Incidence and profile of skin cancers in patients following ultraviolet phototherapy without psoralens: A retrospective cohort study.

BACKGROUND: Psoralen + ultraviolet-A (PUVA) is associated with photocarcinogenesis. However, carcinogenic risk with other ultraviolet phototherapies remains unclear. OBJECTIVE: Evaluate whether phototherapy without psoralens increases skin cancer risk. METHODS: Retrospective cohort study of patients treated at a teaching-hospital phototherapy center (1977-2018). Skin cancer records were validated against pathology reports. Age-standardized incidence rates (ASIRs) of skin cancer were evaluated for gender, skin phototype, diagnosis, ultraviolet modality, anatomical site; and compared to provincial population incidence rates (2003). RESULTS: In total, 3506 patients treated with broadband-ultraviolet-B, narrowband-UVB and/or combined UVAB were assessed with a mean follow-up of 7.3 years. Majority of patients had psoriasis (60.9%) or eczema (26.4%). Median number of treatments was 43 (1-3598). Overall, 170 skin cancers (17 melanoma, 33 squamous cell carcinoma and 120 basal cell carcinoma) occurred in 79 patients. Patient-based and tumor-based ASIR of skin cancer was 149 (95% CI: 112-187)/100,000 and 264 (219-309)/100,000 person-years, respectively. There was no significant difference between tumor-based ASIRs for melanoma, squamous cell carcinoma, and basal cell carcinoma compared to the general population; or in phototherapy patients with-psoriasis or eczema; or immunosuppressants. No cumulative dose-response correlation between UVB and skin cancer was seen. LIMITATIONS: Treatment and follow-up duration. CONCLUSION: No increased risk of melanoma and keratinocyte cancer was found with phototherapy.

A cohort analysis of residential radon exposure and melanoma incidence in Switzerland.

Radon is a radioactive noble gas found in Earth's crust. It accumulates in buildings, and accounts for approximately half the ionizing radiation dose received by humans. The skin is considerably exposed to ionizing radiation from radon. We aimed to evaluate the association between residential radon exposure and melanoma and squamous cell carcinoma incidence. The study included 1.3 million adults (20 years and older) from the Swiss National Cohort who were residents of the cantons of Vaud, Neuchâtel, Valais, Geneva, Fribourg, and Ticino at the study baseline (December 04, 2000). Cases of primary tumours of skin (melanoma and squamous cell carcinoma) were identified using data from cantonal cancer registries. Long-term residential radon and ambient solar ultraviolet radiation exposures were assigned to each individual's address at baseline. Cox proportional hazard models with age as time scale, adjusted for canton, socioeconomic position, demographic data available in the census, and outdoor occupation were applied. Total and age specific effects were calculated, in the full population and in non-movers, and potential effect modifiers were tested. In total 4937 incident cases of melanoma occurred during an average 8.9 years of follow-up. Across all ages, no increased risk of malignant melanoma or squamous cell carcinoma incidence in relation to residential radon was found. An association was only observed for melanoma incidence in the youngest age group of 20-29 year olds (1.68 [95% CI: 1.29, 2.19] 100 Bq/m3 radon). This association was mainly in women, and in those with low socio-economic position. Residential radon exposure might be a relevant risk factor for melanoma, especially for young adults. However, the results must be interpreted with caution as this finding is based on a relatively small number of melanoma cases. Accumulation of radon is preventable, and measures to reduce exposure and communicate the risks remain important to convey to the public.

Epidemiological and clinical analysis of exposure-related factors in non-melanoma skin cancer: A retrospective cohort study.

BACKGROUND: The incidence of non-melanoma skin cancers (NMSCs) increased over last decades, probably due to environmental concerns or to the increase of frail patients with age related comorbidities. Currently, the relationship of increasing global skin cancer rates with increased ultraviolet radiations (UVRs) resulting from stratospheric ozone depletion, global warming, and air pollution from fossil-fuel combustion. AIMS: We conducted a retrospective epidemiological study including 546 NMSC patients managed at the Dermatology Unit of the Tor Vergata Hospital to highlight different trends of sun exposure or different comorbidities. METHODS: Descriptive and inferential statistical analyses were performed to evidence differences between continous variable and Spearman rank test for dicotomical variables. Charlson Comorbidity Index was calculated to obtain the 10-years survival rate in order to identify the mean comorbidity burden of our patients. RESULTS: Considering patients with comorbidities (73.81%), actinic keratoses (AKs) was the most frequent lesion. In patients with a history of previous melanoma, basal cell carcinoma (BCC) was predominant (ANOVA test, p < 0.05) with a statistically significant correlation (rho = 0.453; p < 0.01). Squamous cell carcinoma (SCC) showed a higher rate in arterial hypertension patients, followed by the chronic heart failure and hematologic neoplasms (60%, 29.7% and 32.1%, respectively) groups. Men were more affected than women, representing 61.54% of patients. Chronic sun exposure is directly correlated with SCC rho = 0.561; p < 0.01), whereas BCC correlated with a history of sunburns (rho = 0.312; p < 0.05). CONCLUSIONS: History of photo-exposition had an important role on NMSC development especially for work or recreational reasons. Sex, age, and presence of comorbidities influenced different NMSC types. BCC was more frequent in younger patients, associated with melanoma and sunburns. The presence of SCC is associated with older patients and the hypertension group. AKs were diagnosed predominantly in oldest men, with a chronic sun-exposure history, and hematologic neoplasms group.

Discrete prognostic implication of sarcopenia according to nutritional status in surgically treated patients with hypopharyngeal cancer.

BACKGROUND: Nutritional status and sarcopenia affects the prognosis of head and neck cancers including hypopharyngeal cancer. Hypopharyngeal cancer patients tend to exhibit sarcopenia, which is associated with poor treatment outcomes. This study aims to determine the correlation between nutritional status and sarcopenia, and their prognostic role in surgically treated hypopharyngeal cancer. MATERIALS AND METHODS: Patients who had been diagnosed with squamous cell carcinoma originating from the hypopharynx and underwent surgery between January 2009 and December 2019 were enrolled in this study. The median neutrophil-to-lymphocyte ratio and prognostic nutritional index (PNI) of the cohort were considered the cut-off values. Sarcopenia was evaluated by measuring skeletal muscle index (SMI) at the third lumbar vertebra. Clinical and serological factors predictive of survival outcomes were evaluated. RESULTS: Patients with high PNI showed better 5-year Overall survival (OS) (52.8% vs. 27.2%, p = 0.001) and disease-free survival (DFS) (59.6% vs. 44.6%, p = 0.033) than those with low PNI. Likewise, patients with low SMI showed worse 5-year OS (25.0% vs. 60.9%, p = 0.002) and DFS (42.4% vs. 68.7%, p = 0.034) than patients with high SMI. Among the patients with high PNI, those with sarcopenia displayed significantly worse OS than those with high SMI (78.0% vs. 34.4%, p = 0.049). High PNI with high SMI presented better overall (p = 0.010) and DFS (p = 0.055) than any other group. CONCLUSIONS: Both sarcopenia and PNI were associated with the prognosis of hypopharyngeal cancer. Considering that PNI and sarcopenia indicate the nutritional status, nutritional status may be a significant risk factor. Therefore, nutritional support that ameliorates sarcopenia may improve survival outcomes in surgically treated patients with hypopharyngeal cancer.

Complication of head and neck cancer: Carotid blowout syndrome.

Carotid blowout syndrome (CBS) is an uncommon but potentially life-threatening condition characterized by the spontaneous or traumatic rupture of the carotid artery in the neck. Oftentimes, CBS is due a loss of structural arterial integrity from local radiotherapy or surgical procedures. A vast majority of patients who develop CBS also have a previous diagnosis of head and neck cancer. Due to the specific patient population who develop CBS and its life-threatening nature, CBS should be a part of emergency physicians differential for those who present with a chronic neck wound or neurological symptoms in those with a previous head and neck cancer diagnosis. In this case report, a patient with a history of squamous cell carcinoma of the oropharynx who was treated with chemoradiation therapy, presented to the emergency department with spontaneous bleeding from an existing chronic wound on the left lateral neck. Conservative measures were taken including wound dressing, and the patient was discharged to see dermatology for biopsy of a suspected cancerous lesion. Once the chronic lesion was biopsied, the patient had to be immediately rushed to the operating room due to a brisk pulsatile bleeding from puncturing the carotid artery. Proper wound packing and an ultrasound of the neck for a proper diagnosis may have prevented the need for surgical intervention in this case. Although CBS is not common, complications can lead to death as seen in this case. Timely recognition and proper interventions are critical for preventing potentially fatal outcomes in those with CBS.

A pulmonary artery was embolized in a patient with an occluded pulmonary vein to manage massive hemoptysis.

BACKGROUND: Stenosis and obliteration of the pulmonary vein can be developed by multiple diseases and might cause hemoptysis. Traditional therapy including surgical procedure and conservative treatments might be inappropriate choices to manage massive hemoptysis. CASE PRESENTATION: A 64-year-old man, diagnosed with advanced stage IVA lung squamous cell carcinoma, presented with dyspnea and recurrent, massive hemoptysis. An initial contrast-enhanced computed tomography revealed a giant tumor in the left lung hilus and occlusion of the left superior pulmonary vein. Despite immediate selective bronchial artery embolization and simultaneous embolization of an anomalous branch of the internal thoracic artery, the massive hemoptysis continued. Subsequently, embolization of the left superior pulmonary artery was performed, achieving functional pulmonary lobectomy, which successfully treated the hemoptysis without relapse during a six-month follow-up. The patient continues to undergo cancer therapy and remains stable. CONCLUSIONS: This case successfully managed massive hemoptysis associated with lung cancer invasion into the pulmonary vein through functional pulmonary lobectomy via embolization of the corresponding pulmonary artery.

Clinical outcomes of endoscopic submucosal dissection for esophageal squamous cell carcinoma with esophageal varices: Multicenter retrospective study.

OBJECTIVES: Clinical outcomes of endoscopic submucosal dissection (ESD) for esophageal squamous cell carcinoma (ESCC) with esophageal varices (EVs) are obscure. We aimed to elucidate the clinical outcomes of ESD for ESCC with EVs in a multicenter, retrospective study. METHODS: We established a retrospective cohort of 30 patients with ESCC complicating EVs, who underwent ESD at 11 Japanese institutions. Rates of en bloc resection and R0 resection, procedure time, and adverse events were evaluated as indicators of the feasibility and safety of ESD. Additional treatment, recurrence, and metastasis of the lesions were evaluated as indicators of the long-term efficacy of ESD. RESULTS: Portal hypertension was caused by cirrhosis, of which alcohol was the most common cause. En bloc resection was achieved in 93.3% and R0 resection in 80.0% of the patients. The median procedure time was 92 min. Adverse events included a case of uncontrolled intraoperative bleeding leading to discontinuation of ESD and a case of esophageal stricture due to extensive resection. During the follow-up period of a median for 42 months, a patient with local recurrence and another patient with liver metastasis were observed. One patient died of liver failure after receiving chemoradiotherapy as an additional treatment after ESD. No patient died of ESCC. CONCLUSION: This multicenter, retrospective cohort study demonstrated the safety and efficacy of ESD for ESCC with EVs. Further studies are needed to establish appropriate treatment methods for EVs before ESD and additional treatments for patients with insufficient ESD.

Reconstruction with free jejunal flap in dystrophic epidermolysis bullosa complicated with hypopharyngeal cancer: A case report.

Epidermolysis bullosa (EB) encompasses a range of rare genetic dermatological conditions characterized by mucocutaneous fragility and a predisposition to blister formation, often triggered by minimal trauma. Blisters in the pharynx and esophagus are well-documented, particularly in dystrophic EB (DEB). However, there have been few reports of mucocutaneous squamous cell carcinoma (SCC) in the head and neck region, for which surgery is usually avoided. This report presents the first case of free jejunal flap reconstruction after total pharyngolaryngoesophagectomy for hypopharyngeal cancer in a 57-year-old patient with DEB. The patient with a known diagnosis of DEB had a history of SCC of the left hand and esophageal dilatation for esophageal stricture. PET-CT imaging during examination of systemic metastases associated with the left-hand SCC revealed abnormal accumulation in the hypopharynx, which was confirmed as SCC by biopsy. Total pharyngolaryngoesophagectomy was performed, followed by reconstruction of the defect using a free jejunal flap. A segment of the jejunum, approximately 15 cm in length, was transplanted with multiple vascular pedicles. The patient made an uneventful recovery postoperatively and was able to continue oral intake 15 months later with no complications and no recurrence of SCC in the head and neck region. While cutaneous SCC is common in DEB, extracutaneous SCC is relatively rare. In most previous cases, non-surgical approaches with radiotherapy and chemotherapy were chosen due to skin fragility and multimorbidity. In the present case, vascular fragility and mucosal damage of the intestinal tract were not observed, and routine vascular and enteric anastomoses could be performed, with an uneventful postoperative course. Our findings suggest that highly invasive surgery, including free tissue transplantation such as with a free jejunal flap, can be performed in patients with DEB.

Malignant wound aetiology, diagnosis and management: a case series and literature review.

OBJECTIVE: Malignant wounds develop when neoplastic cells invade the skin either locally or by lymphatic and haematogenous spread. They can present as hard-to-heal wounds and underlying causes include: primary skin cancer; metastasis of extracutaneous primary malignancy; malignant transformation of a hard-to-heal wound; iatrogenic injury; and cutaneous forms of cancers of non-skin origin. High clinical suspicion for a malignant wound should be confirmed with skin biopsy. The aim of this case series is to highlight a combination of both clinically clear cutaneous malignancies and not-so-obvious wounds caused by malignancy. METHOD: This case series examines patients with malignant wounds of varying aetiology and appearance. For each case, we explain the pathophysiology, atypical features, diagnostic approach and treatment. We also discuss types of wound biopsy and general wound management principles. RESULTS: Among the 11 cases analysed using descriptive statistics, median wound duration before presentation at our clinic was one year, while median age at presentation was 65 years. Our case series included the following diagnoses: cutaneous metastasis of invasive ductal carcinoma of the breast (n=2); cutaneous metastasis of colorectal adenocarcinoma (n=1); Marjolin's ulcer (n=1), basal cell carcinoma (BCC) (n=2), primary cutaneous squamous cell carcinoma (SCC) (n=1), metastatic malignant melanoma (n=1), cutaneous T-cell lymphoma (n=1), cutaneous angiosarcoma (n=1), Kaposi sarcoma (n=1) and recurrent tonsillar SCC with osteoradionecrosis (n=1); one case had both BCC and SCC. CONCLUSION: Punch and excisional biopsies were the most frequently used diagnostic techniques. Local wound therapy addressed bleeding, malodour, exudate, pain and infection. However, wound healing is usually achieved once the underlying malignancy is treated. In advanced or metastatic disease, palliative wound care aims to prevent exacerbation of existing wounds and focuses on patient comfort.

Homolateral Embolic Stroke After Emergency Ligation of the Common Carotid Artery to Stop Heavy Bleeding Caused by Carotid Blowout Syndrome.

Emergency common carotid artery (CCA) ligation for bleeding control during carotid blowout syndrome with consecutive embolic stroke has been reported rarely. The patient is a 70-year-old man, who was suffering from acute profuse bleeding from the left superior thyroid artery into the piriformis sinus, which was not controlled other than by ligation of the left CCA. The cause of the bleeding remained unclear but was suspected to be related to his history of being positive for squamous cell carcinoma of the left hypopharynx with ari and postcricoid infiltration, diagnosed at age 58. Squamous cell carcinoma was treated with local resection, chemotherapy (docetaxel, carboplatin, and cetuximab), and radiotherapy. Neurological examination 4 days after CCA ligation revealed multiple subacute embolic strokes in the territory of the left middle cerebral artery, macroangiopathy of the extra and intracranial cerebral arteries, and hypoplasia of the left vertebral artery. This case demonstrates that carotid blowout syndrome may require CCA ligation when external carotid artery ligation is not possible, and that ligation can be complicated by an asymptomatic embolic stroke.

Incidence and Risk Factors for Recurrence and Progression of HPV-Independent Vulvar Intraepithelial Neoplasia.

OBJECTIVES: Human papillomavirus (HPV)-independent vulvar intraepithelial neoplasia (VIN) is a rare yet aggressive precursor lesion of vulvar cancer. Our objectives were to estimate its long-term incidence, the risk of recurrent disease and progression to vulvar cancer, and risk factors thereof. MATERIALS AND METHODS: Patients with HPV-independent VIN between 1991 and 2019 in a selected region were identified from the Dutch Nationwide Pathology Databank (Palga). Data were collected from the pathology reports. Crude and European age-standardized incidence rates were calculated for 10-year periods. Kaplan-Meier analyses were performed to determine the cumulative recurrence and cancer incidence, followed by Cox regression analyses to identify associated risk factors. RESULTS: A total of 114 patients were diagnosed with solitary HPV-independent VIN without prior or concurrent vulvar cancer. The European age-standardized incidence rate increased from 0.09 to 0.69 per 100,000 women-years between 1991-2010 and 2011-2019. A cumulative recurrence and cancer incidence of 29% and 46% were found after 8 and 13 years of follow-up, respectively. Nonradical surgery was identified as the only independent risk factor for recurrent HPV-independent VIN. Risk factors associated with progression to cancer were increasing age and a mutant p53 immunohistochemical staining pattern. CONCLUSIONS: The incidence of detected HPV-independent VIN has substantially increased the last decade and the subsequent recurrence and vulvar cancer risks are high. Although HPV-independent VIN may present as a wide morphologic spectrum, surgical treatment should aim for negative resection margins followed by close surveillance, especially for p53 mutant lesions.

Guillain-Barré Syndrome as a paraneoplastic neurological disease of pulmonary adenocarcinoma and squamous cell carcinoma: A case report.

We present the case of a 69-year-old male who presented with profound weakness in the extremities. Remarkably, he lacked any identifiable precipitating factors preceding the onset of his illness. However, a diagnosis of Guillain-Barré syndrome (GBS) was established based on typical clinical symptoms, cerebrospinal fluid analysis, and neurological examination. During his hospitalization, an incidental discovery of lung cancer was made. Subsequent pathology confirmed adenocarcinoma and squamous cell carcinoma in the lungs. This case report serves to underscore the exceptional rarity of the simultaneous occurrence of lung cancer and GBS, renewing interest in investigating GBS as a potential paraneoplastic neurological syndrome. Keywords: Guillain-Barré syndrome, paraneoplastic neurological disease, pulmonary adenocarcinoma, squamous cell carcinoma.

Hydrochlorothiazide and increased risk of atypical fibroxanthoma and pleomorphic dermal sarcoma.

BACKGROUND AND OBJECTIVES: Previous work has demonstrated that hydrochlorothiazide (HCTZ) is a risk factor for squamous cell carcinomas (SCC) and basal cell carcinomas (BCC) due to pro-photocarcinogenic effects. Atypical fibroxanthoma (AFX) and pleomorphic sarcoma (PDS), both ultraviolet-induced cancers, display a rare but rising cutaneous tumor entity. This study aimed to evaluate if the use of HCTZ is higher in patients with AFX/PDS than in patients with SCC/BCC and subsequently may be a risk factor for AFX/PDS-development. PATIENTS AND METHODS: In a retrospective study of four German skin cancer centers, AFX/PDS cases and SCC/BCC controls were sex and age matched (1:3) over a time-period of 7 years (2013-2019) to evaluate the use of HCTZ, immunosuppressive medication, second malignancies, and presence of diabetes mellitus. RESULTS: Overall, 146 AFX/PDS and 438 controls (SCC/BCC) were included in the study. The use of HCTZ was significantly higher in patients with AFX/PDS (44.5%) compared to patients with SCC/BCC (25.3%). Additionally, the presence of diabetes mellitus was significantly higher in AFX/PDS patients. CONCLUSIONS: This study demonstrates a significantly higher use of HCTZ in patients with AFX/PDS compared to SCC/BCC. This result suggests that HCTZ may be a risk factor for AFX/PDS. Additionally, diabetes mellitus or its comorbidities may be associated with an increased risk for AFX/PDS.

Oral squamous cell carcinoma arising from areas of Graft-versus-host disease: A systematic review.

BACKGROUND: Graft-versus-host disease (GVHD) is an immune system reaction that occurs in patients with a history of hematopoietic stem cell transplantation (HSCT), in which the grafted donor's cells attack those of the host. The objective of this systematic review was to present a study on oral squamous cell carcinoma (OSSC) that developed from GVHD areas in patients undergoing HSCT. MATERIAL AND METHODS: An electronic search was conducted in the databases PUBMED, WEB OF SCIENCE, SCOPUS, MEDLINE and SCIENCE DIRECT, according to PRISMA guidelines. RESULTS: Of the 1582 results, 23 articles were included, resulting in 81 cases. The most common underlying disease for performing the transplant was Myeloid Leukemia (55.6%). The mean age was 39 years, with a predilection for males (64.2%). The tongue was the site of GVHD that most frequently underwent transformation to SCC (59.3%). The average time between transplantation and the development of GVHD was of approximately of 8 months, while the average period of development between transplantation and the development of OSCC was of approximately of 111 months. The most common treatment to GVHD was cyclosporine associated with corticosteroids. CONCLUSIONS: OSCCs arising from areas of GVHD present a different evolution from conventional oral carcinomas, since they affect younger patients, smoking and alcohol are not important etiological factors and finally because they present good prognosis, but further studies with larger number cases followed are needed to confirm our findings.

Squamous Cell Carcinoma of the Supraglottis Presenting as Hoarseness.

Hoarseness is a well-known condition in primary care offices, with over 1% of primary care visits secondary to this ailment.1 The most common causes are acute laryngitis (40%), functional dysphonia (30%), benign and malignant tumors (2.2 to 30%), neurogenic factors such as vocal cord paralysis (8%), physiological aging (2%), and psychogenic factors (2.2%). Most of these cases are secondary to viral infections and do not require antibiotics on most occasions. These viral infections subside after 1 to 2 weeks, and in the case of persistent hoarseness (above 4 weeks) the American Academy of Otolaryngology recommends direct visualization with a laryngoscopy before treatment with proton pump inhibitors, antibiotics, or steroids. Our patient presented with prolonged hoarseness (greater than eight weeks) but had a quick turn around time interval between primary care visit and laryngoscopy evaluation (less than 2 weeks). This led to her diagnosis and treatment with chemo and radiation therapy within three months of diagnosis with Squamous Cell Carcinoma of the Supraglottis. The Primary care physician serves as the number one point of visitation by sufferers of hoarseness. It is important that they are knowledgeable and up to date with recommendations and guidelines for managing this condition, as unwarranted delay can affect overall outcome on the part of the patient. This is especially important in patients such as ours with high risk factors including Nicotine dependence, alcohol use, asbestos exposure, and HPV infection.

La voix rauque est une condition bien connue dans les cabinets de soins primaires, avec plus de 1 % des visites en soins primaires dues à ce problème. Les causes les plus courantes sont la laryngite aiguë (40%), la dysphonie fonctionnelle (30 %), les tumeurs bénignes et malignes (2,2 à 30 %), les facteurs neurogènes tels que la paralysie des cordes vocales (8 %), le vieillissement physiologique (2 %) et les facteurs psychogènes (2,2 %). La plupart de ces cas sont dus à des infections virales et ne nécessitent pas d'antibiotiques dans la plupart des cas. Ces infections virales disparaissent après 1 à 2 semaines, et en cas de voix rauque persistante (plus de 4 semaines), l'American Academy of Otolaryngology recommande une visualisation directe avec une laryngoscopie avant le traitement par inhibiteurs de la pompe à protons, antibiotiques ou stéroïdes. Notre patiente présentait une voix rauque prolongée (plus de huit semaines), mais a bénéficié d'un délai rapide entre la visite en soins primaires et l'évaluation par laryngoscopie (moins de 2 semaines). Cela a conduit à son diagnostic et à son traitement par chimiothérapie et radiothérapie dans les trois mois suivant le diagnostic de carcinome épidermoïde du supraglotte. Le médecin de soins primaires est le premier point de visite pour les personnes souffrant de voix rauque. Il est important qu'ils soient informés et à jour des recommandations et des lignes directrices pour la prise en charge de cette condition, car un retard non justifié peut affecter le résultat global pour le patient. Ceci est particulièrement important chez les patients comme le nôtre présentant des facteurs de risque élevés, y compris la dépendance à la nicotine, la consommation d'alcool, l'exposition à l'amiante. MOTS-CLÉS: Laryngoscopie, Supraglotte, Larynx, Enrouement.

Acrokeratosis paraneoplastica (Basex syndrome) with trachyonychia preceding the diagnosis of squamous cell carcinoma of the lung.

Acrokeratosis paraneoplastica (Basex syndrome) is a rare paraneoplastic condition hallmarked by psoriasiform lesion development on acral surfaces, most often related to an underlying squamous cell carcinoma. Patients may also present with nail plate changes. Successful management of this condition can be accomplished by treating the underlying malignancy.

Estimating the Global Burden of Epstein-Barr Virus-Associated Gastric Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND & AIMS: Evidence suggests that a fraction of new gastric cancer cases may be etiologically associated with Epstein-Barr virus (EBV), a known carcinogenic agent. We aimed to systematically explore the proportion of EBV-positive gastric cancer. METHODS: We did a systematic review (PROSPERO CRD42020164473) from January 1990 to August 2021. For each country and geographical region with available data, pooled prevalence and corresponding 95% confidence intervals (CIs) of EBV in gastric tumors were calculated for 3 subtypes of gastric adenocarcinoma (conventional adenocarcinoma, lymphoepithelioma-like gastric carcinoma, and remnant/stump carcinoma). For conventional adenocarcinoma, prevalence ratios (PRs) were presented for sex, Lauren's classification, gastric cancer stage, and anatomical location of the stomach. RESULTS: In 220 eligible studies including over 68,000 cases of conventional gastric adenocarcinoma, EBV prevalence in tumor cells was 7.5% (95% CI, 6.9%-8.1%) and was higher in men compared with women (PR, 2.1; 95% CI, 1.9-2.4), in diffuse type compared with intestinal type (PR, 1.3; 95% CI, 1.1-1.5), and in the proximal region compared with the distal region (PR, 2.5; 95% CI, 2.0-3.1). There was no difference in EBV prevalence by gastric cancer stage. EBV prevalence was 75.9% (95% CI, 62.8%-85.5%) among lymphoepithelioma-like gastric carcinoma and 26.3% (95% CI, 22.2%-32.0%) among remnant or stump carcinoma. CONCLUSIONS: Assuming a causal association between EBV and gastric cancer, our findings, when applied to the GLOBOCAN 2020 gastric cancer incidence, suggest that primary prevention such as the development of an effective EBV vaccine might prevent 81,000 EBV-associated gastric cancer cases worldwide annually.

Infection pattern and immunological characteristics of Epstein-Barr virus latent infection in cervical squamous cell carcinoma.

Previous studies reported the association between Epstein-Barr virus (EBV) and cervical squamous cell carcinoma (CSCC), but its infection pattern and clinical significance unclear. This study aimed to comprehensively investigate the infection pattern, clinicopathology, outcomes, and immunology of this entity in central China. We evaluated a total of 104 untreated CSCC tumor tissue specimens using in situ hybridization for EBV-encoded small RNAs (EBERs), and by employing flowcytometry fluorescence hybridization for human papillomavirus (HPV) genotyping. The expression of EBV latency proteins and immune biomarkers was evaluated and quantified by immunohistochemistry. EBERs transcripts were detected in 21 (20.2%) cases overall (in malignant epithelial cells of 13 cases and in lymphocytes of 8 cases). EBV belonged to latency type I infection in CSCC. The high-risk (HR)-HPV was detected in all of EBV-positive CSCC, and the difference of detection rate of HR-HPV was significant when compared with EBV-negative CSCC (p = 0.001). The specific clinicopathology with increased frequency of advanced clinical stages, tumor-positive lymph nodes, neural invasion, and increased infiltration depth (all p value < 0.05) were observed in cases with EBV. However, EBV infection was found to have no impact on prognosis of patients with CSCC. Increased densities of forkhead box P3 (FoxP3)+-tumor infiltrating lymphocytes (TILs) (p = 0.005) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)+-TILs (p = 0.017) and higher expression of programmed cell death-1 (PD-1) (p = 0.002) and programmed cell death-1 ligand 1 (PD-L1) (p = 0.040) were associated with EBV latent infection in CSCC, and these immunological changes were more likely to be associated with the infection in lymphocytes rather than tumor cells. Moreover, in patients with HPV-positive CSCC, similar significant differences were still found. In conclusions, EBV-positive CSCC may have specific infection pattern and clinicopathology and can exhibit an immunosuppressive microenvironment dominated by Treg cells aggregation and immune checkpoint activation.

Extended human papillomavirus genotype distribution in cervical intraepithelial neoplasia and cancer: Analysis of 40 352 cases from a large academic gynecologic center in China.

Our aim was to conduct a large epidemiologic analysis of the distribution of human papilloma virus (HPV) genotypes associated with cervical neoplasias and cancers at a major Chinese gynecologic center. The pathologic database was searched for cervical histopathologic diagnoses with prior HPV genotyping from liquid cervical cytology specimens obtained ≤6 months before biopsy. HPV testing was performed by using the Tellgenplex HPV27 or YanengBio HPV23 genotyping assays. A total of 40 352 cases meeting study criteria were identified. High risk human papillomavirus (hrHPV) was detected in 94.1% of squamous cancers compared to in only 83.3% of cervical adenocarcinomas. The prevalence of multiple HPV infections was highest in cervical intraepithelial neoplasia 1 (CIN1) (33.8%) and decreased with increasing severity of squamous lesions. The distribution of HPV genotypes was similar between CIN1 and histopathologic-negative cases. HPV16 was one of the three most common hrHPV genotypes before all histopathologic abnormalities, ranging from 72.0% for cervical cancers, 38.7% for CIN2/3/AIS, 13.1% for CIN1, and 9.1% for biopsy-negative cases. HPV16 and HPV18 accounted for over 87.2% of detected hrHPV genotypes for all glandular intraepithelial neoplastic lesions and cancers, whereas squamous lesions did not show this pattern. 80.3% of cervical cancers were associated with genotypes covered by HPV16/18 vaccines and 89.6% with genotypes covered by 9-valent vaccination.

Exogenous hormone therapy and non-melanoma skin cancer (keratinocyte carcinoma) risk in women: a systematic review and meta-analysis.

Previous studies reported inconsistent results regarding the association between keratinocyte carcinoma (KC) and exogenous hormone therapy. This study aimed to investigate the association between the use of exogenous sex hormones and the risk of KC among women. The databases of PubMed, Ovid Medline, Cochrane, and Web of Science were searched until May 2023. A total of 5293 patients with KC and 106,424 controls were included for analysis. The meta-analysis indicated that oral contraceptives (OC) and hormonal replacement therapy (HRT) use were associated with an increased risk of squamous cell carcinoma (SCC) (OR/RR = 1.25, 95% CI 1.10 to 1.43, I2 = 41.6%, p = 0.080). Subgroup analysis showed that OC use increased the risk of SCC (OR/RR = 1.37, 95% CI 1.15 to 1.63), whereas no significant association was shown between HRT use and risk of SCC (OR/RR = 1.13, 95% CI 0.93 to 1.37). Additionally, OC and HRT use were linked to an increased risk of basal cell carcinoma (BCC) (OR/RR = 1.16, 95% CI 1.09 to 1.25, I2 = 30.1%, p = 0.188). Further subgroup analysis suggested both OC and HRT use were associated with an increased risk of BCC (OC: OR/RR = 1.13, 95% CI 1.01 to 1.25; HRT: OR/RR = 1.19, 95% CI 1.09 to 1.30). In conclusion, our findings support the hypothesis that the risk of KC among women may be affected by the use of exogenous hormones.