Squamous Cell Carcinoma Lesions Research Articles

Comparison of p16 with human papillomavirus with oral squamous cell carcinoma and oral premalignant lesion

Worldwide Oral carcinomas considerable problem. It is crucial to know the molecular incidences of molecular carcinogenesis, as it has a significant association with tobacco in Pakistani population. So, this study aimed to screen out the savage high risk of papilloma virus 16/18 and p16 in oral premalignant lesion and oral squamous cell carcinoma. Moreover, the p16 correlation between HPV and OPL and OSCC was also analyzed. Method: A total of 150 samples from the oral cavity were taken from the Hayatabad Medical complex (50 samples of OPL and 100 samples of OSCC).In this study we used immunohistochemistry to look for p16 in OPL and OSCC, and we used polymerase chain reaction to find HPV. SPSS 21 was used to input and evaluate the data. The relationship between HPVandp16withdifferentvariables was determined using Chi-square and Fisher exact tests. Results:For p16, 14% of 50 oral premalignant lesions were found positive and 86% were negative. Moreover, while screening for the OSCC, the 18 percent individuals were found positive for OSCC, while the remaining (82%) screened out negative. HPV was diagnosed in 6% of 50 OPL. The co-occurrence of HPV with p16 was found in all the 15 (100%) individual’s with a p value of 0.001. However, three of the 18 cases with p16 expression did not have HPV infection. Conclusion: The current research supports the use of p16 as a unique marker for human papilloma virus in oral squamous cell carcinomas. Furthermore, a chemical carcinogen like cigarettes is thought to be one of the main risk factors for p16 and HPV infection, as well as other things.

Expression and significance of mammalian target of rapamycin in cutaneous squamous cell carcinoma and precancerous lesions

ABSTRACT The aim of this study is to explore the role of mammalian target of rapamycin (mTOR) in cutaneous squamous cell carcinoma (CSCC), Bowen’s disease (BD), and actinic keratosis (AK) with squamous cell differentiation abnormality and its relationship with the degree of tumor proliferation. Thirty cases of clinical paraffin specimens of CSCC, BD, and AK were each collected from Jinhua Fifth Hospital, while 30 cases of normal skin specimens surgically resected in Department of Plastic Surgery were selected as controls. The expressions of mTOR and Ki-67 in tissues were detected by immunohistochemical staining. The positive expression rate of mTOR in the CSCC group was higher than those in the BD group and AK group (P < 0.05), while it was higher in the BD group and AK group than in the normal skin group (P < 0.05). The CSCC group had a higher positive expression rate of Ki-67 than the AK group (P < 0.01). The results of logistic regression analysis showed that the pathogenic site [odds ratio (OR) = 1.189, 95% confidence interval (95%CI): 1.028–1.381, P = 0.021], course of disease (OR = 2.059, 95%CI: 1.036–4.087, P = 0.043), and differentiation degree (OR = 1.325, 95%CI: 1.169–1.512, P = 0.001) were independent factors for the positive expression of mTOR. OR>1, indicating that the factor is a risk factor. The expression levels of mTOR in CSCC, BD, and AK were positively correlated with the expression level of Ki-67 (r = 0.827, P < 0.01, r = 0.608, P < 0.01, r = 0.368, P = 0.045). These results suggest that mTOR may be involved in the pathogenesis of CSCC, and related to the proliferation degree of CSCC, as an index reflecting the proliferation status of CSCC.

Complete response of advanced cutaneous squamous cell and basal cell carcinomas with sequential cemiplimab and sonidegib therapy

AbstractA 78‐year‐old woman was referred to our skin cancer centre with three previous incomplete resections in the left cavum conchae of a deep‐infiltrating locally advanced, but still asymptomatic basal cell carcinoma (BCC). The patient noted furthermore two rapidly growing exophytic lesions in the left preauricular and cervical area in the last weeks. The clinical and histological distinction of locally advanced from metastatic cutaneous squamous cell carcinoma (CSCC) lesions was challenging. Imaging analysis with CT scans showed, however, an involvement of the parotid gland as well as multiple small lymph node metastases. The interdisciplinary tumour board decision at our institution recommended a systemic treatment with the PD1‐antibody cemiplimab. After 13 cycles with cemiplimab at a dose of 350 mg intravenously every 3‐weeks, the patient showed a complete response of the two CSCC lesions with histological confirmation. However, the BCC of the left ear appeared to be unchanged and still asymptomatic. The interdisciplinary tumour board considered this tumour to be no candidate for a curative resection or irradiation. Therefore, the patient was exposed to the hedgehog inhibitor sonidegib with a conventional dose of 200 mg orally per day. After 3 months of treatment, the tumour showed a markable regression and a complete response was confirmed by 3‐punch biopsies from this preoperated lesion. Both cemiplimab and sonidegib were excellently tolerated with almost no adverse events apart from a mild fatigue (CTC grade 1) over the first 3 weeks of the cemiplimab therapy. There were no laboratory abnormalities found.

Combined Transcranial and Endoscopic Endonasal Approach for Resection of a Complex Sinonasal Squamous Cell Carcinoma: Two-Dimensional Operative Video.

Sinonasal squamous cell carcinoma (SCC) is a rare head-and-neck neoplasm that has a propensity to locally invade vital structures. Currently, the combination of surgical resection and radiation remains the optimal treatment. 1 However, the extent of disease burden and involvement of surrounding anatomy may make these inoperable. Here, we demonstrate the successful application of multidisciplinary approach for surgical resection of a large, complex SCC lesion centered at the superior nasal cavity with extension into the eye orbits and brain. A two-step approach was performed; transcribiform, endoscopic piecemeal resection with reconstruction of the skull base, followed by a bifrontal craniotomy. Reconstruction was achieved using an inlay of DuraMatrix allograft (Stryker Inc., Kalamzoo, Michigan, United States) followed by an inlay of AlloDerm (Allergan Inc., Irvine, California, United States), anchored anteriorly and posteriorly with wide wings placed over the respective orbital roofs. Major steps include (1) a summary of the patient presentation and preoperative imaging, (2) resection of the tumor endonasally, (3) resection of the tumor intracranially from a bifrontal craniotomy, and (4) a review of the postoperative imaging. The patient tolerated the procedure ( Fig. 1 ) well, returned to his baseline with no new neurologic deficits, and was placed on 6-week antibiotics regimen for osteomyelitis discovered during the operation. Approximately, 2 months after discharge, the patient unfortunately returned with altered mental status, was found to have sepsis, and expired shortly thereafter. This operative video illustrates the technical steps and capabilities of surgical treatment, achieving near-complete gross total resection of a complex SCC lesion using a multidisciplinary approach. The link to the video can be found at: https://youtu.be/8ffckKIuBzM .

Integrin αvβ6 as a Target for Tumor-Specific Imaging of Vulvar Squamous Cell Carcinoma and Adjacent Premalignant Lesions.

Simple SummaryVulvar tumors are sometimes difficult to distinguish from adjacent healthy tissue during surgery, causing recurrence rates of up to 40% and co-morbidity. Fluorescence-guided surgery illuminating neoplastic tissue is increasingly being used to assist surgeons for various types of cancers. As no suitable tracers are known yet for vulvar tumors, we have evaluated which proteins could be targeted for fluorescence-guided surgery. Immunohistochemistry was used to study the distribution of nine membrane proteins in healthy and (pre)malignant tissues that were consequently analyzed using quantitative image analysis. Integrin αvβ6 allowed for the most robust discrimination of VSCCs and adjacent premalignant lesions compared with surrounding healthy tissue. The use of an αvβ6 targeted near-infrared fluorescent probe for FGS of vulvar (pre)malignancies should be evaluated in future studies.Surgical removal of vulvar squamous cell carcinoma (VSCC) is associated with significant morbidity and high recurrence rates. This is at least partially related to the limited visual ability to distinguish (pre)malignant from normal vulvar tissue. Illumination of neoplastic tissue based on fluorescent tracers, known as fluorescence-guided surgery (FGS), could help resect involved tissue and decrease ancillary mutilation. To evaluate potential targets for FGS in VSCC, immunohistochemistry was performed on paraffin-embedded premalignant (high grade squamous intraepithelial lesion and differentiated vulvar intraepithelial neoplasia) and VSCC (human papillomavirus (HPV)-dependent and -independent) tissue sections with healthy vulvar skin as controls. Sections were stained for integrin αvβ6, CAIX, CD44v6, EGFR, EpCAM, FRα, MRP1, MUC1 and uPAR. The expression of each marker was quantified using digital image analysis. H-scores were calculated and percentages positive cells, expression pattern, and biomarker localization were assessed. In addition, tumor-to-background ratios were established, which were highest for (pre)malignant vulvar tissues stained for integrin αvβ6. In conclusion, integrin αvβ6 allowed for the most robust discrimination of VSCCs and adjacent premalignant lesions compared to surrounding healthy tissue in immunohistochemically stained tissue sections. The use of an αvβ6 targeted near-infrared fluorescent probe for FGS of vulvar (pre)malignancies should be evaluated in future studies.

309 Does Anaesthetic Type Effect Positive Excision Margin Rate for Non-Melanoma Skin Cancers?

Abstract Aim Australia has the highest incidence of Non-melanoma skin cancers (NMSC) in the world estimated to be 2448/100,000 population with the state of Queensland carrying the highest burden. Surgical excision is the primary treatment and makes up a large proportion of general surgical lists in regional Queensland where they are typically removed using either local anaesthetic (LA) alone, local anaesthetic and sedation (LAS), or general anaesthesia (GA). There is little in the literature to suggest if anaesthetic type effects the rate of involved margins. The purpose of this study is to establish if anaesthetic type impacts the rate of positive excision margins in regional hospitals in Queensland. Method A retrospective audit was performed, incorporating a total of 194 squamous and basal cell carcinoma lesions excised between October 2019 and October 2020 at two hospitals in regional Australia. Data was recorded for the type of anaesthetic used and the histopathology of the lesions including type of lesion and microscopic margin involvement. Results Of the 194 excised lesions 39 of them had involved margins (20.1%). The rate of involved margins under LA, GA and LAS were found to be 19.79%, 18.52% and 22.73% respectively. When comparing these modalities with each other: LA vs GA, LAS vs GA and LA vs LAS no significant difference was found in involved margins for excision of NMSC with p-values (&amp;lt;0.05) of 1, 0.624 and 0.8225 respectively. Conclusions Modality of anaesthetic used for excision of NMSC does not affect the outcome of margin involvement.

Role of FDG-PET CT in differentiating adenocarcinomas from squamous cell carcinomas of the lung

Abstract Background Lung cancer is the leading cause of cancer related deaths worldwide. The combination of fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) and computed tomography (CT) has a great impact on the diagnosis, staging, and hence on the treatment plan and follow up of lung cancer patients. Maximum standardized uptake value (SUVmax) is a semi-quantitative index which is easily performed and the most widely used quantitative parameter for the analysis of 18F-FDG PET images and for the estimation of metabolic activity. Objective to investigate the role of PET/ CT to differentiate between adenocarcinomas (AC) and squamous cell carcinomas (SCC) as the most common lung cancer by comparing their FDG uptake measured in the form of SUVmax. Methods A retrospective observational study, conducted at Ain Shams University Hospitals- Radiology Department patients diagnosed with non-small cell lung cancer (NSCLC) and histopathologically proved to be adenocarcinoma or squamous cell carcinoma. All were investigated using PET/CT scans in the period between June 2017 to September 2019. SUVmax of the lesion were measured and statistically analyzed compared with the histopathological type. Results A total of 30 patients were evaluated with the age ranging from 31 to 81 years old, the mean was 56.9 years (SD ± 11.53). Among them 25 patients (83.3%) were males and 5 patients (16.7%) were females. Out of the 30 NSCLC patients included in the study, 18 patients (60%) were histopathologically diagnosed as AC and 12 patients (40%) were histopathologically diagnosed as SCC. The mean SUVmax of the 30 NSCLC lesions was 15.02±8.4 (range: 2-32.8).The mean SUVmax of AC lesions was 12.4±7.55 (range: 2-32.8), while the mean SUVmax of SCC lesions was 18.95±8.3 (range: 3.7-30.77). The mean SUVmax of lesions in patients with SCC was significantly higher than that of patients with AC using Wilcoxon-Mann-Whitney test (P = 0.04). Conclusion SCC of the lung has higher SUVmax than AC of the lung and it can be used to differentiate between them using PET/CT.

282 Phosphoproteomic profiling of AKT-related changes in cutaneous squamous cell carcinoma identified DNA-dependent protein kinase (DNA-PK) and N-Myc downstream regulator 2 (NDRG2) as therapeutic vulnerabilities

Cutaneous Squamous Cell Carcinoma (SCC) represents ∼20% of all non-melanoma skin cancers. Whilst SCC lesions are generally low risk, metastases are associated with poor prognosis. SCC incidence is increasing, owing to an ageing population, greater UV exposure, and more patients receiving immunosuppressive treatments associated with organ transplants. Therefore, there is interest in identifying new biomarkers that may be used to track progression of the disease and to exploit as therapeutic vulnerabilities.

Loss of FAM83H promotes cell migration and invasion in cutaneous squamous cell carcinoma via impaired keratin distribution

BackgroundsFAM83H is essential for amelogenesis, but recent reports implicate that FAM83H is involved in the tumorigenesis. We previously clarified that TRIM29 binds to FAM83H to regulate keratin distribution and squamous cell migration. However, little is known about FAM83H in normal/malignant skin keratinocytes. ObjectiveTo investigate the expression of FAM83H in cutaneous squamous cell carcinoma (SCC) and its physiological function. MethodsImmunohistochemical analysis and RT-PCR of human SCC tissues were performed. Next, we examined the effect of FAM83H knockdown/overexpression in SCC cell lines using cell proliferation, migration, and invasion assay. To investigate the molecular mechanism, immunoprecipitation of FAM83H was examined. Further, Immunofluorescence staining was performed. Finally, we examined the correlation between the expressions of FAM83H and the keratin distribution. ResultsFAM83H expression was lower in SCC lesions than in normal epidermis and correlated with differentiation grade. The mRNA expression levels of FAM83H in SCC tumors were also lower than in normal epidermis. The knockdown of FAM83H enhanced SCC cell migration and invasion, whereas the overexpression of FAM83H led to decreases in both. Furthermore, the knockdown of FAM83H enhanced the cancer cell metastasis in vivo. FAM83H formed a complex with TRIM29 and keratins. The knockdown of FAM83H altered keratin distribution and solubility. Clinically, the loss of FAM83H correlates with an altered keratin distribution. ConclusionOur findings reveal a critical function for FAM83H in regulating keratin distribution, as well as in the migration/invasion of cutaneous SCC, suggesting that FAM83H could be a crucial molecule in the tumorigenesis of cutaneous SCC.

820 EFFICACY AND SAFETY OF ENDOSCOPIC SUBMUCOSAL DISSECTION FOR SUPERFICIAL ESOPHAGEAL SQUAMOUS CELL CARCINOMA AND PRECANCEROUS LESIONS

Abstract With the development of endoscopic technology, endoscopic mucosal dissection (ESD) has become one of the standard treatments for superficial esophageal squamous cell carcinoma and precancerous lesion (SESCC-PL). However, the efficacy and safety of ESD in some special SESCC-PL patients is still unclear. The purpose of this study was to analyze the efficacy and safety of ESD in patients with SESCC-PL, especially for some special patients. Methods Firstly, according to the depth of lesions, all patients were divided into three groups: the epithelium and lamina propria group (M1-M2), the muscularis mucosae and submucosal superficial layer group (M3-SM1) and the submucosal deep layer group (≥SM2). Secondly, according to the age of patients, all patients were divided into two groups: elderly group (≥ 65 years old) and non-elderly group (&amp;lt;65 years old). Finally, all patients were divided into two groups: patients with liver cirrhosis group and patients without liver cirrhosis group. The efficacy and safety of ESD for these patients were analyzed. Results There was no significant difference in operation time, resection speed, en bloc resection rate, bleeding rate, muscularis propria injury rate, perforation rate and intraoperative esophageal stricture rate in three groups with different depths of lesion. However, the R0 resection rate among the three groups decreased with the increase of lesion depth (P &amp;lt; 0.001). There was no significant difference in all surgical indexes between the non-elderly group and the elderly group (all P &amp;gt; 0.05). And there was also no significant difference in all surgical indexes including bleeding rate between the patients with liver cirrhosis and without liver cirrhosis (all P &amp;gt; 0.05). Conclusion This study proved that ESD is safe and effective for all kinds of patients with SESCC-PL, especially for patients with lesion depth ≥ M3, elderly patients and patients with liver cirrhosis, ESD can still achieve a satisfactory treatment effect and a good survival prognosis. Liver cirrhosis is not a contraindication to ESD.

Metallothioneins and Megalin Expression Profiling in Premalignant and Malignant Oral Squamous Epithelial Lesions.

Simple SummaryInteractions of metallothioneins with the multiligand receptor megalin have been found to promote cell survival and proliferation after noxious stimuli in non-malignant tissues. However, the relationship between these proteins and their interaction remains to be addressed in malignancies and premalignant lesions. In this retrospective study, we compared the expression profiles of metallothioneins and megalin in different histological grades of oral squamous cell carcinoma, oral leukoplakia, and oral lichen planus. The data obtained show a gradual increase of both proteins concomitantly with the gaining of more malignant features, as well as their co-expression and direct interaction in carcinomatous tissue. The results point to the pro-oncogenic role of the metallothionein-megalin functional axis, which may impact tumor phenotype and behavior.This study aimed to assess the relationship and possible interactions between metallothioneins (MTs) and megalin (LRP-2) in different grades of oral squamous cell carcinoma (OSCC) and premalignant lesions of the oral mucosa (oral leukoplakia and oral lichen planus). The study included archived samples of 114 patients and control subjects. Protein expression was examined by immunohistochemistry and immunofluorescence, and staining quantification was performed by ImageJ software. Protein interaction in cancer tissue was tested and visualized by proximity ligation assay. Mann-Whitney and Kruskal-Wallis tests were used to determine the significance of differences between each group, whereas Pearson correlation coefficient was performed to test correlation. Expression of both proteins differed significantly between each group showing the same pattern of gradual increasing from oral lichen planus to poorly differentiated OSCC. Moreover, MTs and megalin were found to co-express and interact in cancer tissue, and their expression positively correlated within the overall study group. Findings of prominent nuclear and chromosomal megalin expression suggest that it undergoes regulated intramembrane proteolysis upon MTs binding, indicating its ability to directly affect gene expression and cellular division in cancer tissue. The data obtained point to the onco-driving potential of MTs-megalin interaction.

Comprehensive Analysis of circRNA Expression Profiles During Cervical Carcinogenesis.

Circular RNAs (circRNAs) are regulatory molecules that participate in the occurrence, development and progression of tumors. To obtain a complete blueprint of cervical carcinogenesis, we analyzed the temporal transcriptomic landscapes of mRNAs and circRNAs. Microarrays were performed to identify the circRNA and mRNA expression profiles of cervical squamous cell carcinoma (CSCC) and high-grade squamous intraepithelial lesion (HSIL) patients compared with normal controls (NC). Short time-series expression miner (STEM) was utilized to characterize the time-course expression patterns of circRNAs and mRNAs from NC to HSIL and CSCC. A total of 3 circRNA profiles and 3 mRNA profiles with continuous upregulated patterns were identified and selected for further analysis. Furthermore, functional annotation showed that the mRNAs were associated with DNA repair and cell division. The protein-protein interaction (PPI) network analysis revealed that the ten highest-degree genes were considered to be hub genes. Subsequently, a competing endogenous RNA (ceRNA) network analysis and real-time PCR validation indicated that hsa_circ_0001955/hsa-miR-6719-3p/CDK1, hsa_circ_0001955/hsa-miR-1277-5p/NEDD4L and hsa_circ_0003954/hsa-miR-15a-3p/SYCP2 were highly correlated with cervical carcinogenesis. Silencing of hsa_circ_0003954 inhibited SiHa cell proliferation and perturb the cell cycle in vitro. This study provides insight into the molecular events regulating cervical carcinogenesis, identifies functional circRNAs in CSCC, and improves the understanding of the pathogenesis and molecular biomarkers of CSCC and HSIL.

Evaluation of Depth of Invasion in Oral Squamous Cell Carcinoma with Ultra-High Frequency Ultrasound: A Preliminary Study

Intraoral ultrasonography has been widely employed for the preoperative assessment of tumor margins due to its capability to evaluate depth of invasion (DOI) and tumor thickness (TT). Recently, a novel ultrasonographic technique, ultra-high frequency ultrasound (UHFUS) has been increasingly applied to the study of oral lesions. This study evaluates the potential application of intraoral UHFUS to assess DOI and TT parameters of oral squamous cell carcinoma (OSCC) lesions. Patients clinically suspected of OSCC lesions were enrolled and underwent an intraoral UHFUS examination preoperatively. The parameters of TT, DOI, echogenicity, and vascularization were assessed. The parameters of TT and DOI as evaluated by means of UHFUS were compared to histology, which was set as the benchmark. Ten patients in total were enrolled. UHFUS-based DOI and TT measurements were found to positively correlate with histology (p &lt; 0.05), although UHFUS provided a slight overestimation of DOI. No differences were found in terms of echogenicity or vascularization depending on the site of the lesion. According to these preliminary results, UHFUS could support the preoperative assessment of TT and DOI, potentially enhancing the clinical evaluation of OSCC.

Characterization of Permeability Barrier Dysfunction in a Murine Model of Cutaneous Field Cancerization Following Chronic UV-B Irradiation: Implications for the Pathogenesis of Skin Cancer.

Simple SummaryIn the present work, we developed an experimental preclinical model of skin with cutaneous field cancerization after chronic UV-B light exposure in an immunologically intact mouse model (SKH1 aged mice). We observed impairments in the transepidermal water loss, stratum corneum hydration, and surface pH. We also detected a marked hyperkeratotic hyperplasia of the epidermis, induction of keratinocyte hyperproliferation, incidental actinic keratosis, and in situ squamous cell carcinomas in the UV-B light-irradiated groups. In this context, the association between the permeability barrier impairment and keratinocyte hyperproliferation might be considered a new target in the management of skin with cutaneous field cancerization. As current therapeutic approaches to actinic keratosis and cutaneous field cancerization only focus on the direct antineoplastic, immunomodulatory, or photodynamic effects of approved topical drugs, this mouse model of skin with cutaneous field cancerization might be helpful for both the identification and screening of potentially new preventive strategies or treatments (e.g., skin barrier therapies).Chronic ultraviolet B (UV-B) irradiation is known to be one of the most important hazards acting on the skin and poses a risk of developing photoaging, skin with cutaneous field cancerization (CFC), actinic keratosis (AKs), and squamous cell carcinomas (SCCs). Most of the UV-B light is absorbed in the epidermis, affecting the outermost cell layers, the stratum corneum, and the stratum granulosum, which protects against this radiation and tries to maintain the permeability barrier. In the present work, we show an impairment in the transepidermal water loss, stratum corneum hydration, and surface pH after chronic UV-B light exposure in an immunologically intact mouse model (SKH1 aged mice) of skin with CFC. Macroscopic lesions of AKs and SCCs may develop synchronically or over time on the same cutaneous surface due to both the presence of subclinical AKs and in situ SCC, but also the accumulation of different mutations in keratinocytes. Focusing on skin with CFC, yet without the pathological criteria of AKs or SCC, the presence of p53 immunopositive patches (PIPs) within the epidermis is associated with these UV-B-induced mutations. Reactive epidermis to chronic UV-B exposure correlated with a marked hyperkeratotic hyperplasia, hypergranulosis, and induction of keratinocyte hyperproliferation, while expressing an upregulation of filaggrin, loricrin, and involucrin immunostaining. However, incidental AKs and in situ SCC might show neither hypergranulosis nor upregulation of differentiation markers in the upper epidermis. Despite the overexpression of filaggrin, loricrin, involucrin, lipid enzymes, and ATP-binding cassette subfamily A member 12 (ABCA12) after chronic UV-B irradiation, the permeability barrier, stratum corneum hydration, and surface pH were severely compromised in the skin with CFC. We interpret these results as an attempt to restore the permeability barrier homeostasis by the reactive epidermis, which fails due to ultrastructural losses in stratum corneum integrity, higher pH on skin surface, abundant mast cells in the dermis, and the common presence of incidental AKs and in situ SCC. As far as we know, this is the first time that the permeability barrier has been studied in the skin with CFC in a murine model of SCC induced after chronic UV-B irradiation at high doses. The impairment in the permeability barrier and the consequent keratinocyte hyperproliferation in the skin of CFC might play a role in the physiopathology of AKs and SCCs.

Primary periocular squamous cell carcinoma in central Spain: Factors related to recurrence.

To describe the characteristics and recurrence rates of primary periocular squamous cell carcinoma (SCC) in Spain. This retrospective study investigates the characteristics of primary periocular SCC at two tertiary centers in Spain from 2000 to 2020. Data were collected on demographics, skin phenotype, location, clinical and histological diagnosis, the commitment of surgical margins, recurrence, and risk factors. Multivariate analysis and risk factors were used to investigate recurrence rates, considering p < 0.05 as statistically significant. Over the 20-year studied period, 107 patients with primary periocular SCC were assessed. The mean age of SCC was 76.8 ± 12.8 years, 55 (50.9%) were females, and 105 (98.1%) had Fitzpatrick skin phenotype type II or III. SCC lesions affected less than 1/3 of the eyelid (56/52.3% cases), mainly the lower lid (42/39.3% lesions). Sixty (56.1%) cases were SCC differentiated, 76 (71%) had clear margins. Clinical diagnosis of SCC corroborated with histological in 84 (78.5%) cases and orbital involvement occurred in 18 (16.8%) cases. Recurrence was observed in 13 (12.1%) cases, occurring more in large tumors and undifferentiated subtype (53.8%), with committed margins (69.2%) (p = 0.001), being the commitment of margins a significant predictor for recurrence, although thickness was an independent predictor. Periocular SCC in Spain showed a similar pattern as in the world. The risk of recurrence is increased in undifferentiated and large periocular SCC, partially removed with committed margins.

Establishment of a Three-Dimensional In Vitro Model of Equine Papillomavirus Type 2 Infection.

There is growing evidence that equine papillomavirus type 2 (EcPV2) infection is etiologically associated with the development of genital squamous cell carcinoma (SCC) and precursor lesions in equids. However, the precise mechanisms underlying neoplastic progression remain unknown. To allow the study of EcPV2-induced carcinogenesis, we aimed to establish a primary equine cell culture model of EcPV2 infection. Three-dimensional (3D) raft cultures were generated from equine penile perilesional skin, plaques and SCCs. Using histological, molecular biological and immunohistochemical methods, rafts versus corresponding natural tissue sections were compared with regard to morphology, presence of EcPV2 DNA, presence and location of EcPV2 gene transcripts and expression of epithelial, mesenchymal and tumor/proliferation markers. Raft cultures from perilesional skin harboring only a few EcPV2-positive (EcPV2+) cells accurately recapitulated the differentiation process of normal skin, whilst rafts from EcPV2+ penile plaques were structurally organized but showed early hyperplasia. Rafts from EcPV2+ SCCs exhibited pronounced hyperplasia and marked dysplasia. Raft levels of EcPV2 oncogene transcription (E6/E7) and expression of tumor/proliferation markers p53, Ki67 and MCM7 expression positively correlated with neoplastic progression, again reflecting the natural situation. Three-dimensional raft cultures accurately reflected major features of corresponding ex vivo material, thus constituting a valuable new research model to study EcPV2-induced carcinogenesis.

PD-L1 Expression, T-lymphocyte Subpopulations and Langerhans Cells in Cutaneous Squamous Cell Carcinoma and Precursor Lesions.

The role of immune cells and PD-L1 in cutaneous squamous carcinogenesis is unclear. This study examines T-cell populations, Langerhans cells (LCs) and PD-L1 in invasive squamous cell carcinoma (inSCC), adjacent precursors and normal skin (NS) to investigate their participation in tumorigenesis. Cases of cutaneous inSCC with adjacent precursors (n=125) were selected. In situ SCC (isSCC) and actinic keratosis (AK) were observed in 53 and 123 cases, respectively, whereas NS was present in 123 lesions. Immunohistochemistry was performed for CD3, CD8, Foxp3, CD1a and PD-L1. T-cells, LCs and PD-L1 gradually increase during the evolution from AK to isSCC and inSCC, with statistical significance between all lesions, except for CD3+ and CD8+ cells between isSCC and inSCC. Epithelial PD-L1 expression correlates with tumor diameter and thickness. The progressive increase of T-cells, LCs and PD-L1 in cutaneous squamous carcinogenesis provides rationale for immunotherapy and identification of predictive biomarkers.

Myiasis in Neglected Cutaneous Squamous Cell Carcinoma of the Head and Neck: Review of Management and Current Protocol Recommendations.

To propose a first-aid management protocol for myiasis in neglected cutaneous squamous cell carcinoma (SCC) in the ED based on a recent literature review. PubMed. Inclusion criteria were all series and case reports of primary/secondary cutaneous SCC with myiasis of the head and neck, including orbital SCC cases, published after 2005. A total of 14 articles including 15 patients were included. Demographics, socioeconomic situation, site of the lesion, larvae species with bacterial suprainfection, and first-aid treatment options were discussed. Two representative cases are described. Large, ulcerated, necrotic, myiasis-burdened SCC lesions in the head and neck area present a challenge for treatment, and to date, no consensus regarding first-aid management exists. The authors' proposed four-pillar first-aid management scheme may be a valid option to rapidly improve wound condition through disinfection, pain relief, and malodor and discharge eradication as a bridge to surgery.

Sequential treatment from mandibulectomy to reconstruction on mandibular oral cancer - Case review II: mandibular anterior and the floor of the mouth lesion of basaloid squamous cell carcinoma and clear cell odontogenic carcinoma

Preoperative patient analysis for oral cancer involves multiple considerations that are based on multiple factors; these include TNM stages, histopathologic findings, and adjacent anatomical structures. Once the decision is made to excise the lesion, the margin of dissection and its extent should be considered along with the best form of reconstruction and airway management. Treatment methods include surgical resection, radiotherapy, and chemotherapy. Although the combined method of treatment is controversial, surgical resection is considered predominantly, and immediate reconstruction after surgical resection follows. The choice of treatment is dictated by the anticipated functional and esthetic results of treatment and also by the availability of a surgeon with the required expertise. Segmental mandibulectomy with primary reconstruction has been shown to have advantages in both functional and esthetic results. A 52-year-old male patient with basaloid squamous cell carcinoma of the floor of the mouth, and the anterior portion of the mandible was treated with surgical procedures that included segmental mandibulectomy with both supraomohyoid neck dissection (SOHND) at Levels I–III and mandible reconstruction with a left fibula free flap. A 55-year-old male patient with clear cell odontogenic carcinoma of the oral cavity underwent segmental mandibulectomy with both SOHND at Levels I–III and mandible reconstruction with a left fibula free flap. The purpose of this study was to review the anatomic and functional results of patients after immediate reconstruction with a fibula free flap following resection of carcinoma in the anterior portion of the mandible and floor of the mouth.

HPV-mediated anal squamous cell carcinoma and precancerous lesions in HIV positive patients.

3520 Background: Anal cancer affects over 8,000 patients per year in the United States and the incidence is increasing. A significant risk factor for anal cancer and precancerous lesions is human papilloma virus (HPV), with up to 90% of cases being associated with HPV infection. Another emerging risk factor is HIV co-infection. In the present study, we further address if CD4 count is a significant factor for driving higher-grade HPV-mediated anal squamous lesions in HIV/HPV co-infection patients with a single institution large cohort. Methods: A retrospective cohort of HPV-positive patients with anal biopsies was obtained from 2002-2020. Information on the grade of their anal lesion, HIV status, and CD4 count (cells/mm3) were collected. In patients with HIV, the most recent CD4 count up to one year prior to or one month after their biopsy was utilized in our analysis. Lesions were grouped into low grade squamous intraepithelial lesions (LSIL) and higher grade squamous intraepithelial lesions (HSIL), carcinoma in situ (CIS), or squamous cell carcinoma (SCC). The Center for Disease Control CD4 count levels to define HIV status were utilized in our sub-analyses. The distribution of lesion grades was compared between HIV-negative and -positive patients, and between HIV-negative and three subgroups of HIV-positive patients using the Fisher’s exact test. Results: Our cohort comprised of 3,354 total HPV-positive patients. 2,036 of these patients were HIV-negative and 1318 were HIV-positive. The proportion of higher grade lesions was significantly higher in HIV/HPV co-infected patients regardless of CD4 count (Table). The full cohort of HIV-positive patients had lower rates of LSIL (60.8% vs. 74.0%) and higher rates of higher-grade lesions (39.2% vs. 26.0%) (p&lt;0.001) compared to HIV-negative patients. The distribution of lesion grades was also significantly different between HIV-negative patients and all HIV-positive patient subgroups, with all subgroups having higher rates of higher-grade lesions than HIV-negative patients (all p&lt;0.001). Conclusions: Our data show that HIV-HPV co-infection is a risk factor for higher grade anal lesions, regardless of CD4 status. This suggests that CD4 count is not the only factor responsible for the increased risk of higher-grade anal lesions, as the groups of HIV-positive patients with CD4 counts between 200-499 and above 499 still had a higher rate of higher-grade lesions than HIV-negative patients. Further research into other HIV-related immunologic changes that increase risk for higher-grade HPV-driven anal lesions is warranted.[Table: see text]