Survival Outcomes of BSCC Variant Compared with SCC of the Head and Neck: A Cross-Sectional SEER-Based Analysis

Survival Outcomes of BSCC Variant Compared with SCC of the Head and Neck: A Cross-Sectional SEER-Based Analysis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Survival Outcomes of BSCC Variant Compared with SCC of the Head and Neck: A Cross-Sectional SEER-Based Analysis Rim Wally, Ahmed Elkoumi, Maged Ahmed Mohamed, Moamen Mostafa Asla, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6189154/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose Basaloid squamous cell carcinoma (BSCC) is known as an aggressive variant of squamous cell carcinoma (SCC) with lower survival rates, mostly because of the increased incidence of distant metastases. Our objective was to provide an update on the clinicopathological presentation and prognosis of BSCC. Methods A total of 3,327 BSCC patients and 84,724 conventional-type SCC patients were identified via the Surveillance, Epidemiology, and End Results database. Clinicopathologic data were compared via chi-square analysis. Kaplan–Meier analysis was used to estimate overall survival (OS), and the independent effect of BSCC on OS was assessed via multivariate regression analysis. Results The oral cavity was the most common site for BSCC and SCC (45.3%). More BSCC patients presented with advanced-stage disease (87.8% vs. 79.3%, P < 0.001). Multivariate analysis revealed that OS was significantly better in the BSCC group when the tumours were located in the tonsils, followed by the oral cavity, oropharynx and nasopharynx. OS was also high in patients who underwent curative surgical, radiological or chemotherapy. It was worse for BSCC patients with hypopharyngeal tumours. Conclusions BSCC’s propensity for advanced-stage presentation was confirmed in this study. However, BSCC has a better prognosis than conventional-type SCC. Our analysis revealed a male predominance in BSCC, with a mean age of 60. However, males had a lower hazard of death in both samples. Both groups exhibited a predominant representation of white ethnicity. SEER database basaloid survival squamous cell carcinoma head and neck Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 1. Background Basaloid squamous cell carcinoma (BSCC) is a rare and aggressive histopathological variant of squamous cell carcinoma (SCC). BSCCs are characterized by both basal cell carcinoma and squamous cell carcinoma with poor prognoses and high rates of distant metastases. BSCC can occur at various anatomical sites. BSCC is most commonly associated with the upper aerodigestive tract, but it can also occur in other locations, such as the skin, anogenital region and lungs. In the head and neck region, BSCC occurs in the larynx, hypopharynx, and base of the tongue ¹-³. Like other types of squamous cell carcinoma, risk factors for BSCC may include exposure to ultraviolet radiation, tobacco use, alcohol consumption, and certain viral infections, such as human papillomavirus (HPV). Histologically, BSCC is characterized by small, round basaloid cells with hyperchromatic nuclei. BSCC has an ulcerative infiltrative growth with comedonecrosis, intraluminal necrotic cells and/or karyorrhexis within cancer displaying cribriform or solid architecture, in the central lobules and peripheral nuclear palisading. Compared with classical SCC, BSCC seems to be more aggressive, as the majority of patients are diagnosed with late-stage disease and a high risk of frequent metastasis. The treatment options for SCC and BSCC are surgery, radiation or chemotherapy, depending on the grade and location of the tumor 5 . Most of the available data concerning this type of cancer have been derived from limited case reports and small-sample case series 7 . The incidence rate of BSCC reached 0.45 out of every 100,000 individuals in the United States of America from 2000–2013 6 . It is usually predominant among older white males between the sixth and seventh decades of life. Our objective was to provide an update on the clinicopathological characteristics and prognosis of BSCC in a large sample of patients from the Surveillance, Epidemiology, and End Results (SEER) database, a large population database. Our study was designed to compare patients diagnosed with BSCC of the nasopharynx, oropharynx, hypopharynx, oral cavity and tonsils with patients diagnosed with conventional SCC. 2. Methods 2.1. Data Source The Surveillance, Epidemiology, and End Results (SEER) program is a program of the National Cancer Institute (NCI), which is part of the National Institutes of Health (NIH) in the United States. The SEER program collects and publishes cancer incidence and survival data from various cancer registries across the country. Strategically located across the United States, the SEER registries routinely collect data on patient demographics, primary tumor site, tumor morphology, stage at diagnosis, first course of treatment, and follow-up vital status. Analyses from the SEER database are exempt from review by the institutional review board at Suez Canal University, given the deidentified data of the patients. 2.2. Patient Selection Patients diagnosed with SCC and BSCC of the head and neck between 2004 and 2020 were identified from the SEER database on the basis of the International Classification of Diseases for Oncology Histology and Site Codes 8 . Data were obtained via SEER Stat version 8.4.2 ( www.seerstat.gov/ ). The case listing generated in this study covered approximately 12.2% of the U.S. population and included data from 12 registries in several geographic regions. The inclusion criteria for this study were as follows: year of diagnosis between 2004 and 2020; primary sites in the oropharynx, nasopharynx, hypopharynx, oral cavity, and Waldeyer’s ring and tonsils; pathologically confirmed cases of ICD-O-3 codes 8070/3; squamous cell carcinoma, not otherwise specified [NOS]; 8071/3, squamous cell carcinoma, keratinizing; and 8083/3, basaloid squamous cell carcinoma. We excluded patients without a histologically confirmed diagnosis, those diagnosed at autopsy, those without a histologically confirmed diagnosis, those with nonkeratinizing SCC or other SCC variants (i.e., verrucous SCC, papillary SCC, spindle cell SCC) and those whose sites were coded as pharyngeal NOS, with overlapping lesions of the oral cavity and pharynx. 2.3 Variable Selection The extracted variables included sequence number, patient ID and demographic variables such as age at diagnosis, sex, and ethnicity. The extracted tumor factors included site, histological type, grade, and stage. The extracted treatment variable was surgery at the primary site because there was no cancer-directed surgery, radiation, surgery/radiation sequence or chemotherapy. Survival months and current vital status data were also extracted. Ethnicity was categorized as white, black, Asian/Pacific Islander, American Indian/Alaskan Native according to the SEER “race recoding” variable. Relying on the variables Primary Site – labeled, EOD Schema ID Recode (2010+) and site recoding ICD-O-3/WHO 2008, patients were classified into the following tumor location subgroups: oropharynx, nasopharynx, hypopharynx, oral cavity, and Waldeyer’s ring & tonsils. Waldeyer’s ring and tonsils were grouped together given their similar histopathological constitution of lymphoid tissue, their shared immunological function, and their location. We used the four-grade system for tumor grade classification, with four levels of differentiation from benign or borderline to undifferentiated, on the basis of the variable “pathological grade”, which included patients diagnosed after 2018; therefore, subgroup analysis was performed among patients diagnosed in or after this year. The treatment modalities used were surgery, radiation, surgery, radiation and chemotherapy. The study was reported according to the STORBE checklist for cross-sectional studies 9 . 2.4. Statistical analysis We compared the significant differences in clinicopathologic characteristics between BSCC patients and conventional SCC patients via the chi-square test for categorical variables and the Mann‒Whitney test for continuous variables that were not normally distributed. Kaplan–Meier survival analyses were used to compare overall survival (OS) between patients with BSCC and those with SCC. The log-rank test was used to assess significant differences between survival curves. Univariable analysis was performed to assess the effect of each variable on OS. A Cox proportional hazards regression model was developed to calculate the adjusted hazard ratios and control for confounders. A subgroup analysis was performed for the BSCC patients to compare survival at the five sites. All tests were two‐sided. A separate univariable and multivariable analysis of the BSCC cohort was performed, and significant variables were included in a nomogram with a significance threshold of 0.05. The model was evaluated via 10-fold cross-validation, and 100 bootstrap resamplings were used for calibration to decrease overfitting of the model. A nomogram was developed on the basis of the Cox proportional hazards model to predict OS in our cohort of patients. The analysis was conducted via SPSS version 26.0, Jamovi version 2.3.0, and R Studio version 4. 3. Results 3.1. Clinicopathological characteristics A total of 3,327 BSCC patients and 84,724 conventional-type SCC patients diagnosed between 2004 and 2020 were identified via the SEER database. Table 1 describes patient demographics and the distribution of tumor locations in each group. The median age of both groups was 61 years, with quartiles equal to 16 years above and below. Compared with SCC patients, a greater proportion of BSCC patients were white (85.8% vs. 89.9%, P < 0.001) and male (75.8% vs. 85.6%, P < 0.001). The oral cavity was the most frequent site (45.3% BSCC vs. 57% SCC, P < 0.001), followed by Waldeyer’s Ring & Tonsils (41.5% BSCC vs. 27.1% SCC, P < 0.001). Most BSCC patients presented with poor differentiation (3% vs. 2.4%, P < 0.001), whereas most SCC patients presented with moderate differentiation (5.6% vs. 0.5%, P < 0.001). To exclude blanks, a subgroup analysis was performed for the BSCC grade grouped by year between 2018 and 2020. The oral cavity, Waldeyer’s ring and tonsils were the least differentiated sites (41.6%), but the difference between the sites was not significant ( P value = 0.61). With respect to the null-grade values that the SEER database provides for patients diagnosed before 2018, 4.7% had high-grade BSCC, 0.3% had low-grade SCC, 95.3% had high-grade SCC, and 99.7% had low-grade SCC. Therefore, BSCC presented a higher grade than did SCC ( P value < 0.001). Both BSCC and SCC presented the most cases of stage III disease with regional metastasis (63.7%, P value < 0.001). Table 1 Compares patient demographics, primary tumor allocation, and clinical grades between the two groups. SCC (n = 84,724) BSCC (n = 3,327) All Respondents (n = 88,051) P- Value Age at diagnosis (per year) 0.032 Mean (SD) 60.87(.040) 60.36 (11.664) Median (IQ) 61 (16) 60 (16) Sex < 0.001 Female 20517 (24.2%) 480 (14.4%) 20997 Male 64207 (75.8%) 2847 (85.6%) 67054 Ethnicity < 0.001 White 72655 (85.8%) 2990 (89.9%) 75645 Black 6931 (8.2%) 230 (6.9%) 7161 Asian/Pacific Islander 4253 (5%) 69 (2.1%) 4322 American Indian/Alaska Native 495 (0.6%) 26 (0.8%) 521 Total 84334 (%99.5) 3327 (3.8%) 88051 Not recorded 390 (0.5%) 12 (0.4%) 402 Primary Site < 0.001 Oropharynx 4992 (5.9%) 177 (5.3%) 5169 Nasopharynx 2976 (3.5%) 84 (2.5%) 3060 Hypopharynx 5483 (6.5%) 176 (5.3%) 5659 Oral Cavity 48300 (57%) 1508 (45.3%) 49808 Waldeyer’s Ring & Tonsils 22973 (27.1%) 1382 (41.5%) 24355 Grade Well differentiated 1150 (1.4%) 0 1150 < 0.001 Moderately differentiated 4711 (5.6%) 16 (0.5%) 4727 Grade III Poorly differentiated 2029 (2.4%) 101 (3%) 2130 Undifferentiated 25 (0.02%) 1 (0.03%) 26 Total 7915 (9.3%) 118 (3.5%) 8033 Unknown 76809 (90.7%) 3209 (96.5%) 80018 3.2. Treatment Outcomes Treatment modality significantly differed between the two tumor groups ( Table 2 ) . A total of 41.2% of BSCC patients underwent surgical treatment, whereas 45.6% of SCC patients had P values < 0.001. A total of 52.1% of BSCC patients had radiation therapy, whereas 49.6% of SCC patients had a P value of 0.004. Adjunctive radiation and surgical treatment were more prevalent among BSCC patients (46.9% vs 42.4%, P value < 0.001). Similarly, chemotherapy was significantly more prevalent among BSCC patients (70.1% vs 59.7%, P value < 0.001). Table 2 Compares the pathological stages of the patients and the four treatment modalities available between the two groups. SCC (n = 84,724) BSCC (n = 3,327) All Respondents (n = 88,051) P Value Stage < 0.001 Stage 0 benign/borderline 2872 (3.4%) 68 (2%) 2940 Stage I in situ 0 0 0 Stage II Localized 14693 (17.3%) 337 (10.1%) 15030 Stage III Regional 53963 (63.7%) 2379 (63.7%) 56342 Stage IV distant 13196 (15.6%) 543 (15.6%) 13739 Surgery < 0.001 No 45968 (54.3%) 1948 (58.6%) 47916 Yes 38662 (45.6%) 1371 (41.2%) 40033 Unknown 94 (0.1%) 8 (0.2%) 102 Radiation 0.004 No 42704 (50.4%) 1592 (47.9%) 44296 Yes 42020 (49.6%) 1735 (52.1%) 43755 Surgery + Radiation < 0.001 No 42529 (50.2%) 1582 (47.6%) 44111 Yes 35959 (42.4%) 1559 (46.9%) 37518 Unknown 6236 (7.4%) 186 (5.6%) 6422 Chemotherapy < 0.001 No/Unknown 34161 (40.3%) 995 (29.9%) 35156 Yes 50563 (59.7%) 2332 (70.1%) 52895 3.3. Survival analysis The median follow-up duration for surviving patients was 40 months. Overall, the 3- and 5‐year survival rates were 0.86 and 0.81, respectively, among patients with BSCC and 0.75 and 0.71, respectively, among patients with SCC, with P < 0.001 ( Fig. 1 ) . The effect of tumor histology on OS for the five tumor sites is shown in Fig. 2 . Slight variations were presented when each site was analyzed separately (Figs. 3 – 7 ). The oropharynx (Fig. & 0.81 vs. 0.71 & 0.69) and nasopharynx (0.85 & 0.80 vs. 0.71 & 0.69) of the hypopharynx (0.86 & 0.81 vs. 0.71 & 0.69) of the BSCC and SCC. The oral cavity, Waldeyer’s ring and tonsils presented similar results. The univariable analysis of the overall cohort (Table 3 ) revealed that sex, ethnicity, site, grade, stage, radiation, radiation plus surgery and chemotherapy were significant factors affecting OS. All these variables remained significant in the multivariate analysis except for radiation and surgery. According to the multivariate analysis, BSCC patients were 39% less likely to die than SCC patients were (HR = 0.61, CI = 0.56–0.66, P < 0.001). Differences in the survival rates of patients with basaloid cell carcinoma with respect to different sites are shown in Appendix1 . Compared with BSCC in the oropharynx, the hypopharynx tumors presented the highest hazards and the lowest survival, with a greater than twofold increase in the hazard of death (HR = 2.35, CI = 0.63–3.41, P value < 0.001). Nasopharyngeal tumors increased the hazard of death by 0.02% (HR = 1.04, CI = 0.61–1.75, P value = 0.89). However, compared with the oropharynx cavity, the oral cavity reduced the hazard ratio by 28% (HR = 0.72, CI = 0.52–1.00, P value = 0.048), Waldeyer’s ring and tonsils by 51% (HR = 0.49, CI = 0.35–0.48, P value < 0.001). Table 3 Describes the univariable and multivariable analyses of the sample. Univariable Multivariable Hazard Ratio Confidence Interval P Value Hazard Ratio Confidence Interval P Value Age at diagnosis (per year) 1 (1–1) 0.427 1 (1–1) 0.372 Sex Female Reference Reference Male 0.79 (0.77–0.82) < 0.001 0.79 (0.77–0.81) < 0.001 Ethnicity White Reference Reference Black 1.80 (1.74–1.87) < 0.001 1.53 (1.47–1.59) < 0.001 Asian/Pacific Islander 1.08 (1.02–1.14) 0.013 0.99 (0.93–1.05) 0.767 American Indian/Alaska Native 1.04 (0.88–1.23) 0.648 0.93 (0.79–1.10) 0.376 Not recorde 0.22 (0.15–0.34) < 0.001 0.24 (0.16–0.36) < 0.001 Primary Site Oropharynx Reference Reference Nasopharynx 0.93 (0.86-1.00) 0.058 0.78 (0.72–0.84) < 0.001 Hypopharynx 1.66 (1.57–1.76) < 0.001 1.55 (1.46–1.64) < 0.001 Oral Cavity 0.78 (0.74–0.82) < 0.001 0.92 (0.88–0.97) 0.001 Waldeyer’s Ring & Tonsils 0.41 (0.39–0.43) < 0.001 0.49 (0.46–0.51) < 0.001 Grade Well differentiated Reference Reference Moderately differentiated 1.29 (1.03–1.62) 0.030 1.30 (1.03–1.63) 0.026 Poorly differentiated 1.58 (1.24–2.01) < 0.001 1.74 (1.36–2.22) < 0.001 Undifferentiated 1.12 (0.28–4.55) 0.873 1.31 (0.32–5.32) 0.705 Unknown 2.33 (1.89–2.87) < 0.001 1.88 (1.52–2.32) < 0.001 Stage Stage 0 benign/borderline Reference Reference Stage I in situ Stage II Localized 0.59 (0.55–0.63) < 0.001 0.66 (0.61–0.71) < 0.001 Stage III Regional 0.75 (0.70–0.80) < 0.001 1.04 (0.98–1.11) 0.219 Stage IV distant 1.63 (1.53–1.74) < 0.001 2.04 (1.90–2.18) < 0.001 Surgery No Reference Reference Yes 0.59 (0.58–0.61) < 0.001 0.70 (0.68–0.73) < 0.001 Unknown 1.17 (0.89–1.54) 0.260 0.80 (0.61–1.05) 0.111 Radiation No Reference Reference Yes 0.69 (0.67–0.70) < 0.001 0.74 (0.61–0.89) 0.001 Surgery + Radiation No Reference Reference Yes 0.59 (0.57–0.60) < 0.001 1.01 (0.84–1.22) 0.903 Unknown 1.28 (1.23–1.33) < 0.001 1.88 (1.56–2.25) < 0.001 Chemotherapy No Reference Reference Yes 0.92 (0.90–0.94) < 0.001 0.69 (0.67–0.71) < 0.001 Histological Type Squamous cell carcinoma Reference Reference Basaloid cell carcinoma 0.57 (0.53–0.61) < 0.001 0.61 (0.56–0.66) < 0.001 3.4. Nomogram A nomogram for OS was developed by incorporating all the independent variables identified in the multivariate analysis. Each variable was assigned a numerical score, and the cumulative score was calculated by summing these individual scores. Nomograms, which are graphical predictive tools, facilitate the determination of patients' probabilities of three- and five-year OS. To detect the discriminative capacity of the nomograms, we calculated the C-index value. The C-index value for these newly introduced models was 0.77 [95% confidence interval (CI): 0.6927346], indicating a high level of accuracy and reliability. The calibration curves exhibit a high level of reliability, demonstrating a strong alignment between the predictive values generated by the nomogram and the actual observations pertaining to 3- and 5-year OS. The nomogram was built on the basis of the significant variables in the univariable and multivariable Cox proportional hazards of the BSCC subgroup in Appendix 2 . The variable was considered be significant if p value less than 0.05. The model was evaluated via 10-fold cross-validation. One hundred bootstrap resamplings were used in the calibration to decrease overfitting of the model (Appendix 3, 4) . 4. Discussion Our study aimed to investigate the prognostic factors for OS in patients with BSCC in comparison to those with SCC at five head and neck tumor locations. We conducted a comparative analysis between BSCC and conventional SCC within the context of head and neck cancer. Our findings revealed that the three- and five-year OS rates for BSCC patients were 0.86 and 0.81, respectively, whereas those for conventional SCC patients were 0.75 and 0.71, respectively (Fig. 2 ). These results suggest a more favorable prognosis for BSCC patients, which is in line with the findings of Fritsch et al. However, compared with SCC patients, BSCC patients presented with higher tumor grades, which is in line with the findings of Moro-Sibilot et al. (2008)11. Our analysis was based on a cohort of 3,327 patients drawn from the SEER database, covering the period from 2004–2020. To the best of our knowledge, this study represents the most recent and largest investigation of BSCC across different head and neck sites. Recent studies conducted at various cancer centers and hospitals have delved into the attributes, surveillance methods, and prognostic factors related to BSCC across different head and neck sites. Ereño et al. conducted a study involving 40 patients with BSCC in the head and neck region and comprehensively analyzed the clinicopathological characteristics, follow-up outcomes, and prognoses of these patients. Their findings revealed a 3-year survival rate for half of the cases, with a notably reduced survival duration observed in patients presenting with positive lymph nodes 12 .. In another study, Thariat et al. investigated an additional 51 cases of BSCC within the head and neck and compared the OS outcomes between BSCC and conventional SCC. Their analysis revealed a significantly more favorable prognosis among BSCC patients than among those with conventional SCC [ 13 ]. A multivariate analysis to evaluate survival in their respective cohorts was not achievable because of limitations associated with the small sample sizes included in both studies. Similar site-specific SEER-based studies have also been conducted. Linton et al. investigated OS in 642 patients with BSCC of the oral cavity, oropharynx, larynx, or hypopharynx. Their analysis included only three-year survival rates, revealing that survival rates vary depending on the anatomical site within the head and neck region. While there was no significant difference in some sites (oral cavity, larynx, and hypopharynx), BSCC in the oropharynx was associated with a significantly lower risk of death than SCC [ 14 ]. Another study conducted by Shen et al. analyzed a cohort of 1163 patients diagnosed with primary BSCC in the lip, oral cavity, oropharynx, hypopharynx, or larynx. They reported that the five-year cumulative incidence of cause-specific mortality following the diagnosis of head and neck BSCC was 26.5%. Additionally, they reported that advanced age, larger tumor size, tumor location in the hypopharynx and larynx, lymph node involvement, distant metastasis, and the absence of radiotherapy treatment were positively associated with cause-specific mortality [ 15 ]. Another study by Fritsch et al. with a smaller sample size and former records investigated the same topic but focused more on the effect of the lesion site and underrepresented the different treatment modalities [ 5 ]. Another study compared BSCC and SCC but only in the oropharynx [ 10 ]. Their analysis revealed that the survival rates of BSCC vary depending on the anatomical site within the head and neck region. While there was no significant difference in some sites (oral cavity, larynx, and hypopharynx), BSCC in the oropharynx was associated with a significantly lower risk of death than SCC [ 14 ]. Another study conducted by Shen et al analyzed a cohort of 1163 patients diagnosed with primary BSCC in the lip, oral cavity, oropharynx, hypopharynx, and larynx. They reported that the five-year cumulative incidence of cause-specific mortality following the diagnosis of head and neck BSCC was 26.5%. Additionally, they reported that advanced age, larger tumor size, tumor location in the hypopharynx and larynx, lymph node involvement, distant metastasis, and the absence of radiotherapy treatment were positively associated with cause-specific mortality [ 15 ]. While BSCC is defined by the World Health Organization as an aggressive subtype of SCC 16 , our study suggests that when located in different head and neck sites, BSCCs exhibit more favorable clinical outcomes and survival than conventional SCCs found in the same anatomical region 17 . However, this aggressiveness may be attributed to the heightened mitotic activity of undifferentiated basaloid cells. Patients typically present at advanced stages, potentially indicative of the aggressive nature of these cases 18 . Our analysis revealed that a male predominance in BSCC occurred at various head and neck sites, with more than 80% of patients being males, with a mean age of 60 years. However, compared with females, males had a lower overall hazard of death in both samples. Both BSCC and conventional SCC are predominant representations of white ethnicity among their patient populations. Nevertheless, when considering patients of different ethnic backgrounds, those with SCC presented with a slightly greater prevalence of black and Asian/pacific Islander ethnicities than did those with BSCC. While both cancers had the highest prevalence in the “Oral Cavity”, followed by “Waldeyer’s Ring & Tonsils,” BSCC had a slightly lower incidence across other anatomical sites than did SCC. BSCC patients presented higher grades than did SCC patients, which coincides with previous studies [ 14 ]. The analysis of treatment modalities (surgery, radiation, surgery + radiation, and chemotherapy) revealed differences in the management of SCC and BSCC patients. SCC patients tend to receive surgery at higher rates than BSCC patients do, whereas BSCC patients have slightly higher rates of radiation therapy, combined surgery and radiation, and chemotherapy, suggesting that surgery is the first line of treatment for SCC and that radiation is the first line of BSCC treatment. After adjusting for other variables, our multivariate analysis revealed that age was not independently associated with OS in the whole cohort. Conversely, other variables, including sex, ethnicity, primary site, grade, stage, surgery, and radiation, demonstrated independent associations with survival, indicating their impact on survival outcomes. Compared with females, males had a 21% lower hazard; thus, they had greater survival rates than did their counterparts did, and those from nonwhite ethnic backgrounds experienced poorer survival outcomes. Notably, BSCC patients with primary tumors located in the oral cavity, Waldeyer’s ring and tonsils presented superior survival rates, whereas those with tumors in the hypopharynx presented the lowest OS compared with those with tumors in the nasopharynx. Moreover, patients who underwent surgical intervention, received radiation therapy or both presented increased survival rates. BSCC patients were more likely to receive multimodal therapy than SCC patients were. This suggests frequent indications of more aggressive treatment on the basis of the histological type and fear of serious complications, which are strongly enhanced by classical definitions of BSCC variants. Owing to high-risk features such as extracapsular spread and margin status, the SEER database does not provide [ 19 ]. Known for its aggressive nature and dismal prognosis, BSCC may react differently to treatment than SCC, especially in areas such as the larynx, hypopharynx, and oropharynx. Surgery is still the mainstay for localized disease and frequently provides the best chance of recovery, particularly when paired with adjuvant radiation or chemoradiotherapy in cases that have high-risk characteristics like extracapsular expansion or positive margins. However, studies indicate that BSCC may respond less well to radiation alone than SCC, possibly because of its different molecular profile. Chemoradiotherapy is commonly used for advanced or incurable cases. Chemotherapy, either as induction therapy or in combination with radiation, should also be investigated further because it may enhance locoregional control and survival in BSCC, which frequently manifests at an advanced stage. In order to improve therapy approaches for these histologically different yet clinically difficult cancers, the publication may help clarify how these treatment approaches affect survival differently in BSCC versus SCC across different anatomical subsites. Some potential limitations in our study should be acknowledged. First, our dataset lacks information on HPV status, a factor known to positively influence the prognosis of patients diagnosed with BSCC 20,21 .. Although HPV data have been available in the SEER database since 2004, they are frequently recorded as 'unknown' for a significant proportion of head and neck cancer patients. There is an association between BSCC and HPV, especially HPV-16, and HPV testing is considered an important test for determining the prognosis and possible treatment plans in BSCC patients [ 22 ]. According to Begum et al., in situ hybridization is better than PCR-based techniques for determining HPV16 status [ 23 ]. However, P16 expression is not always a reliable marker for HPV infection in oral BSCC patients. Moreover, the prevalence of HPV in BSCC depends mainly on the site, as oropharyngeal BSCC is more common than non-oropharyngeal BSCC. Moreover, compared with HPV-negative BSCC, HPV-positive BSCC has superior survival rates and a superior response to chemoradiotherapy, particularly in the oropharynx [ 23 , 24 ]. According to the WHO Blue Book, basaloid squamous cell carcinoma (BSCC) is a unique condition that is mainly found in the larynx and hypopharynx. It is distinguished by basaloid cells and a component of the stromal basement membrane. However, despite their different biological activity and prognosis, HPV-related non-keratinizing oropharyngeal cancers might be mistakenly categorized as BSCC, leading to diagnostic discrepancies. This emphasizes how crucial it is to differentiate between HPV-related oropharyngeal carcinomas and genuine, HPV-unrelated BSCC in order to do an appropriate survival analysis. Additionally, we did not explore the potential relationship between BSCC in the head or neck and the use of alcohol and tobacco for the same reason, both of which have been reported to be associated with BSCC [ 25 , 26 ]. We recommend further studies to investigate the disease-specific survival of each site separately. 5. Conclusion Our study comprises the most extensive cohort of patients diagnosed with BSCC in the head and neck. These findings indicate that patients with BSCC have a better prognosis concerning OS than do individuals diagnosed with conventional SCC, even though BSCC tends to be associated with higher tumor grades. Moreover, our analysis suggested that surgical intervention or radiation therapy may confer survival advantages to patients diagnosed with BSCC in the head and neck. Future research should cover each site separately. Abbreviations BSCC Basaloid squamous cell carcinoma SCC squamous cell carcinoma OS overall survival HPV human papillomavirus SEER Surveillance, Epidemiology, and End Results database NCI National Cancer Institute NIH National Institutes of Health ICD-O-3 International Classification of Diseases for Oncology, 3rd Edition NOS Not otherwise specified EOD Extent of disease STORBE Strengthening the reporting of observational studies in epidemiology Declarations Ethics approval and consent to participate Analyses from the SEER database are exempt from review by the institutional review board at Suez Canal University, given the deidentified data of the patients. Consent for publication Not applicable. Competing interests The authors have no relevant financial or non-financial interests to disclose. Funding No funding was received for conducting this study. Author Contribution Authors' contributionsRW: Conceptualization, manuscript writing, data curation.AE: Conceptualization, manuscript writing, data curation.MA: Conceptualization, manuscript writing, data curation.AA: Conceptualization, manuscript writing, data curation.AS: Manuscript writing, editing, and revision.All the authors have read and approved the final manuscript. Acknowledgments Not applicable. Availability of data and materials The datasets generated and/or analyzed during the current study are publicly available at https://seer.cancer.gov/ . References Thariat J, Badoual C, Faure C, Butori C, Marcy PY, Righini CA (2010) Basaloid squamous cell carcinoma of the head and neck: role of HPV and implication in treatment and prognosis. J Clin Pathol 63:857–866 Eren˜o C, Gaafar A, Garmendia M, Etxezarraga C, Bilbao FJ, Lo´pez JI (2008) Basaloid squamous cell carcinoma of the head and neck: a clinicopathological and follow-up study of 40 cases and review of the literature. Head Neck Pathol 2:83–91 Choussy O, Bertrand M, Francxois A, Blot E, Hamidou H, Dehesdin D (2011) Basaloid squamous cell carcinoma of the head and neck: report of 18 cases. J Laryngol Otol 125(6):608–613 Vasudev P, Boutross-Tadross O, Radhi J (2009) Basaloid squamous cell carcinoma: two case reports. Cases J 2:9351 Fritsch VA, Lentsch EJ (2014) Basaloid squamous cell carcinoma of the head and neck: location means everything. J Surg Oncol 109(6):616–622 Patel PN, Mutalik VS, Rehani S, Radhakrishnan R (2013) Basaloid squamous cell carcinoma of oral cavity with incongruent clinical course. BMJ case reports . ; 2013 Surveillance E, Results E (SEER) Program (eds) (2015) Surveillance, Epidemiology, and End Results (SEER) Program (www.seer.cancer.gov) SEER*Stat Database: Incidence - SEER 18 Regs Research Data + Hurricane Katrina Impacted Louisiana Cases, Nov 2015 Sub (1973–2013 varying) - Linked To County Attributes - Total U.S., 1969–2014 Counties, National Cancer Institute, DCCPS, Surveillance Research Program, Surveillance Systems Branch, released April 2016, based on the November submission World Health Organization (2013) International Classification of Diseases for Oncology, 3rd Edition (ICD-O-3) von Elm E, Altman DG, Egger M et al (2008) The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. J Clin Epidemiol 61(4):344–349 Fritsch VA, Lentsch EJ (2013) Basaloid squamous cell carcinoma of the oropharynx: an analysis of 650 cases. Otolaryngol Head Neck Surg 148(4):611–618 Moro-Sibilot D, Lantuejoul S, Diab S et al (2008) Lung carcinomas with a basaloid pattern: a study of 90 cases focusing on their poor prognosis. Eur Respir J 31(4):854–859 Ereño C, Gaafar A, Garmendia M, Etxezarraga C, Bilbao FJ, López JI (2008) Basaloid squamous cell carcinoma of the head and neck: a clinicopathological and follow-up study of 40 cases and review of the literature. Head Neck Pathol 2(2):83–91 Thariat J, Ahamad A, El-Naggar AK et al (2008) Outcomes after radiotherapy for basaloid squamous cell carcinoma of the head and neck: a case–control study. Cancer 112(12):2698–2709 Linton OR, Moore MG, Brigance JS, Gordon CA, Summerlin DJ, McDonald MW (2013) Prognostic significance of basaloid squamous cell carcinoma in head and neck cancer. JAMA Otolaryngol Head Neck Surg 139(12):1306–1311 Shen W, Sakamoto N, Yang L (2018) Cause-specific mortality prediction model for patients with basaloid squamous cell carcinomas of the head and neck: a competing risk analysis. J Cancer 9(21):4009–4017 EI-Naggar AK, Chan JK, C. G, randis JR, Takata T, Slootweg PJ (eds) (2017) Thompson L (2006) World Health Organization classification of tumors: pathology and genetics of head and neck tumors. Ear Nose Throat J 85(2):74 Jain N, Raut T, Keshwar S, Shrestha A, Jaisani MR, Paudel D (2023) Histopathological Characterization of a Series of Oral Basaloid Squamous Cell Carcinoma. Case Rep Dent 2023:6036567 Barnes C, Eveson J, Reichart P et al (2005) Pathology and Genetics: Head and Neck Tumors: World Health Organization Classification of Tumors. IARC, Lyon, France Begum S, Westra WH (2008) Basaloid squamous cell carcinoma of the head and neck is a mixed variant that can be further resolved by HPV status. Am J Surg Pathol 32(7):1044–1050 Chernock RD, Lewis JS, Zhang Q, El-Mofty SK (2010) Human papillomavirus-positive basaloid squamous cell carcinomas of the upper aerodigestive tract: a distinct clinicopathologic and molecular subtype of basaloid squamous cell carcinoma. Hum Pathol 41(7):1016–1023 Friedrich RE, Sperber C, Jäkel T, Röser K, Löning T (2010) Basaloid lesions of oral squamous epithelial cells and their association with HPV infection and P16 expression. Anticancer Res 30(5):1605–1612 Begum S, Westra WH (2008) Basaloid squamous cell carcinoma of the head and neck is a mixed variant that can be further resolved by HPV status. Am J Surg Pathol 32(7):1044–1050 Jacobi C, Ayx I, Fritsche K, Piontek G, Hoffmann D, Weirich G, Knopf A (2015) Potential impact of human papilloma virus on survival of basaloid squamous carcinoma of the head and neck. Oncotarget 6:3462–3470 Vasudev P, Boutross-Tadross O, Radhi J (2009) Basaloid squamous cell carcinoma: two case reports. Cases J 2:9351 Woolgar JA, Lewis JS Jr, Devaney KO et al (2011) Basaloid squamous cell carcinoma of the upper aerodigestive tract: a single squamous cell carcinoma subtype or two distinct entities hiding under one histologic pattern? Eur Arch Otorhinolaryngol 268(2):161–164 Additional Declarations No competing interests reported. Supplementary Files Appendixes.pdf Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6189154","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":427204092,"identity":"6771c2f8-8d1c-4334-ad80-c0fd400c442c","order_by":0,"name":"Rim Wally","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABKUlEQVRIie3RsUrEMBjA8YRCukTPsVBtXiFSEI6D81VaCr0loqOgYEDILYprfQtBOBwLxeuSwTGjInQSrrcIwnmY2EUwBd0E8x+SQvmRLy0ALtcfbJ93+/Ym8Mrgywuvl9Cy2zECKNGE/opg+kNSn9/fQDHGKGBLtbxbAVJkVQuORyn3pw/Wu1zMcwVFpsnB7fBaUkBVnlAgJynH8shGxgHbU3DmGTILN4QmAaMJFFXKA5bYSEwWr5qcmcGa8F0TUhy2JVxrQl6sZLfASJPKEBRCTYBikENuTvFL6/Vlrgdb1xjhJh5eihhT2cQgmU9igVnPF6saBeRJNPCzJ/UmoohMs+e2PR3tXPn1o9XovJVZt7rB8edqns2f6iNdg++D+72nuFwu17/qA3qfX8qOnnDoAAAAAElFTkSuQmCC","orcid":"","institution":"Suez Canal University","correspondingAuthor":true,"prefix":"","firstName":"Rim","middleName":"","lastName":"Wally","suffix":""},{"id":427204093,"identity":"d07a3d55-8144-470d-a716-ffd5e73563ec","order_by":1,"name":"Ahmed Elkoumi","email":"","orcid":"","institution":"Egyptian Russian University","correspondingAuthor":false,"prefix":"","firstName":"Ahmed","middleName":"","lastName":"Elkoumi","suffix":""},{"id":427204097,"identity":"fbe04755-121d-4bce-9a49-0cec42d08f6a","order_by":2,"name":"Maged Ahmed Mohamed","email":"","orcid":"","institution":"Alazhar University","correspondingAuthor":false,"prefix":"","firstName":"Maged","middleName":"Ahmed","lastName":"Mohamed","suffix":""},{"id":427204099,"identity":"6a387e7e-08a5-45ce-98b2-a5e9bc870db0","order_by":3,"name":"Moamen Mostafa Asla","email":"","orcid":"","institution":"Zagazig University","correspondingAuthor":false,"prefix":"","firstName":"Moamen","middleName":"Mostafa","lastName":"Asla","suffix":""},{"id":427204100,"identity":"113c27d1-ca10-4fc0-9b54-783b7f23dbee","order_by":4,"name":"Abdelaziz A. Awad","email":"","orcid":"","institution":"Alazhar University","correspondingAuthor":false,"prefix":"","firstName":"Abdelaziz","middleName":"A.","lastName":"Awad","suffix":""},{"id":427204101,"identity":"a36d1bcf-5afd-4afb-983d-cf5ba1dd7cd2","order_by":5,"name":"Abeer Shaalan","email":"","orcid":"","institution":"King’s College London, Guy’s Hospital","correspondingAuthor":false,"prefix":"","firstName":"Abeer","middleName":"","lastName":"Shaalan","suffix":""}],"badges":[],"createdAt":"2025-03-09 14:23:08","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6189154/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6189154/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":78643931,"identity":"8a145d1a-28cd-4858-a052-f80dad59448f","added_by":"auto","created_at":"2025-03-17 07:15:18","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":25390,"visible":true,"origin":"","legend":"\u003cp\u003ecompares the overall three- and five-year survival rates of all sites combined between the two groups.\u003c/p\u003e","description":"","filename":"image1.png","url":"https://assets-eu.researchsquare.com/files/rs-6189154/v1/56c192209a6334ddda00d624.png"},{"id":78642845,"identity":"033070f5-f9f7-4026-b358-ff0cc88e58b7","added_by":"auto","created_at":"2025-03-17 07:07:18","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":51763,"visible":true,"origin":"","legend":"\u003cp\u003eshows the effect of tumor histopathological type on overall survival.\u003c/p\u003e","description":"","filename":"image2.png","url":"https://assets-eu.researchsquare.com/files/rs-6189154/v1/89fceaadc87f9f91f1b5b505.png"},{"id":78643932,"identity":"a5b5ad1e-59c6-4ddb-a11a-78132f249e52","added_by":"auto","created_at":"2025-03-17 07:15:18","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":27724,"visible":true,"origin":"","legend":"\u003cp\u003ecompares the three- and five-year survival rates in the oropharynx between the two groups.\u003c/p\u003e","description":"","filename":"image3.png","url":"https://assets-eu.researchsquare.com/files/rs-6189154/v1/26f4617e6d98f879e354e83c.png"},{"id":78642846,"identity":"d7e55fcd-617f-4982-bf36-92c9bbc3888d","added_by":"auto","created_at":"2025-03-17 07:07:18","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":25109,"visible":true,"origin":"","legend":"\u003cp\u003ecompares the three- and five-year survival rates in the nasopharynx between the two groups.\u003c/p\u003e","description":"","filename":"image4.png","url":"https://assets-eu.researchsquare.com/files/rs-6189154/v1/68e023c535cc24a33a67e4e6.png"},{"id":78643933,"identity":"92a82b01-026b-4638-9c83-7a1d91c98682","added_by":"auto","created_at":"2025-03-17 07:15:18","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":25025,"visible":true,"origin":"","legend":"\u003cp\u003ecomparison of three- and five-year survival in the hypopharynx between the two groups\u003c/p\u003e","description":"","filename":"image5.png","url":"https://assets-eu.researchsquare.com/files/rs-6189154/v1/3edc0077403aefb322493f6f.png"},{"id":78642851,"identity":"44a12d60-1065-4f54-a9e2-cb1659141b13","added_by":"auto","created_at":"2025-03-17 07:07:18","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":24805,"visible":true,"origin":"","legend":"\u003cp\u003ecompares the three- and five-year survival rates in the oral cavity between the two groups.\u003c/p\u003e","description":"","filename":"image6.png","url":"https://assets-eu.researchsquare.com/files/rs-6189154/v1/e770ece85d530ea7e17bc30c.png"},{"id":78642854,"identity":"70752abc-f164-48b0-a74a-a907b4b91471","added_by":"auto","created_at":"2025-03-17 07:07:19","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":28354,"visible":true,"origin":"","legend":"\u003cp\u003ecompares the three- and five-year survival rates between the two groups in Waldeyer’s ring and tonsils.\u003c/p\u003e","description":"","filename":"image7.png","url":"https://assets-eu.researchsquare.com/files/rs-6189154/v1/923cdd7fcc52eb48549563cf.png"},{"id":78644267,"identity":"accc7c26-4958-4d8a-ba40-95ec35999e14","added_by":"auto","created_at":"2025-03-17 07:23:23","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1218709,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6189154/v1/aa1eb44a-c7b3-4e07-a7fe-a8fe8d386ce8.pdf"},{"id":78642852,"identity":"7987e756-e44a-42ac-930b-a75d1345267f","added_by":"auto","created_at":"2025-03-17 07:07:18","extension":"pdf","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":560712,"visible":true,"origin":"","legend":"","description":"","filename":"Appendixes.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6189154/v1/3a4727f5fabf5581e69e2dca.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Survival Outcomes of BSCC Variant Compared with SCC of the Head and Neck: A Cross-Sectional SEER-Based Analysis","fulltext":[{"header":"1. Background","content":"\u003cp\u003eBasaloid squamous cell carcinoma (BSCC) is a rare and aggressive histopathological variant of squamous cell carcinoma (SCC). BSCCs are characterized by both basal cell carcinoma and squamous cell carcinoma with poor prognoses and high rates of distant metastases. BSCC can occur at various anatomical sites. BSCC is most commonly associated with the upper aerodigestive tract, but it can also occur in other locations, such as the skin, anogenital region and lungs. In the head and neck region, BSCC occurs in the larynx, hypopharynx, and base of the tongue \u0026sup1;-\u0026sup3;. Like other types of squamous cell carcinoma, risk factors for BSCC may include exposure to ultraviolet radiation, tobacco use, alcohol consumption, and certain viral infections, such as human papillomavirus (HPV).\u003c/p\u003e \u003cp\u003eHistologically, BSCC is characterized by small, round basaloid cells with hyperchromatic nuclei. BSCC has an ulcerative infiltrative growth with comedonecrosis, intraluminal necrotic cells and/or karyorrhexis within cancer displaying cribriform or solid architecture, in the central lobules and peripheral nuclear palisading. Compared with classical SCC, BSCC seems to be more aggressive, as the majority of patients are diagnosed with late-stage disease and a high risk of frequent metastasis. The treatment options for SCC and BSCC are surgery, radiation or chemotherapy, depending on the grade and location of the tumor \u003csup\u003e5\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eMost of the available data concerning this type of cancer have been derived from limited case reports and small-sample case series \u003csup\u003e7\u003c/sup\u003e. The incidence rate of BSCC reached 0.45 out of every 100,000 individuals in the United States of America from 2000\u0026ndash;2013 \u003csup\u003e6\u003c/sup\u003e. It is usually predominant among older white males between the sixth and seventh decades of life.\u003c/p\u003e \u003cp\u003eOur objective was to provide an update on the clinicopathological characteristics and prognosis of BSCC in a large sample of patients from the Surveillance, Epidemiology, and End Results (SEER) database, a large population database. Our study was designed to compare patients diagnosed with BSCC of the nasopharynx, oropharynx, hypopharynx, oral cavity and tonsils with patients diagnosed with conventional SCC.\u003c/p\u003e"},{"header":"2. Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1. Data Source\u003c/h2\u003e \u003cp\u003eThe Surveillance, Epidemiology, and End Results (SEER) program is a program of the National Cancer Institute (NCI), which is part of the National Institutes of Health (NIH) in the United States. The SEER program collects and publishes cancer incidence and survival data from various cancer registries across the country. Strategically located across the United States, the SEER registries routinely collect data on patient demographics, primary tumor site, tumor morphology, stage at diagnosis, first course of treatment, and follow-up vital status. Analyses from the SEER database are exempt from review by the institutional review board at Suez Canal University, given the deidentified data of the patients.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2. \u003cem\u003ePatient Selection\u003c/em\u003e\u003c/h2\u003e \u003cp\u003ePatients diagnosed with SCC and BSCC of the head and neck between 2004 and 2020 were identified from the SEER database on the basis of the International Classification of Diseases for Oncology Histology and Site Codes \u003csup\u003e8\u003c/sup\u003e. Data were obtained via SEER Stat version 8.4.2 (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ewww.seerstat.gov/\u003c/a\u003e\u003c/span\u003e\u003cspan address=\"http://www.seerstat.gov/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e).\u003c/span\u003e The case listing generated in this study covered approximately 12.2% of the U.S. population and included data from 12 registries in several geographic regions. The inclusion criteria for this study were as follows: year of diagnosis between 2004 and 2020; primary sites in the oropharynx, nasopharynx, hypopharynx, oral cavity, and Waldeyer\u0026rsquo;s ring and tonsils; pathologically confirmed cases of ICD-O-3 codes 8070/3; squamous cell carcinoma, not otherwise specified [NOS]; 8071/3, squamous cell carcinoma, keratinizing; and 8083/3, basaloid squamous cell carcinoma. We excluded patients without a histologically confirmed diagnosis, those diagnosed at autopsy, those without a histologically confirmed diagnosis, those with nonkeratinizing SCC or other SCC variants (i.e., verrucous SCC, papillary SCC, spindle cell SCC) and those whose sites were coded as pharyngeal NOS, with overlapping lesions of the oral cavity and pharynx.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3 Variable Selection\u003c/h2\u003e \u003cp\u003eThe extracted variables included sequence number, patient ID and demographic variables such as age at diagnosis, sex, and ethnicity. The extracted tumor factors included site, histological type, grade, and stage. The extracted treatment variable was surgery at the primary site because there was no cancer-directed surgery, radiation, surgery/radiation sequence or chemotherapy. Survival months and current vital status data were also extracted. Ethnicity was categorized as white, black, Asian/Pacific Islander, American Indian/Alaskan Native according to the SEER \u0026ldquo;race recoding\u0026rdquo; variable. Relying on the variables Primary Site \u0026ndash; labeled, EOD Schema ID Recode (2010+) and site recoding ICD-O-3/WHO 2008, patients were classified into the following tumor location subgroups: oropharynx, nasopharynx, hypopharynx, oral cavity, and Waldeyer\u0026rsquo;s ring \u0026amp; tonsils. Waldeyer\u0026rsquo;s ring and tonsils were grouped together given their similar histopathological constitution of lymphoid tissue, their shared immunological function, and their location.\u003c/p\u003e \u003cp\u003eWe used the four-grade system for tumor grade classification, with four levels of differentiation from benign or borderline to undifferentiated, on the basis of the variable \u0026ldquo;pathological grade\u0026rdquo;, which included patients diagnosed after 2018; therefore, subgroup analysis was performed among patients diagnosed in or after this year. The treatment modalities used were surgery, radiation, surgery, radiation and chemotherapy. The study was reported according to the STORBE checklist for cross-sectional studies\u003csup\u003e9\u003c/sup\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4. Statistical analysis\u003c/h2\u003e \u003cp\u003eWe compared the significant differences in clinicopathologic characteristics between BSCC patients and conventional SCC patients via the chi-square test for categorical variables and the Mann‒Whitney test for continuous variables that were not normally distributed. Kaplan\u0026ndash;Meier survival analyses were used to compare overall survival (OS) between patients with BSCC and those with SCC. The log-rank test was used to assess significant differences between survival curves. Univariable analysis was performed to assess the effect of each variable on OS. A Cox proportional hazards regression model was developed to calculate the adjusted hazard ratios and control for confounders. A subgroup analysis was performed for the BSCC patients to compare survival at the five sites. All tests were two‐sided. A separate univariable and multivariable analysis of the BSCC cohort was performed, and significant variables were included in a nomogram with a significance threshold of 0.05. The model was evaluated via 10-fold cross-validation, and 100 bootstrap resamplings were used for calibration to decrease overfitting of the model. A nomogram was developed on the basis of the Cox proportional hazards model to predict OS in our cohort of patients. The analysis was conducted via SPSS version 26.0, Jamovi version 2.3.0, and R Studio version 4.\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e3.1. Clinicopathological characteristics\u003c/h2\u003e \u003cp\u003eA total of 3,327 BSCC patients and 84,724 conventional-type SCC patients diagnosed between 2004 and 2020 were identified via the SEER database. Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e describes patient demographics and the distribution of tumor locations in each group. The median age of both groups was 61 years, with quartiles equal to 16 years above and below. Compared with SCC patients, a greater proportion of BSCC patients were white (85.8% vs. 89.9%, \u003cb\u003eP\u003c/b\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and male (75.8% vs. 85.6%, \u003cb\u003eP\u003c/b\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003eThe oral cavity was the most frequent site (45.3% BSCC vs. 57% SCC, \u003cb\u003eP\u003c/b\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), followed by Waldeyer\u0026rsquo;s Ring \u0026amp; Tonsils (41.5% BSCC vs. 27.1% SCC, \u003cb\u003eP\u003c/b\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Most BSCC patients presented with poor differentiation (3% vs. 2.4%, \u003cb\u003eP\u003c/b\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), whereas most SCC patients presented with moderate differentiation (5.6% vs. 0.5%, \u003cb\u003eP\u003c/b\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). To exclude blanks, a subgroup analysis was performed for the BSCC grade grouped by year between 2018 and 2020. The oral cavity, Waldeyer\u0026rsquo;s ring and tonsils were the least differentiated sites (41.6%), but the difference between the sites was not significant (\u003cb\u003eP\u003c/b\u003e value\u0026thinsp;=\u0026thinsp;0.61). With respect to the null-grade values that the SEER database provides for patients diagnosed before 2018, 4.7% had high-grade BSCC, 0.3% had low-grade SCC, 95.3% had high-grade SCC, and 99.7% had low-grade SCC. Therefore, BSCC presented a higher grade than did SCC (\u003cb\u003eP\u003c/b\u003e value\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Both BSCC and SCC presented the most cases of stage III disease with regional metastasis (63.7%, \u003cb\u003eP\u003c/b\u003e value\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCompares patient demographics, primary tumor allocation, and clinical grades between the two groups.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSCC\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;84,724)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBSCC\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;3,327)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAll Respondents\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;88,051)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP- Value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge at diagnosis (per year)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.032\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean (SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e60.87(.040)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e60.36 (11.664)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian (IQ)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e61 (16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e60 (16)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSex\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20517 (24.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e480 (14.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20997\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e64207 (75.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2847 (85.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e67054\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eEthnicity\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"6\" rowspan=\"7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWhite\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e72655 (85.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2990 (89.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e75645\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBlack\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6931 (8.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e230 (6.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7161\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAsian/Pacific Islander\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4253 (5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e69 (2.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4322\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAmerican Indian/Alaska Native\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e495 (0.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26 (0.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e521\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e84334 (%99.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3327 (3.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e88051\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNot recorded\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e390 (0.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 (0.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e402\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePrimary Site\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"5\" rowspan=\"6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOropharynx\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4992 (5.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e177 (5.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5169\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNasopharynx\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2976 (3.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e84 (2.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3060\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypopharynx\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5483 (6.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e176 (5.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5659\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOral Cavity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e48300 (57%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1508 (45.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e49808\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWaldeyer\u0026rsquo;s Ring \u0026amp; Tonsils\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22973 (27.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1382 (41.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e24355\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGrade\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWell differentiated\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1150 (1.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1150\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"5\" rowspan=\"6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eModerately differentiated\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4711 (5.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (0.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4727\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGrade III Poorly differentiated\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2029 (2.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e101 (3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2130\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUndifferentiated\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25 (0.02%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (0.03%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e26\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7915 (9.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e118 (3.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8033\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e76809 (90.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3209 (96.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e80018\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e3.2. Treatment Outcomes\u003c/h2\u003e \u003cp\u003eTreatment modality significantly differed between the two tumor groups \u003cb\u003e(\u003c/b\u003eTable\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e. A total of 41.2% of BSCC patients underwent surgical treatment, whereas 45.6% of SCC patients had P values\u0026thinsp;\u0026lt;\u0026thinsp;0.001. A total of 52.1% of BSCC patients had radiation therapy, whereas 49.6% of SCC patients had a P value of 0.004. Adjunctive radiation and surgical treatment were more prevalent among BSCC patients (46.9% vs 42.4%, \u003cb\u003eP\u003c/b\u003e value\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Similarly, chemotherapy was significantly more prevalent among BSCC patients (70.1% vs 59.7%, \u003cb\u003eP\u003c/b\u003e value\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCompares the pathological stages of the patients and the four treatment modalities available between the two groups.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSCC\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;84,724)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003eBSCC\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;3,327)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003eAll Respondents\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;88,051)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eP Value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eStage\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\" morerows=\"5\" rowspan=\"6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStage 0 benign/borderline\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2872 (3.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e68 (2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e2940\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStage I in situ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStage II Localized\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14693 (17.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e337 (10.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e15030\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStage III Regional\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e53963 (63.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e2379 (63.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e56342\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStage IV distant\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13196 (15.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e543 (15.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e13739\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSurgery\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e45968 (54.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e1948 (58.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e47916\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e38662 (45.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e1371 (41.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e40033\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e94 (0.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e8 (0.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e102\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRadiation\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.004\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e42704 (50.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e1592 (47.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e44296\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e42020 (49.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e1735 (52.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e43755\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSurgery\u0026thinsp;+\u0026thinsp;Radiation\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e42529 (50.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e1582 (47.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e44111\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e35959 (42.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e1559 (46.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e37518\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6236 (7.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e186 (5.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e6422\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eChemotherapy\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo/Unknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e34161 (40.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e995 (29.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e35156\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50563 (59.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e2332 (70.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e52895\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003e3.3. Survival analysis\u003c/h2\u003e \u003cp\u003eThe median follow-up duration for surviving patients was 40 months. Overall, the 3- and 5‐year survival rates were 0.86 and 0.81, respectively, among patients with BSCC and 0.75 and 0.71, respectively, among patients with SCC, with \u003cb\u003eP\u003c/b\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001 \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e. The effect of tumor histology on OS for the five tumor sites is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Slight variations were presented when each site was analyzed separately (Figs.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e7\u003c/span\u003e). The oropharynx (Fig. \u0026amp; 0.81 vs. 0.71 \u0026amp; 0.69) and nasopharynx (0.85 \u0026amp; 0.80 vs. 0.71 \u0026amp; 0.69) of the hypopharynx (0.86 \u0026amp; 0.81 vs. 0.71 \u0026amp; 0.69) of the BSCC and SCC. The oral cavity, Waldeyer\u0026rsquo;s ring and tonsils presented similar results.\u003c/p\u003e \u003cp\u003eThe univariable analysis of the overall cohort (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e) revealed that sex, ethnicity, site, grade, stage, radiation, radiation plus surgery and chemotherapy were significant factors affecting OS. All these variables remained significant in the multivariate analysis except for radiation and surgery. According to the multivariate analysis, BSCC patients were 39% less likely to die than SCC patients were (HR\u0026thinsp;=\u0026thinsp;0.61, CI\u0026thinsp;=\u0026thinsp;0.56\u0026ndash;0.66, \u003cb\u003eP\u003c/b\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Differences in the survival rates of patients with basaloid cell carcinoma with respect to different sites are shown in \u003cb\u003eAppendix1\u003c/b\u003e. Compared with BSCC in the oropharynx, the hypopharynx tumors presented the highest hazards and the lowest survival, with a greater than twofold increase in the hazard of death (HR\u0026thinsp;=\u0026thinsp;2.35, CI\u0026thinsp;=\u0026thinsp;0.63\u0026ndash;3.41, \u003cb\u003eP\u003c/b\u003e value\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Nasopharyngeal tumors increased the hazard of death by 0.02% (HR\u0026thinsp;=\u0026thinsp;1.04, CI\u0026thinsp;=\u0026thinsp;0.61\u0026ndash;1.75, P value\u0026thinsp;=\u0026thinsp;0.89). However, compared with the oropharynx cavity, the oral cavity reduced the hazard ratio by 28% (HR\u0026thinsp;=\u0026thinsp;0.72, CI\u0026thinsp;=\u0026thinsp;0.52\u0026ndash;1.00, P value\u0026thinsp;=\u0026thinsp;0.048), Waldeyer\u0026rsquo;s ring and tonsils by 51% (HR\u0026thinsp;=\u0026thinsp;0.49, CI\u0026thinsp;=\u0026thinsp;0.35\u0026ndash;0.48, P value\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDescribes the univariable and multivariable analyses of the sample.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eUnivariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e \u003cp\u003eMultivariable\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHazard Ratio\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eConfidence Interval\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP Value\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHazard Ratio\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eConfidence Interval\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eP Value\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge at diagnosis (per year)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(1\u0026ndash;1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.427\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e(1\u0026ndash;1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.372\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSex\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(0.77\u0026ndash;0.82)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e(0.77\u0026ndash;0.81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eEthnicity\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWhite\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBlack\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(1.74\u0026ndash;1.87)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e(1.47\u0026ndash;1.59)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAsian/Pacific Islander\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(1.02\u0026ndash;1.14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.013\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e(0.93\u0026ndash;1.05)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.767\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAmerican Indian/Alaska Native\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(0.88\u0026ndash;1.23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.648\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e(0.79\u0026ndash;1.10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.376\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNot recorde\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(0.15\u0026ndash;0.34)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e(0.16\u0026ndash;0.36)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePrimary Site\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOropharynx\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNasopharynx\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(0.86-1.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.058\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e(0.72\u0026ndash;0.84)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypopharynx\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(1.57\u0026ndash;1.76)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e(1.46\u0026ndash;1.64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOral Cavity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(0.74\u0026ndash;0.82)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e(0.88\u0026ndash;0.97)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWaldeyer\u0026rsquo;s Ring \u0026amp; Tonsils\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(0.39\u0026ndash;0.43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e(0.46\u0026ndash;0.51)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGrade\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWell differentiated\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eModerately differentiated\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(1.03\u0026ndash;1.62)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.030\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e(1.03\u0026ndash;1.63)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.026\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePoorly differentiated\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(1.24\u0026ndash;2.01)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.74\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e(1.36\u0026ndash;2.22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUndifferentiated\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(0.28\u0026ndash;4.55)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.873\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e(0.32\u0026ndash;5.32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.705\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(1.89\u0026ndash;2.87)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e(1.52\u0026ndash;2.32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eStage\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStage 0 benign/borderline\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStage I in situ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStage II Localized\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(0.55\u0026ndash;0.63)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e(0.61\u0026ndash;0.71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStage III Regional\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(0.70\u0026ndash;0.80)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e(0.98\u0026ndash;1.11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.219\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStage IV distant\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(1.53\u0026ndash;1.74)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e(1.90\u0026ndash;2.18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSurgery\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(0.58\u0026ndash;0.61)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e(0.68\u0026ndash;0.73)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(0.89\u0026ndash;1.54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.260\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e(0.61\u0026ndash;1.05)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.111\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRadiation\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(0.67\u0026ndash;0.70)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.74\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e(0.61\u0026ndash;0.89)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSurgery\u0026thinsp;+\u0026thinsp;Radiation\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(0.57\u0026ndash;0.60)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e(0.84\u0026ndash;1.22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.903\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(1.23\u0026ndash;1.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e(1.56\u0026ndash;2.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eChemotherapy\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(0.90\u0026ndash;0.94)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e(0.67\u0026ndash;0.71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHistological Type\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSquamous cell\u003c/p\u003e \u003cp\u003ecarcinoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBasaloid cell carcinoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(0.53\u0026ndash;0.61)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e(0.56\u0026ndash;0.66)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003e3.4. Nomogram\u003c/h2\u003e \u003cp\u003eA nomogram for OS was developed by incorporating all the independent variables identified in the multivariate analysis. Each variable was assigned a numerical score, and the cumulative score was calculated by summing these individual scores. Nomograms, which are graphical predictive tools, facilitate the determination of patients' probabilities of three- and five-year OS. To detect the discriminative capacity of the nomograms, we calculated the C-index value. The C-index value for these newly introduced models was 0.77 [95% confidence interval (CI): 0.6927346], indicating a high level of accuracy and reliability. The calibration curves exhibit a high level of reliability, demonstrating a strong alignment between the predictive values generated by the nomogram and the actual observations pertaining to 3- and 5-year OS. The nomogram was built on the basis of the significant variables in the univariable and multivariable Cox proportional hazards of the BSCC subgroup in \u003cb\u003eAppendix 2\u003c/b\u003e. The variable was considered be significant if \u003cb\u003ep\u003c/b\u003e value less than 0.05. The model was evaluated via 10-fold cross-validation. One hundred bootstrap resamplings were used in the calibration to decrease overfitting of the model \u003cb\u003e(Appendix 3, 4)\u003c/b\u003e.\u003c/p\u003e \u003c/div\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eOur study aimed to investigate the prognostic factors for OS in patients with BSCC in comparison to those with SCC at five head and neck tumor locations. We conducted a comparative analysis between BSCC and conventional SCC within the context of head and neck cancer. Our findings revealed that the three- and five-year OS rates for BSCC patients were 0.86 and 0.81, respectively, whereas those for conventional SCC patients were 0.75 and 0.71, respectively (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). These results suggest a more favorable prognosis for BSCC patients, which is in line with the findings of Fritsch et al. However, compared with SCC patients, BSCC patients presented with higher tumor grades, which is in line with the findings of Moro-Sibilot et al. (2008)11. Our analysis was based on a cohort of 3,327 patients drawn from the SEER database, covering the period from 2004\u0026ndash;2020. To the best of our knowledge, this study represents the most recent and largest investigation of BSCC across different head and neck sites.\u003c/p\u003e \u003cp\u003eRecent studies conducted at various cancer centers and hospitals have delved into the attributes, surveillance methods, and prognostic factors related to BSCC across different head and neck sites. Ere\u0026ntilde;o et al. conducted a study involving 40 patients with BSCC in the head and neck region and comprehensively analyzed the clinicopathological characteristics, follow-up outcomes, and prognoses of these patients. Their findings revealed a 3-year survival rate for half of the cases, with a notably reduced survival duration observed in patients presenting with positive lymph nodes \u003csup\u003e12\u003c/sup\u003e.. In another study, Thariat et al. investigated an additional 51 cases of BSCC within the head and neck and compared the OS outcomes between BSCC and conventional SCC. Their analysis revealed a significantly more favorable prognosis among BSCC patients than among those with conventional SCC [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. A multivariate analysis to evaluate survival in their respective cohorts was not achievable because of limitations associated with the small sample sizes included in both studies.\u003c/p\u003e \u003cp\u003eSimilar site-specific SEER-based studies have also been conducted. Linton et al. investigated OS in 642 patients with BSCC of the oral cavity, oropharynx, larynx, or hypopharynx. Their analysis included only three-year survival rates, revealing that survival rates vary depending on the anatomical site within the head and neck region. While there was no significant difference in some sites (oral cavity, larynx, and hypopharynx), BSCC in the oropharynx was associated with a significantly lower risk of death than SCC [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Another study conducted by Shen et al. analyzed a cohort of 1163 patients diagnosed with primary BSCC in the lip, oral cavity, oropharynx, hypopharynx, or larynx. They reported that the five-year cumulative incidence of cause-specific mortality following the diagnosis of head and neck BSCC was 26.5%. Additionally, they reported that advanced age, larger tumor size, tumor location in the hypopharynx and larynx, lymph node involvement, distant metastasis, and the absence of radiotherapy treatment were positively associated with cause-specific mortality [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Another study by Fritsch et al. with a smaller sample size and former records investigated the same topic but focused more on the effect of the lesion site and underrepresented the different treatment modalities [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Another study compared BSCC and SCC but only in the oropharynx [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eTheir analysis revealed that the survival rates of BSCC vary depending on the anatomical site within the head and neck region. While there was no significant difference in some sites (oral cavity, larynx, and hypopharynx), BSCC in the oropharynx was associated with a significantly lower risk of death than SCC [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Another study conducted by Shen et al analyzed a cohort of 1163 patients diagnosed with primary BSCC in the lip, oral cavity, oropharynx, hypopharynx, and larynx. They reported that the five-year cumulative incidence of cause-specific mortality following the diagnosis of head and neck BSCC was 26.5%. Additionally, they reported that advanced age, larger tumor size, tumor location in the hypopharynx and larynx, lymph node involvement, distant metastasis, and the absence of radiotherapy treatment were positively associated with cause-specific mortality [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eWhile BSCC is defined by the World Health Organization as an aggressive subtype of SCC \u003csup\u003e16\u003c/sup\u003e, our study suggests that when located in different head and neck sites, BSCCs exhibit more favorable clinical outcomes and survival than conventional SCCs found in the same anatomical region \u003csup\u003e17\u003c/sup\u003e. However, this aggressiveness may be attributed to the heightened mitotic activity of undifferentiated basaloid cells. Patients typically present at advanced stages, potentially indicative of the aggressive nature of these cases \u003csup\u003e18\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eOur analysis revealed that a male predominance in BSCC occurred at various head and neck sites, with more than 80% of patients being males, with a mean age of 60 years. However, compared with females, males had a lower overall hazard of death in both samples. Both BSCC and conventional SCC are predominant representations of white ethnicity among their patient populations. Nevertheless, when considering patients of different ethnic backgrounds, those with SCC presented with a slightly greater prevalence of black and Asian/pacific Islander ethnicities than did those with BSCC. While both cancers had the highest prevalence in the \u0026ldquo;Oral Cavity\u0026rdquo;, followed by \u0026ldquo;Waldeyer\u0026rsquo;s Ring \u0026amp; Tonsils,\u0026rdquo; BSCC had a slightly lower incidence across other anatomical sites than did SCC. BSCC patients presented higher grades than did SCC patients, which coincides with previous studies [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. The analysis of treatment modalities (surgery, radiation, surgery\u0026thinsp;+\u0026thinsp;radiation, and chemotherapy) revealed differences in the management of SCC and BSCC patients. SCC patients tend to receive surgery at higher rates than BSCC patients do, whereas BSCC patients have slightly higher rates of radiation therapy, combined surgery and radiation, and chemotherapy, suggesting that surgery is the first line of treatment for SCC and that radiation is the first line of BSCC treatment.\u003c/p\u003e \u003cp\u003eAfter adjusting for other variables, our multivariate analysis revealed that age was not independently associated with OS in the whole cohort. Conversely, other variables, including sex, ethnicity, primary site, grade, stage, surgery, and radiation, demonstrated independent associations with survival, indicating their impact on survival outcomes.\u003c/p\u003e \u003cp\u003eCompared with females, males had a 21% lower hazard; thus, they had greater survival rates than did their counterparts did, and those from nonwhite ethnic backgrounds experienced poorer survival outcomes. Notably, BSCC patients with primary tumors located in the oral cavity, Waldeyer\u0026rsquo;s ring and tonsils presented superior survival rates, whereas those with tumors in the hypopharynx presented the lowest OS compared with those with tumors in the nasopharynx. Moreover, patients who underwent surgical intervention, received radiation therapy or both presented increased survival rates.\u003c/p\u003e \u003cp\u003eBSCC patients were more likely to receive multimodal therapy than SCC patients were. This suggests frequent indications of more aggressive treatment on the basis of the histological type and fear of serious complications, which are strongly enhanced by classical definitions of BSCC variants. Owing to high-risk features such as extracapsular spread and margin status, the SEER database does not provide [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eKnown for its aggressive nature and dismal prognosis, BSCC may react differently to treatment than SCC, especially in areas such as the larynx, hypopharynx, and oropharynx. Surgery is still the mainstay for localized disease and frequently provides the best chance of recovery, particularly when paired with adjuvant radiation or chemoradiotherapy in cases that have high-risk characteristics like extracapsular expansion or positive margins. However, studies indicate that BSCC may respond less well to radiation alone than SCC, possibly because of its different molecular profile. Chemoradiotherapy is commonly used for advanced or incurable cases.\u003c/p\u003e \u003cp\u003eChemotherapy, either as induction therapy or in combination with radiation, should also be investigated further because it may enhance locoregional control and survival in BSCC, which frequently manifests at an advanced stage. In order to improve therapy approaches for these histologically different yet clinically difficult cancers, the publication may help clarify how these treatment approaches affect survival differently in BSCC versus SCC across different anatomical subsites.\u003c/p\u003e \u003cp\u003eSome potential limitations in our study should be acknowledged. First, our dataset lacks information on HPV status, a factor known to positively influence the prognosis of patients diagnosed with BSCC \u003csup\u003e20,21\u003c/sup\u003e..\u003c/p\u003e \u003cp\u003eAlthough HPV data have been available in the SEER database since 2004, they are frequently recorded as 'unknown' for a significant proportion of head and neck cancer patients.\u003c/p\u003e \u003cp\u003eThere is an association between BSCC and HPV, especially HPV-16, and HPV testing is considered an important test for determining the prognosis and possible treatment plans in BSCC patients [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. According to Begum et al., in situ hybridization is better than PCR-based techniques for determining HPV16 status [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eHowever, P16 expression is not always a reliable marker for HPV infection in oral BSCC patients. Moreover, the prevalence of HPV in BSCC depends mainly on the site, as oropharyngeal BSCC is more common than non-oropharyngeal BSCC. Moreover, compared with HPV-negative BSCC, HPV-positive BSCC has superior survival rates and a superior response to chemoradiotherapy, particularly in the oropharynx [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAccording to the WHO Blue Book, basaloid squamous cell carcinoma (BSCC) is a unique condition that is mainly found in the larynx and hypopharynx. It is distinguished by basaloid cells and a component of the stromal basement membrane. However, despite their different biological activity and prognosis, HPV-related non-keratinizing oropharyngeal cancers might be mistakenly categorized as BSCC, leading to diagnostic discrepancies. This emphasizes how crucial it is to differentiate between HPV-related oropharyngeal carcinomas and genuine, HPV-unrelated BSCC in order to do an appropriate survival analysis.\u003c/p\u003e \u003cp\u003eAdditionally, we did not explore the potential relationship between BSCC in the head or neck and the use of alcohol and tobacco for the same reason, both of which have been reported to be associated with BSCC [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. We recommend further studies to investigate the disease-specific survival of each site separately.\u003c/p\u003e"},{"header":"5. Conclusion","content":"\u003cp\u003eOur study comprises the most extensive cohort of patients diagnosed with BSCC in the head and neck. These findings indicate that patients with BSCC have a better prognosis concerning OS than do individuals diagnosed with conventional SCC, even though BSCC tends to be associated with higher tumor grades. Moreover, our analysis suggested that surgical intervention or radiation therapy may confer survival advantages to patients diagnosed with BSCC in the head and neck. Future research should cover each site separately.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eBSCC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eBasaloid squamous cell carcinoma\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSCC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003esquamous cell carcinoma\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eOS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eoverall survival\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eHPV\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ehuman papillomavirus\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSEER\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eSurveillance, Epidemiology, and End Results database\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eNCI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eNational Cancer Institute\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eNIH\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eNational Institutes of Health\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eICD-O-3\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eInternational Classification of Diseases for Oncology, 3rd Edition\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eNOS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eNot otherwise specified\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eEOD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eExtent of disease\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSTORBE\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eStrengthening the reporting of observational studies in epidemiology\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e \u003cp\u003eAnalyses from the SEER database are exempt from review by the institutional review board at Suez Canal University, given the deidentified data of the patients.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eConsent for publication\u003c/strong\u003e \u003cp\u003eNot applicable.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eCompeting interests\u003c/strong\u003e \u003cp\u003eThe authors have no relevant financial or non-financial interests to disclose.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eNo funding was received for conducting this study.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eAuthors' contributionsRW: Conceptualization, manuscript writing, data curation.AE: Conceptualization, manuscript writing, data curation.MA: Conceptualization, manuscript writing, data curation.AA: Conceptualization, manuscript writing, data curation.AS: Manuscript writing, editing, and revision.All the authors have read and approved the final manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgments\u003c/h2\u003e \u003cp\u003eNot applicable.\u003c/p\u003e\u003ch2\u003eAvailability of data and materials\u003c/h2\u003e \u003cp\u003eThe datasets generated and/or analyzed during the current study are publicly available at \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://seer.cancer.gov/\u003c/span\u003e\u003cspan address=\"https://seer.cancer.gov/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eThariat J, Badoual C, Faure C, Butori C, Marcy PY, Righini CA (2010) Basaloid squamous cell carcinoma of the head and neck: role of HPV and implication in treatment and prognosis. J Clin Pathol 63:857\u0026ndash;866\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEren˜o C, Gaafar A, Garmendia M, Etxezarraga C, Bilbao FJ, Lo\u0026acute;pez JI (2008) Basaloid squamous cell carcinoma of the head and neck: a clinicopathological and follow-up study of 40 cases and review of the literature. Head Neck Pathol 2:83\u0026ndash;91\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChoussy O, Bertrand M, Francxois A, Blot E, Hamidou H, Dehesdin D (2011) Basaloid squamous cell carcinoma of the head and neck: report of 18 cases. J Laryngol Otol 125(6):608\u0026ndash;613\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVasudev P, Boutross-Tadross O, Radhi J (2009) Basaloid squamous cell carcinoma: two case reports. Cases J 2:9351\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFritsch VA, Lentsch EJ (2014) Basaloid squamous cell carcinoma of the head and neck: location means everything. J Surg Oncol 109(6):616\u0026ndash;622\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePatel PN, Mutalik VS, Rehani S, Radhakrishnan R (2013) Basaloid squamous cell carcinoma of oral cavity with incongruent clinical course. \u003cem\u003eBMJ case reports\u003c/em\u003e. ; 2013\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSurveillance E, Results E (SEER) Program (eds) (2015) Surveillance, Epidemiology, and End Results (SEER) Program (www.seer.cancer.gov) SEER*Stat Database: Incidence - SEER 18 Regs Research Data\u0026thinsp;+\u0026thinsp;Hurricane Katrina Impacted Louisiana Cases, Nov 2015 Sub (1973\u0026ndash;2013 varying) - Linked To County Attributes - Total U.S., 1969\u0026ndash;2014 Counties, National Cancer Institute, DCCPS, Surveillance Research Program, Surveillance Systems Branch, released April 2016, based on the November submission\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWorld Health Organization (2013) International Classification of Diseases for Oncology, 3rd Edition (ICD-O-3)\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003evon Elm E, Altman DG, Egger M et al (2008) The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. J Clin Epidemiol 61(4):344\u0026ndash;349\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFritsch VA, Lentsch EJ (2013) Basaloid squamous cell carcinoma of the oropharynx: an analysis of 650 cases. Otolaryngol Head Neck Surg 148(4):611\u0026ndash;618\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMoro-Sibilot D, Lantuejoul S, Diab S et al (2008) Lung carcinomas with a basaloid pattern: a study of 90 cases focusing on their poor prognosis. Eur Respir J 31(4):854\u0026ndash;859\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEre\u0026ntilde;o C, Gaafar A, Garmendia M, Etxezarraga C, Bilbao FJ, L\u0026oacute;pez JI (2008) Basaloid squamous cell carcinoma of the head and neck: a clinicopathological and follow-up study of 40 cases and review of the literature. Head Neck Pathol 2(2):83\u0026ndash;91\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eThariat J, Ahamad A, El-Naggar AK et al (2008) Outcomes after radiotherapy for basaloid squamous cell carcinoma of the head and neck: a case\u0026ndash;control study. Cancer 112(12):2698\u0026ndash;2709\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLinton OR, Moore MG, Brigance JS, Gordon CA, Summerlin DJ, McDonald MW (2013) Prognostic significance of basaloid squamous cell carcinoma in head and neck cancer. JAMA Otolaryngol Head Neck Surg 139(12):1306\u0026ndash;1311\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShen W, Sakamoto N, Yang L (2018) Cause-specific mortality prediction model for patients with basaloid squamous cell carcinomas of the head and neck: a competing risk analysis. J Cancer 9(21):4009\u0026ndash;4017\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEI-Naggar AK, Chan JK, C. G, randis JR, Takata T, Slootweg PJ (eds) (2017)\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eThompson L (2006) World Health Organization classification of tumors: pathology and genetics of head and neck tumors. Ear Nose Throat J 85(2):74\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJain N, Raut T, Keshwar S, Shrestha A, Jaisani MR, Paudel D (2023) Histopathological Characterization of a Series of Oral Basaloid Squamous Cell Carcinoma. Case Rep Dent 2023:6036567\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBarnes C, Eveson J, Reichart P et al (2005) Pathology and Genetics: Head and Neck Tumors: World Health Organization Classification of Tumors. IARC, Lyon, France\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBegum S, Westra WH (2008) Basaloid squamous cell carcinoma of the head and neck is a mixed variant that can be further resolved by HPV status. Am J Surg Pathol 32(7):1044\u0026ndash;1050\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChernock RD, Lewis JS, Zhang Q, El-Mofty SK (2010) Human papillomavirus-positive basaloid squamous cell carcinomas of the upper aerodigestive tract: a distinct clinicopathologic and molecular subtype of basaloid squamous cell carcinoma. Hum Pathol 41(7):1016\u0026ndash;1023\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFriedrich RE, Sperber C, J\u0026auml;kel T, R\u0026ouml;ser K, L\u0026ouml;ning T (2010) Basaloid lesions of oral squamous epithelial cells and their association with HPV infection and P16 expression. Anticancer Res 30(5):1605\u0026ndash;1612\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBegum S, Westra WH (2008) Basaloid squamous cell carcinoma of the head and neck is a mixed variant that can be further resolved by HPV status. Am J Surg Pathol 32(7):1044\u0026ndash;1050\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJacobi C, Ayx I, Fritsche K, Piontek G, Hoffmann D, Weirich G, Knopf A (2015) Potential impact of human papilloma virus on survival of basaloid squamous carcinoma of the head and neck. Oncotarget 6:3462\u0026ndash;3470\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVasudev P, Boutross-Tadross O, Radhi J (2009) Basaloid squamous cell carcinoma: two case reports. Cases J 2:9351\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWoolgar JA, Lewis JS Jr, Devaney KO et al (2011) Basaloid squamous cell carcinoma of the upper aerodigestive tract: a single squamous cell carcinoma subtype or two distinct entities hiding under one histologic pattern? Eur Arch Otorhinolaryngol 268(2):161\u0026ndash;164\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"SEER database, basaloid, survival, squamous cell carcinoma, head and neck","lastPublishedDoi":"10.21203/rs.3.rs-6189154/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6189154/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eBasaloid squamous cell carcinoma (BSCC) is known as an aggressive variant of squamous cell carcinoma (SCC) with lower survival rates, mostly because of the increased incidence of distant metastases. Our objective was to provide an update on the clinicopathological presentation and prognosis of BSCC.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA total of 3,327 BSCC patients and 84,724 conventional-type SCC patients were identified via the Surveillance, Epidemiology, and End Results database. Clinicopathologic data were compared via chi-square analysis. Kaplan\u0026ndash;Meier analysis was used to estimate overall survival (OS), and the independent effect of BSCC on OS was assessed via multivariate regression analysis.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003e The oral cavity was the most common site for BSCC and SCC (45.3%). More BSCC patients presented with advanced-stage disease (87.8% vs. 79.3%, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Multivariate analysis revealed that OS was significantly better in the BSCC group when the tumours were located in the tonsils, followed by the oral cavity, oropharynx and nasopharynx. OS was also high in patients who underwent curative surgical, radiological or chemotherapy. It was worse for BSCC patients with hypopharyngeal tumours.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eBSCC\u0026rsquo;s propensity for advanced-stage presentation was confirmed in this study. However, BSCC has a better prognosis than conventional-type SCC. Our analysis revealed a male predominance in BSCC, with a mean age of 60. However, males had a lower hazard of death in both samples. Both groups exhibited a predominant representation of white ethnicity.\u003c/p\u003e","manuscriptTitle":"Survival Outcomes of BSCC Variant Compared with SCC of the Head and Neck: A Cross-Sectional SEER-Based Analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-03-17 07:07:13","doi":"10.21203/rs.3.rs-6189154/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"92b6c8de-ddd7-4df6-a2c1-c88d54db7501","owner":[],"postedDate":"March 17th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-03-17T07:07:16+00:00","versionOfRecord":[],"versionCreatedAt":"2025-03-17 07:07:13","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6189154","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6189154","identity":"rs-6189154","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}