HPV-related Sinonasal Carcinoma: Clinicopathologic Features, Diagnostic Utility of p16 and Rb Immunohistochemistry, and EGFR Copy Number Alteration.
- 作者列表："Jiromaru R","Yamamoto H","Yasumatsu R","Hongo T","Nozaki Y","Hashimoto K","Taguchi K","Masuda M","Nakagawa T","Oda Y
:The prevalence and prognostic value of human papillomavirus (HPV) infection and epidermal growth factor receptor (EGFR) alteration in sinonasal squamous cell carcinoma (SNSCC) are not known. The reliability of p16 overexpression as a surrogate for HPV infection in SNSCC is also unclear. We investigated the prognostic and diagnostic significances of HPV infection, EGFR alteration, and p16 expression in SNSCC. We analyzed high-risk HPV infection by HPV-RNA in situ hybridization and EGFR gene copy number gain (CNG) by chromogenic in situ hybridization and by determining the protein expressions of p16, Rb, and EGFR by immunohistochemistry in 101 SNSCC cases. HPV infection (n=9, 8.9%) and p16 overexpression (n=15, 14.9%) were associated with better overall survival (P=0.0042 and 0.005, respectively). The HPV cases were located predominantly at the nasal cavity with nonkeratinizing histology and partial loss of Rb. Notably, 40% (6/15) of p16 SNSCCs were HPV. Two of these cases showed complete loss of Rb expression by immunohistochemistry, suggesting a reason for the above discrepancy. EGFR CNG, detected in 30.5% of the SNSCCs, was correlated with EGFR protein overexpression (P=0.0001). HPV infection and EGFR CNG were mutually exclusive. The HPV/EGFR CNG group had significantly better overall survival than the HPV/EGFR CNG and HPV/EGFR CNG groups (P=0.0471 and 0.0343, respectively). Our results suggest that HPV infection is a favorable prognostic marker in SNSCC, but p16 is not a perfect surrogate marker; the Rb expression pattern may improve the diagnostic accuracy. The molecular subclassification of SNSCCs based on HPV infection and EGFR copy number status might provide important information for therapeutic strategies.
: 鼻腔鼻窦鳞状细胞癌 (SNSCC) 中人乳头瘤病毒 (HPV) 感染和表皮生长因子受体 (EGFR) 改变的患病率和预后价值尚不清楚。p16过度表达作为SNSCC中HPV感染的替代物的可靠性也不清楚。我们研究了SNSCC中HPV感染、EGFR改变和p16表达的预后和诊断意义。采用hpv-rna原位杂交技术分析高危型HPV感染情况，采用显色原位杂交技术分析EGFR基因拷贝数增益 (CNG)，采用免疫组织化学方法检测101例SNSCC中p16、Rb和EGFR的蛋白表达情况。HPV感染 (n = 9，8.9%) 和p16过表达 (n = 15，14.9%) 与较好的总生存期相关 (分别为P = 0.0042和0.005)。HPV病例主要位于鼻腔，具有非角化性组织学和Rb的部分丧失。值得注意的是，40% (6/15) 的p16 snscc是HPV。这些病例中的两个通过免疫组织化学显示Rb表达的完全丧失，表明上述差异的原因。在30.5% 的snscc中检测到EGFR CNG与EGFR蛋白过表达相关 (P = 0.0001)。HPV感染与EGFR CNG相互排斥。HPV/EGFR CNG组的总生存期显著优于HPV/EGFR CNG组和HPV/EGFR CNG组 (分别为P = 0.0471和0.0343)。我们的结果表明，HPV感染是SNSCC的一个良好的预后标志物，但p16不是一个完美的替代标志物; Rb表达模式可能会提高诊断的准确性。基于HPV感染和EGFR拷贝数状态的snscc分子亚型可能为治疗策略提供重要信息。
METHODS:OBJECTIVE:To evaluate long-term global and site-specific health-related quality of life (HRQoL) in patients treated for sinonasal and nasopharyngeal malignancies. STUDY DESIGN:Cross-sectional. METHODS:One hundred fourteen patients with sinonasal and nasopharyngeal malignancies received surgery, radiation, systemic chemotherapy, or a combination thereof, with curative intent. Validated global ([EuroQol-5D] Visual Analogue Scale [EQ-5D VAS]) and disease-specific instruments (MD Anderson Symptom Inventory-Head and Neck [MDASI-HN], Anterior Skull Base Questionnaire [ASBQ]) were administered to patients who were both free of disease and had completed treatment at least 12 months previously. Associations between instruments, instrument domains, and specific clinical parameters were analyzed. RESULTS:The median age was 55 years. The mean EQ-5D VAS, MDASI-22 composite score, and ASBQ score were 74 (standard deviation [SD] 21), 48 (SD 36), and 130 (SD 27), respectively. The most frequently reported high-severity items in MDASI-HN were dry mouth and difficulty tasting food. The most frequently reported high-severity items in ASBQ were difficulty with smell and nasal secretions. Advanced Tumor (T) classification was associated with worse overall ASBQ sum score (P = 0.02). ASBQ performance at home and MDASI-HN drowsy symptom items independently predicted worse global HRQoL as measured by the EQ-5D VAS (P < 0.001). CONCLUSION:Global HRQoL for survivors of sinonasal and nasopharyngeal malignancies after multimodality treatment approximates that of the U.S. population for the same age group. ASBQ and MDASI-HN correlate well with global HRQoL outcomes as measured by EQ-5D VAS. MDASI-HN and ASBQ elicited unique symptoms, highlighting the complex symptom burden experienced by these patients. Further studies should identify patients predisposed to reduced long-term QOL. LEVEL OF EVIDENCE:3 Laryngoscope, 130:86-93, 2020.
METHODS:BACKGROUND:Allergic rhinitis (AR) and asthma are two common chronic diseases that often coexist. There is a need for a validated tool to evaluate HRQoL of Portuguese speakers with asthma and/or rhinitis patients in clinical practice. OBJECTIVES:To adapt and validate RhinAsthma Patient Perspective (RAPP) in Portuguese. METHODS:The RAPP questionnaire was translated into Portuguese. Asthmatics with comorbidities and rhinitis attending the allergy department of Coimbra University Hospital were asked to complete the Portuguese translation of RAPP, in addition to the SF-12, ACT, and a Symptomatologic VAS twice, with a 4-week interval between visits. During Visit 2, a Global Rating Scale (GRS) was completed to assess any change in health status. Scale dimensions, internal consistency and convergent validity, reliability, discriminant ability and responsiveness to change, as well as Minimal Clinical Difference were assessed. RESULTS:Factor and confirmatory analysis confirm the unidimensional structure of the questionnaire. Internal consistency has been shown to be satisfactory (0.82 visit 1 and 0.86 at visit 2). The tool is able to discriminate between patients on the basis of asthma severity, asthma control level, and rhinitis severity; convergent validity showed a significant correlation with SF-2 Physical component (r=-0.46 and 0.42, p at Visits 1 and 2). An ICC of 0.97 and a CCC=0.94 indicate that the tool is highly reliable. Responsiveness was shown in detecting a significant association with GRS changes (r=0.41, p<0.01) and ACT (r=-0.47, p<0.01) but not with VAS. (r=.14, n.s.). MID value was 2 points. CONCLUSIONS:The Portuguese version of RAPP has been demonstrated to have good measurement properties and sensitivity to health changes, which will provide a valid, reliable and standardized HRQoL measurement in patients with asthma and comorbid allergic rhinitis in clinical practice.
METHODS:OBJECTIVE:To characterize treatment delays in sinonasal cancer managed with surgery and adjuvant radiation and determine the associated impact on survival. STUDY DESIGN:Retrospective cohort study. METHODS:We identified adults in the National Cancer Database treated for sinonasal squamous cell carcinoma with definitive surgery followed by adjuvant radiation from 2004 to 2014. We then examined intervals of diagnosis to surgery (DTS), surgery to radiation (SRT), and radiation duration (RTD). Next, we performed recursive partitioning analysis (RPA) to identify thresholds for these treatment intervals that estimated the greatest differences in survival. We determined the association of treatment delay with overall survival using Cox proportional hazards regression. RESULTS:Among 2,267 patients included, median durations of DTS, SRT, and RTD were 32, 49, and 47 days, respectively. Predictors of treatment delay included care transitions, black race, and Medicare insurance. We identified thresholds of 26, 64, and 51 days for DTS, SRT, and RTD, respectively, as estimating the largest survival differences. Delays in SRT (hazard ratio [HR] 1.20; 95% confidence interval [CI], 1.03-1.40), and RTD (HR, 1.27; 95% CI, 1.10-1.46) beyond these thresholds independently predicted mortality. Delay in DTS beyond the RPA-derived threshold was not significantly associated with mortality after adjusting for other covariates. CONCLUSION:Delays in SRT and RTD intervals are associated with decreased overall survival. Median durations may serve as national benchmarks. Treatment delays could be considered quality indicators for sinonasal cancer treated with surgery and adjuvant radiation. LEVEL OF EVIDENCE:NA Laryngoscope, 130:2-11, 2020.