than 21. Eight of every 10 cases of IIC occur in low- and middle-income countries (LMICs), and ICC is the leading cause of death from cancer among women in sub-Saharan Africa. Disparities among these countries are driven by inequity in access to prevention and treatment of cancer. Global HPV vaccination coverage for girls is approximately 18% for a first dose and 13% for series completion. On the supply side, barriers to vaccination include prohibitive cost of vaccines for many LMICs and the requirement for refrigeration of all licensed vaccines. Promisingly, a new quadrivalent prophylactic HPV vaccine is becoming available in 2023 in India that may significantly reduce the cost of vaccine doses and may not require refrigeration. On the demand side, misinformation, cultural views on sex, and mistrust of the medical system are major barriers. According to data from 37 registries in 20 countries, without changing the rate of HPV vaccination or cervical cancer screening, the global burden will increase from an estimated 600,000 in 2020 to 1.3 million in 2069. Models demonstrate that a rapid scale up of HPV vaccination to more than 80% of adolescent girls and continued or increased screening could result in 13 million cases of ICC averted in LMICs and an incidence of ICC less than 4 per 100,000 women worldwide. Robust literature and extensive modeling show us that HPV vaccination is effective in preventing infection with the virus, cervical precancers, ICC, and with the help of biomedical and policy innovation; the near elimination of cervical cancer is possible in countries with robust uptake of the vaccine.

Amphipathic barbiturates as marine product mimics with cytolytic and immunogenic effects on head and neck squamous cell carcinoma cell lines.

The incidence of head and neck squamous cell carcinoma (HNSCC) is increasing and the conventional treatments for this form of cancer can be tough. Despite the success of existing immunotherapies in some HNSCC patients, many do not respond to this type of treatment. Thus, the development of novel anti-cancer therapies should be prioritized. In the current study, the anticancer activity of a panel of novel compounds, herein termed marine product mimics (MPMs), against HNSCC cell lines is explored. The previously reported compound MPM-1, which is structurally related to the novel MPMs, was shown to have promising effects on the HNSCC cell line HSC-3. The results from the current study indicate that the novel MPMs are more potent than MPM-1 but cause a similar type of cell death. The results indicated that the MPMs must cross through the cell membrane to exert their action and that they are lysosomotropic. Further experiments showed that some of the MPMs could induce phosphorylation of eukaryotic initiation factor 2α (eIF2α) in HSC-3 and UT-SCC-24A cells, which indicates that they can activate the integrated stress response that is strongly associated with immunogenic cell death. Cell surface expression of calreticulin and release of HMGB1 and ATP, which are all hallmarks of immunogenic cell death, was also demonstrated in HSC-3 and UT-SCC-24A cells treated with MPMs. This suggests that the MPMs are interesting candidates for future HNSCC cancer therapies.

Temporal increase in the incidence of anal squamous cell carcinoma in Kentucky and factors associated with adverse outcomes.

Anal squamous cell cancer (ASCC) incidence in Kentucky is increasing at an alarming rate. In 2009, the incidence surpassed the US national average (2.66 vs. 1.77/100,000 people), and currently, Kentucky ranks second by state per capita. The reasons for this rise are unclear. We hypothesize individuals with ASCC in Kentucky have some unique risk factors associated with worse outcomes. Individuals with ASCC in a population-level state database (1995-2016), as well as those treated at two urban university-affiliated tertiary care centers (2011-2018), were included and analyzed separately. We evaluated patient-level factors including demographics, tobacco use, stage of disease, HIV-status, and HPV-type. We evaluated factors associated with treatment and survival using univariable and multivariable survival analyses. There were 1698 individuals in state data and 101 in urban center data. In the urban cohort, 77% of patients were ever-smokers. Eighty-four percent of patients had positive HPV testing, and 58% were positive for HPV 16. Seventy-two percent of patients were positive for p16. Neither smoking, HPV, nor p16 status were associated with disease persistence, recurrence-free survival, or overall survival (all p > 0.05). Poorly controlled HIV (CD4 count <500) at time of ASCC diagnosis was associated disease persistence (p = 0.032). Stage III disease (adjusted HR = 5.25, p = 0.025) and local excision (relative to chemoradiation; aHR = 0.19, p = 0.017) were significantly associated with reduced recurrence-free survival. The rate of ASCC in Kentucky has doubled over the last 10 years, which is outpacing anal SCC rates in the US with the most dramatic rates seen in Kentucky women. The underlying reasons for this are unclear and require further study. There may be other risk factors unique to Kentucky.

The effect of statin medication on the incidence of oral squamous cell carcinoma among betel-nut chewers.

This study examines the relationship between statin use and oral cancer squamous cell carcinoma (OCSCC) risk in a cohort of 47 942 betel nut chewers. The study used individual 1:1 matching and propensity score matching to compare statin users and nonusers. The incidence rate of OCSCC was significantly lower in statin users compared to nonusers (17.12 vs. 26.75 per 10 000 person-years), yielding an incidence rate ratio of 0.64. After adjusting for confounders, statin use was associated with a reduced risk of OCSCC (adjusted hazard ratio: 0.61; 95% confidence interval: 0.52-0.71). A dose-response relationship was observed, with a significant reduction in OCSCC incidence when the cumulative defined daily dose of statin use was equal to or greater than Q3. The risk of OCSCC was lower among users of both hydrophilic and lipophilic statins. This study provides evidence that statin use is associated with a reduced risk of OCSCC in betel nut chewers.

Updated racial disparities in incidence, clinicopathological features and prognosis of hypopharyngeal squamous carcinoma in the United States.

This study was to determine the racial disparities in incidence, clinicopathological features and prognosis of hypopharyngeal squamous cell carcinoma (HPSCC) in the US. The National Program of Cancer Registries and Surveillance, Epidemiology, and End Results (SEER) database was used to determine racial disparity in age adjusted incidence rate (AAIR) of HPSCC and its temporal trend during 2004-2019. Using the separate SEER 17 database, we further evaluated racial disparity in clinicopathological features, and in prognosis using Kaplan-Meier curves and Cox proportional hazard models. HPSCC accounted for 95.8% of all hypopharyngeal cancers and occurred much more frequently in males. Its incidence decreased in both male and females, in male non-Hispanic white (NHW), non-Hispanic black (NHB) and Hispanic as well as female NHW and NHB during the study period. NHB had the highest, whereas non-Hispanic Asian or Pacific Islanders (API) had comparable and the lowest incidence in both males and females. Among 6,172 HPSCC patients obtained from SEER 17 database, 80.6% were males and 83.9% were at the advanced stages III/IV. Five-year cancer specific and overall survival rates were 41.2% and 28.9%, respectively. NHB patients were more likely to be younger, unmarried, from the Southern region, larger sized tumor, and at the stage IV, but less likely to receive surgery. They also had higher proportions of dying from HPSCC and all causes. Multivariate analyses revealed that NHB with HPSCC at the locally advanced stage had both significantly worse cancer specific and overall survival compared with NHW, but not at early stage (I/II) or distant metastatic stage. Hispanic patients had significantly better prognosis than NHW at locally advanced and metastatic stages. NHW and API had comparable prognoses. HPSCC displays continuously decreased incidence and racial disparity. The majority of the disease is diagnosed at the advanced stage. NHB have the highest burden of HPSCC and a worse prognosis. More studies are needed to curtail racial disparity and improve early detection.

Human papilomaviru-related oropharyngeal squamous cell carcinoma and radiomics: A new era?

The increase of the incidence of human papillomavirus dependent oropharyngeal squamous cell carcinoma is alarming, although we have greatly progressed in the classification and staging of this disease. We now know that human papillomavirus related oropharyngeal squamous cell carcinoma is a sub-type of head and neck squamous cell carcinoma with favourable prognosis and good response to therapy that needs a proper system of classification and staging. Thus, in routine practice it is essential to test patients for the presence of human papillomavirus. The most popular technique to assess human papillomavirus status is immunohistochemistry on biopsy samples with p16, which is an excellent surrogate for high-risk human papillomavirus infection. Another highly sensitive and specific tissue-based technique for the detection of human papillomavirus is RNAscope In situ hybridization that has a prohibitive cost, limiting its use in routine practice. Radiomics is an artificial intelligence based non-invasive method of computational analysis of computed tomography, magnetic resonance imaging, positron emission tomography, and ultrasound images. In this review, we summarise the last findings of radiomics applied to human papillomavirus associated oropharyngeal squamous cell carcinoma. A growing body of evidence suggest that radiomics is able to characterise and detect early relapse after treatment, and enable development of tailored therapy of human papillomavirus positive oropharyngeal squamous cell carcinoma.