Previous Squamous Cell Carcinoma Research Articles

Cutaneous squamous cell carcinoma of head and neck region: A single center analysis of 1296 tumors with clinical characteristics, comorbidities, treatment, and sun-protection behavior.

Cutaneous squamous cell carcinoma (SCC) is the second most common non-melanoma skin cancer among Caucasians. We analyzed our data on tumors been treated between 2006 and 2016 at the Skin Cancer Center of an academic teaching hospital. Thousand hundred and ninety-four patients with 1296 SCC have been identified including 804 males (67.3%) and 390 females (32.7%). The mean age among females was significantly higher with (83.9 ± 7.9) years compared with males ([79.3 ± 8.1] years; P < .001). The most common tumor localizations were outer ears (n=227, 17.5%), scalp (216, 16.7%), and forehead (215, 16.6%). The majority of tumors was stage I. 31.9% of patients had previous SCC or Bowen's cancer, 29.1% had actinic keratoses. Major non-dermatological comorbidities were cardiovascular diseases and diabetes. SCC were treated by delayed Mohs surgery. First Mohs procedure resulted in R0 status in 83.9%. Most cases with R1 resection were located on nose and eyelids. For a subpopulation of patients (n=105), a structured questionnaire study evaluated changes in sun protection behavior after skin cancer. After the confirmed diagnosis of a cutaneous SCC concerns about harm to the skin by intense sunlight was reported by 78.4% (76) of participants, with 92.0% among females versus 73.6% among males. Eighty percent of females and 76.8% of males wanted to care more about sun-protection in the future, spend less time 84.0% (females) and 72.5% (males) in the sun, and adapt their leisure activities for a better sun protection in 92.0% (females) and 81.9% (males). Secondary prevention in males needs improvement.

Narrow-band imaging versus Lugol chromoendoscopy for esophageal squamous cell cancer screening in normal endoscopic practice: randomized controlled trial

Narrow-band imaging (NBI) is as sensitive as Lugol chromoendoscopy to detect esophageal squamous cell carcinoma (SCC) but its specificity, which appears higher than that of Lugol chromoendoscopy in expert centers, remains to be established in general practice. This study aimed to prove the superiority of NBI specificity over Lugol chromoendoscopy in the detection of esophageal SCC and high grade dysplasia (HGD) in current general practice (including tertiary care centers, local hospitals, and private clinics). This prospective randomized multicenter trial included consecutive patients with previous or current SCC of the upper aerodigestive tract who were scheduled for gastroscopy. Patients were randomly allocated to either the Lugol or NBI group. In the Lugol group, examination with white light and Lugol chromoendoscopy were successively performed. In the NBI group, NBI examination was performed after white-light endoscopy. We compared the diagnostic characteristics of NBI and Lugol chromoendoscopy in a per-patient analysis. 334 patients with history of SCC were included and analyzed (intention-to-treat) from 15 French institutions between March 2011 and December 2015. In per-patient analysis, sensitivity, specificity, positive and negative likelihood values were 100 %, 66.0 %, 21.2 %, and 100 %, respectively, for Lugol chromoendoscopy vs. 100 %, 79.9 %, 37.5 %, and 100 %, respectively, for NBI. Specificity was greater with NBI than with Lugol (P = 0.002). As previously demonstrated in expert centers, NBI was more specific than Lugol in current gastroenterology practice for the detection of early SCC, but combined approaches with both NBI and Lugol could improve the detection of squamous neoplasia.

Pseudocarcinomatous Squamous Hyperplasia Involving Bone: A Diagnostic Pitfall Mimicking Squamous Cell Carcinoma.

Pseudocarcinomatous squamous hyperplasia (PSH) within the bone is uncommon and closely mimics well-differentiated squamous cell carcinoma (SCC). It arises from cutaneous or mucosal surfaces and grows directly into the bone. This study analyzes a large series of PSH and discusses the clinicopathologic features that facilitate its distinction from SCC. Cases were identified from the surgical pathology files between 1985 and 2020. The 31 cases included 21 males, 9 females, 1 unknown sex; who were 20 to 87 years old (average: 59 y). Sites included mandible-17, maxilla-5, toes-4, and 1 case from finger, femur, tibia, ischium, and unknown. Fourteen patients had a history of SCC, 13 treated with resection and chemoradiation and developed infected osteoradionecrosis, 4-medication-related osteonecrosis, 3-peripheral vascular disease, and diabetes mellitus, 3-trauma, 3-osteomyelitis, 3-unknown, and 1-hematologic malignancy. All cases exhibited severe osteomyelitis and nests of reactive keratinizing squamous epithelium that matured towards the bone surface, lacked significant atypia, or mitotic activity but permeated the medullary cavity. Patients with previous SCC developed PSH after 2 months to 8 years (average: 4 y). Nineteen of 30 patients had follow-up (2 to 48 mo, average: 17 mo); 6 patients experienced repeated debridements over 2 months to 1 year; no patient developed SCC. PSH involving bone is infrequent, complicates severe osteomyelitis, and is often therapy related. The clinical findings are usually not concerning for malignancy, however, the histologic findings are an important diagnostic pitfall because they mimic SCC.

IMPORTANCE OF FOLLOW-UP FOR LIP SQUAMOUS CELL CARCINOMA: REPORT OF 2 CASES

Squamous cell carcinoma (SCC) is the most frequent type of oral cancer. Lip SCC is associated with UV exposure during occupational activities. The objective of this study is to present 1 case of second primary SCC and 1 case of dysplasia after previous SCC on the lower lip. Case 1: A 29-year-old male patient was diagnosed with SCC in the lower lip and was referred to the oncologist. After 4 and a half years, he returned with a moderate dysplasia. Case 2: A 63 year-old-male patient was diagnosed with SCC of the lip and received treatment. After 3 years, he returned with a new primary SCC on the opposite side of the lip. Usually patients with SCC on the lips present actinic cheilitis, which need to be periodically followed up to diagnose early potential new areas of SCC or dysplasia as illustrated in these reports.

Risk factors for development of new skin neoplasms in patients with past history of skin cancer: A survival analysis

We conducted a retrospective study aiming to assess the risk, and associated risk factors, of developing subsequent skin cancers after having a first diagnosis of skin cancer. We included all patients with biopsy-proven skin cancer attending a dermatology clinic between July 2007 and July 2017. We assessed the frequency of new skin cancers, as well as potential demographic and clinical factors significantly associated with occurrence of such neoplasms, that were identified by means of a survival analysis. We analyzed 969 patients with a total of 1584 skin neoplasms (1122 basal cell carcinomas (BCC), 310 squamous cell carcinomas (SCC), 143 melanomas and 9 other neoplasms). 165 patients (17.0%) developed subsequent skin neoplasms. Factors identified in multivariable models to be significantly associated with development of new skin cancers included older age (adjusted HR = 1.04 per year; 95%CI = 1.02–1.05; p < 0.001), and presence of synchronous neoplasms (adjusted HR = 2.25; 95%CI = 1.61–3.14; p < 0.001). Having a history of a BCC was significantly associated with development of new BCC (adjusted HR = 1.63; 95%CI = 1.05–2.54; p = 0.030), while having a previous SCC was associated with occurrence of subsequent SCC (adjusted HR = 3.60; 95%CI = 1.93–6.72; p < 0.001). These findings point to the importance of careful follow-up (e.g., skin self-examination and full body examination) of skin cancer patients.

Vitamin D status in adult patients with nonmelanoma skin cancer in Cape Town, South Africa: a cross-sectional study.

Ultraviolet (UV) radiation is the most important environmental risk factor for the development of nonmelanoma skin cancer (NMSC). UV radiation is, however, also vital in the formation of vitamin D in humans. Strict sun protection advised to skin cancer patients may lead to vitamin D deficiency, yet vitamin D may have a protective effect against cancer formation. The primary aim was to determine whether patients with nonmelanoma skin cancer at our institution were vitamin D deficient. 25-Hydroxyvitamin D (25[OH]D) levels were determined in 109 patients with a diagnosis of basal cell carcinoma (BCC) and/or squamous cell carcinoma (SCC) during the summer and winter of 2015 at the Tygerberg Academic Hospital in Cape Town, South Africa. Associations between clinical and epidemiological data and the 25(OH)D level results were investigated. Vitamin D deficiency was defined as total 25(OH)D levels <20 ng/mL (<50 nmol/L). It was found that 49.5% of NMSC patients were vitamin D deficient, and 41.3% had insufficient vitamin D levels. Females were more likely than males to be vitamin D deficient (P = 0.047). Winter was significantly associated with vitamin D deficiency, compared to summer (OR = 4.81, 95%CI = 2.09-11.09, P <0.001). Having a previous SCC appeared associated with not being vitamin D deficient (OR = 0.46, 95%CI = 0.20-1.11, P = 0.084). The findings highlight the need for the development of recommendations and guidelines on sun protection in patients with NMSC, while still ensuring an adequate vitamin D status. High risk factors included winter and female gender.

Risk of Aggressive Skin Cancers After Kidney Retransplantation in Patients With Previous Posttransplant Cutaneous Squamous Cell Carcinomas: A Retrospective Study of 53 Cases.

The course of skin cancer after retransplantation in organ-transplant recipients who have already developed posttransplant skin cancer has not been assessed. This retrospective multicentric study included 53 patients with a history of cutaneous squamous cell carcinoma (SCC) after a first kidney transplantation who received a second kidney transplantation. The primary endpoint was the occurrence of aggressive cutaneous SCC after the second transplantation. Secondary endpoints included the course of skin cancers over 3 periods (first transplantation, return to dialysis, second transplantation), the time to occurrence, and risk factors for aggressive SCC after retransplantation. The first SCC developed in 47 patients with a functional graft and in 6 after return to dialysis. After the first transplantation, 17 (33.3%) patients developed SCC in dialysis and 39 (73.6%) after the second transplantation, respectively. Twenty aggressive SCC developed over the study period. They occurred in 14 (26.4%) patients after retransplantation vs 5 (9.4%) after the first transplantation with a median delay of 50 months and were responsible for 5 deaths. Fair skin type, multiple tumors before retransplantation, treatment with azathioprine, T cell-depleting antibodies, and delayed revision of immunosuppression were associated with an increased risk of aggressive cutaneous SCC after retransplantation. Candidates to retransplantation with a history of posttransplant SCC have a high risk of aggressive SCC. Our data suggest that the risk could be reduced by a tailored immunosuppression. A wait period may be required depending on the clinicopathological characteristics of the previous SCC and discussed on an individual patient basis.

Sarcomatoid Carcinoma in Head and Neck

Sarcomatoid carcinoma (SaCa) is a rare variant of squamous cell carcinoma (SCC) with sarcomatoid features. This study investigated the clinical presentation and outcomes of head and neck SaCa. In addition, reconstructive outcome for a subset of patients was also evaluated. Seventy-eight SaCa cases including 72 men and 6 women were identified from 13,777 head and neck SCC cases. Clinical outcomes were evaluated based on locoregional control, distant metastases, and multivariate analyses. Reconstructive outcome was evaluated by flap survival rate. Of the 78 cases, 71% (55) of cases were located in the oral mucosa; 64% (50) of patients were classified as T3 or T4 at the time of diagnosis. The 5-year survival was only 16%. Multivariate analysis revealed better outcomes only when the patient had a history of previous SCC. Forty-five patients underwent flap reconstruction, with 98% flap survival rate but the functional result varied because of the inevitable adjuvant radiotherapy and advanced stage of tumor. Sarcomatoid carcinoma is a different entity from the conventional SCC of the head and neck. Sarcomatoid carcinoma carries a poorer prognosis despite aggressive surgical intervention and concurrent adjuvant therapies. It remains a great challenge for clinical oncologists, and the optimal treatment strategy requires further studies. Free flap is still preferred for defect reconstruction but the design should be simplified to avoid complications.

Characterization of Monocyte‐Derived Dendritic Cells from Immunosuppressed Renal Transplant Recipients with and without Squamous Cell Carcinomas

Renal transplant recipients (RTR) have a high risk of tumour development, especially cutaneous squamous cell carcinomas (SCC), due to long-term immunosuppressive therapy. RTR may develop multiple lesions over short time periods, and these are often more aggressive with a higher risk of local recurrence and metastasis resulting in increased morbidity and mortality in these patients. Therefore, we took the first step towards evaluating the possibility of generating a therapeutic vaccine based on monocyte-derived dendritic cells (moDC) for these patients. We analysed the phenotype and cytokine/chemokine profile of moDC from long-term immunosuppressed RTR with and without previous SCC. The number of peripheral blood mononuclear cells (PBMC) isolated per ml blood as well as the efficiency of generating moDC from peripheral blood mononuclear cells (PBMC) was similar in patients and immunocompetent controls. Phenotype and cytokine/chemokine profile of the moDC from immunosuppressed patients were similar to those from immunocompetent controls, making moDC-based immunotherapy a potential future treatment option for RTR with multiple SCC.

Two-Year Randomized Controlled Prospective Trial Converting Treatment of Stable Renal Transplant Recipients With Cutaneous Invasive Squamous Cell Carcinomas to Sirolimus

In light of the significant morbidity and mortality of cutaneous invasive squamous cell carcinomas (SCCs) in renal transplant recipients, we investigated whether conversion to sirolimus-based immunosuppression from standard immunosuppression could diminish the recurrence rate of these skin cancers. In a 2-year randomized controlled trial, 155 renal transplant recipients with at least one biopsy-confirmed SCC were stratified according to age (< 55 v ≥ 55 years) and number of previous SCCs (one to nine v ≥ 10) and randomly assigned to conversion to sirolimus (n = 74) or continuation of their original immunosuppression (n = 81). Development of a new SCC within 2 years after random assignment was the primary end point. After 2 years of follow-up, the risk reduction of new SCCs in the multivariable analysis was not significant, with a hazard ratio (HR) of 0.76 (95% CI, 0.48 to 1.2; P = .255), compared with a non-sirolimus-based regimen. After the first year, there was a significant 50% risk reduction, with an HR of 0.50 (95% CI, 0.28 to 0.90; P = .021) for all patients together and an HR of 0.11 (95% CI, 0.01 to 0.94; P = .044) for patients with only one previous SCC. The tumor burden of SCC was reduced during the 2-year follow-up period in those receiving sirolimus (0.82 v 1.38 per year; HR, 0.51; 95% CI, 0.32 to 0.82; P = .006) if adjusted for the number of previous SCCs and age. Twenty-nine patients stopped taking sirolimus because of various adverse events. Conversion to sirolimus-based immunosuppression failed to show a benefit in terms of SCC-free survival at 2 years.

Outcomes following transoral robotic surgery: Supraglottic laryngectomy

To describe a single center outcomes following transoral robotic surgery for supraglottic laryngectomy (TORS-SL). Prospective data collection. Patient records receiving TORS-SL for squamous cell carcinoma (SCCA) with at least 12 months follow-up fit inclusion for this study. Two patients with previous SCCA were excluded. 18 patients (14 male, 4 female) were included in the study, having a mean follow-up time of 28.1 months (SD = 12.1). All patients had negative margins confirmed on final pathology. Nine (50%) patients received postoperative chemoradiation therapy for advanced neck disease. No (0%) patients received tracheostomy or gastrostomy tubes. There were no (0%) local recurrences, and three (16.7%) regional recurrences. Five (27.8%) patients experienced temporary postoperative complications. Overall 2-year outcomes reached 83%, 100%, and 89% for locoregional control, disease-specific survival, and overall survival respectively. Initial outcomes for TORS-SL are encouraging and are comparable to previously described treatment modalities. Larger studies are encouraged.

Sirolimus and Secondary Skin-Cancer Prevention in Kidney Transplantation

BackgroundTransplant recipients in whom cutaneous squamous-cell carcinomas develop are at high risk for multiple subsequent skin cancers. Whether sirolimus is useful in the prevention of secondary skin cancer has not been assessed.MethodsIn this multicenter trial, we randomly assigned transplant recipients who were taking calcineurin inhibitors and had at least one cutaneous squamous-cell carcinoma either to receive sirolimus as a substitute for calcineurin inhibitors (in 64 patients) or to maintain their initial treatment (in 56). The primary end point was survival free of squamous-cell carcinoma at 2 years. Secondary end points included the time until the onset of new squamous-cell carcinomas, occurrence of other skin tumors, graft function, and problems with sirolimus.ResultsSurvival free of cutaneous squamous-cell carcinoma was significantly longer in the sirolimus group than in the calcineurin-inhibitor group. Overall, new squamous-cell carcinomas developed in 14 patients (22%) in the sirolimus group (6 after withdrawal of sirolimus) and in 22 (39%) in the calcineurin-inhibitor group (median time until onset, 15 vs. 7 months; P=0.02), with a relative risk in the sirolimus group of 0.56 (95% confidence interval, 0.32 to 0.98). There were 60 serious adverse events in the sirolimus group, as compared with 14 such events in the calcineurin-inhibitor group (average, 0.938 vs. 0.250). There were twice as many serious adverse events in patients who had been converted to sirolimus with rapid protocols as in those with progressive protocols. In the sirolimus group, 23% of patients discontinued the drug because of adverse events. Graft function remained stable in the two study groups.ConclusionsSwitching from calcineurin inhibitors to sirolimus had an antitumoral effect among kidney-transplant recipients with previous squamous-cell carcinoma. These observations may have implications concerning immunosuppressive treatment of patients with cutaneous squamous-cell carcinomas. (Funded by Hospices Civils de Lyon and others; TUMORAPA ClinicalTrials.gov number, NCT00133887.)

Mortality in cancer patients with a history of cutaneous squamous cell carcinoma - a nationwide population-based cohort study

BackgroundCutaneous squamous cell carcinoma (SCC) is associated with underlying immunosuppression, so it may be a prognostic marker in patients with subsequent cancer. We therefore conducted a nationwide population-based Danish cohort study to evaluate whether a history of cutaneuos SCC has prognostic impact in patients with one of the following index cancers: non-Hodgkin's lymphoma (NHL), or cancer of the lung, colon, rectum, breast, or prostate.MethodsWe used Danish medical databases, which cover the entire Danish population of 5.6 million inhabitants and linked them using the unique personal identification number assigned to all Danish residents. From 1982 through 2003, we identified 745 index cancer patients with and 79,143 without previous cutaneous SCC. Using Cox proportional hazards regression, we calculated adjusted mortality rate ratios (MRRs) with 95% confidence intervals (CIs).ResultsOverall, previous SCC was associated with an increased mortality of cancer (MRR 1.13, 95% CI: 1.04-1.23). When examining index cancers separately, increased MRRs were found for cancer of the lung (MRR 1.23, 95% CI: 1.05-1.43), colon (MRR 1.13, 95% CI: 0.92-1.40), rectum (MRR 1.29, 95% CI: 1.00-1.67), breast (MRR 1.09, 95% CI: 0.82-1.43), and NHL (MRR 1.09, 95% CI: 0.81-1.47), but not for prostate cancer (MRR 0.99, 95% CI: 0.83-1.18).ConclusionsOur results suggest that previous cutaneous SCC is associated with poor prognosis of some cancers. This finding stresses the importance of adherence to the existing recommendations of screening, diagnosis, and treatment of cancer in patients with a history of SCC.

Seropositivity for human papillomavirus and incidence of subsequent squamous cell and basal cell carcinomas of the skin in patients with a previous nonmelanoma skin cancer

Infection with human papillomaviruses (HPVs) is a risk factor for several epithelial cancers, but its relationship with keratinocyte tumours has not yet been established. Objective In this prospective study we investigated the possible role of different HPVs in the incidence of a subsequent nonmelanoma skin cancer (NMSC). One hundred and fifty-three patients with squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) enrolled in a previous case-control study were re-contacted, and a follow-up visit was offered. Demographic and clinical data, date of first NMSC presentation, Fitzpatrick skin type and history of NMSC during the follow-up period were ascertained. Recurrences and new second cancers were considered together as 'outcomes' in time-to-event analyses and in Cox proportional hazard models. Clinical data were obtained in 107 patients. HPV seropositivity at baseline was strongly associated with the risk of developing a second SCC after 5 years for a number of beta and gamma HPV types. For example, HPV-24-seropositive patients with an SCC at baseline had a 4-fold increased risk of developing a subsequent SCC (hazard ratio 4·35, 95% confidence interval 1·2-15·6, P = 0·024). No association between serological status for any HPV type tested and an increased risk of BCC was found. We observed a consistent pattern of a positive association between seropositivity for beta and gamma HPV types and the risk of a subsequent SCC in patients with a previous SCC. Our data corroborate the results of previous case-control studies and may spur further prospective studies on the causal role of HPVs in NMSC.

A Case–Control Study of Betapapillomavirus Infection and Cutaneous Squamous Cell Carcinoma in Organ Transplant Recipients

We examined the association between betapapillomavirus (betaPV) infection and cutaneous squamous cell carcinoma (SCC) in organ transplant recipients. A total of 210 organ transplant recipients with previous SCC and 394 controls without skin cancer were included. The presence of 25 betaPV types in plucked eyebrow hairs was determined using a human papillomavirus (HPV) DNA genotyping assay, and antibodies for the 15 most prevalent betaPV types were detected using multiplex serology. We used multivariate logistic regression models to estimate associations between various measures of betaPV infection and SCC. BetaPV DNA was highly prevalent (>94%) with multiple types frequently detected in both groups. We found a significant association between SCC and the concordant detection of both antibodies and DNA for at least one betaPV type (adjusted OR 1.6; 95% CI 1.1;2.5). A borderline-significant association with SCC was found for HPV36 (adjusted OR 2.4; CI 1.0;5.4), with similar associations for HPV5, HPV9 and HPV24. These data provide further evidence of an association between betaPV infection and SCC in organ transplant recipients. Confirmation of a betaPV profile predictive of risk for SCC may pave the way for clinically relevant pretransplant HPV screening and the development of preventive and therapeutic HPV vaccination.

Immune phenotype of peripheral blood cells and skin squamous cell carcinoma in organ transplant recipients

Evaluation of: Carroll RP, Segundo DS, Hollowood K et al. Immune phenotype predicts risk for posttransplantation squamous cell carcinoma. J. Am. Soc. Nephrol. 21, 713–722 (2010).Squamous cell carcinoma (SCC) of the skin is a common tumor in Caucasians, occurring on sun-damaged skin. The carcinogenesis of SCC is multifactorial and the most important risk factor is UV radiation. Interestingly, SCC is the most frequent malignancy following organ transplantation, with a 60–100-fold increased risk compared with the general population. Carroll et al. recently identified more than 35 FOXP3+ cells per µl and less than 100 natural killer cells per µl in peripheral blood and previous SCC as risk factors for SCC in renal transplant recipients. The ratio of CD8/FOXP3 cells was significantly lower in the microenvironment of SCC from kidney transplant recipients compared with immunocompetent patients. These findings provide hitherto unknown details about the potential influence of immunomodulation by drugs on the development of SCC in kidney transplant recipients. While this study population may not relate to all kidney transplant recipients, particularly those on other immunosuppressive regimens, Carroll et al. provide us with a tool to aid recognition of patients at a higher risk for SCC. Further studies will help to translate these findings into potentially useful tools for the dermatological management of kidney transplant recipients.

Squamous cell carcinoma of the tongue in a patient with Fanconi's anemia: a case report and review of the literature

Fanconi's anemia (FA) is an autosomal recessive disorder characterized by constitutional aplastic anemia and congenital abnormalities. Patients with this disorder are prone to develop leukemia. Besides the risk of squamous cell carcinoma (SCC), development especially in the head and neck region is also increased. Up to now 40 patients with FA have been reported to develop SCC, and in 14 of them the tongue was the primary site. All of the reported SCC in FA patients originated in mucosal and mucocutaneous sites, especially oral (n=25) and anogenital sites (n=8) and the esophagus (n=6), with the exception of two patients with multiple cutaneous involvement. We report a new case of SCC of the tongue in a patient with FA and review the previous SCC cases.