Association of HPV status with survival after surgical salvage of oropharyngeal cancers.

OBJECTIVES: This study used the National Cancer Database to determine the effect of human papillomavirus (HPV) on survival outcomes for recurrent oropharyngeal cancer treated with salvage surgery after initial treatment with radiation therapy or chemoradiation therapy. METHODS: Patients with recurrent oropharyngeal cancer receiving salvage surgery after initial treatment with adjuvant therapy were identified through the National Cancer Database. Demographics, tumor characteristics, and survival data were collected. The data were analyzed to identify factors that may be associated with survival. RESULTS: A total of 169 patients were included, 59% of which were HPV-positive cases and 41% were HPV-negative. On univariate analysis, HPV-positive cases had higher overall survival compared to HPV-negative cases. However, on multivariate analysis, the association with HPV status was no longer statistically significant while positive surgical margins, higher T-stage at initial diagnosis, and a greater comorbidity burden were significantly associated with poorer survival. CONCLUSION: In the salvage setting for treatment of recurrent oropharyngeal squamous cell carcinoma, HPV status may not be associated with improved survival.

Effect of histopathological grade on treatment and survival in base of tongue adenocarcinoma.

OBJECTIVES: The purpose of this study was to investigate survival differences between low-grade and high-grade base of tongue (BOT) adenocarcinoma by examining demographics, tumor characteristics, and treatment modalities. METHODS: The National Cancer Database was queried for patients with BOT adenocarcinoma between 2004 and 2017. Univariate and multivariate analyses were performed for all cases of BOT adenocarcinoma. Subsequent analysis focused on low-grade (grade 1 and grade 2) and high-grade (grade 3 and grade 4) BOT adenocarcinoma. RESULTS: A total of 286 patients with BOT adenocarcinoma were included in the main cohort and divided into low grade (n = 137) and high grade (n = 66). The 5-year overall survival for all patients, low-grade, and high-grade was 67%, 85%, and 58%, respectively. Prognostic factors associated with decreased survival for the main cohort include advanced age (hazard ratio [HR]: 1.04; 95% confidence interval [CI]: 1.02-1.06), non-white race (HR: 1.79; 95% CI: 1.04-3.25), public insurance (HR: 1.79; 95% CI: 1.02-3.14) and high-grade 3,4 (HR: 2.63; 95% CI: 1.51-4.56). The prognostic factor associated with increased survival for the main cohort was surgery (HR: 0.59; 95% CI: 0.36-0.96). Radiotherapy was associated with improved overall survival for high-grade BOT adenocarcinoma (HR: 0.09; 95% CI: 0.02-0.49) but not for low-grade BOT adenocarcinoma (HR: 0.93; 95% CI: 0.38-2.32). CONCLUSIONS: This investigation is the largest to date analyzing the association of treatment modalities with overall survival in BOT adenocarcinoma. Surgery remains standard of treatment, particularly in low-grade cases, with radiotherapy offering additional survival benefit for high-grade BOT adenocarcinoma.

A contemporary analysis of racial disparities in recommended and received treatment for head and neck cancer.

BACKGROUND: Racial disparities in squamous cell carcinoma of the head and neck (HNSCC) negatively affect non-Hispanic black (NHB) patients. This study was aimed at understanding how treatment is prescribed and received across all HNSCC subsites. METHODS: With the National Cancer Database, patients from 2004 to 2014 with surgically resectable HNSCCs, including tumors of the oral cavity (OC), oropharynx (OP), hypopharynx (HP), and larynx (LX), were studied. The treatment received was either upfront surgery or nonsurgical treatment. Treatment patterns were compared according to race and subsite, and how these differences changed over time was evaluated. RESULTS: NHB patients were less likely than non-Hispanic white (NHW) patients to receive surgery across all subsites (relative risk [RR] for OC, 0.87; RR for OP, 0.75; RR for HP, 0.73; RR for LX, 0.87; all P values <.05). They were also more likely to refuse a recommended surgery (RR for OC, 1.50; RR for OP, 1.23; RR for HP, 1.23; RR for LX, 1.34), and this difference was significant except for HP. NHB patients were more likely to not be offered surgery across all subsites (RR for OC, 1.38; RR for OP, 1.07; RR for HP, 1.05; RR for LX, 1.03; all P values <.05). Rates of surgery increased and rates of not being offered surgery declined for both NHB and NHW patients from 2004 to 2014, but the absolute disparities persisted in 2014. CONCLUSIONS: Across all HNSCC subsites, NHB patients were less likely than NHW patients to be recommended for and receive surgery and were more likely to refuse surgery. These differences have closed over time but persist. Enhanced shared decision making may improve these disparities.

Failed larynx preservation and survival in patients with advanced larynx cancer.

PURPOSE: To evaluate the survival benefit of total laryngectomy (TL) after induction chemotherapy in locally advanced laryngeal cancer patients. MATERIALS AND METHODS: This is a retrospective study utilizing the National Cancer Database, which captures >80% of newly diagnosed head and neck squamous cell carcinoma cases in the United States. We included patients diagnosed with advanced stage laryngeal squamous cell carcinoma between 2004 and 2013 (n = 5649) who received either TL (n = 4113; 72.8%) or induction chemotherapy followed by either radiation therapy (n = 1431) or TL (n = 105). Kaplan-Meier curves and Cox proportional hazards regression were used to evaluate overall survival. A Cox regression model was computed to examine how the prognostic impact of treatment differed by clinical stage. RESULTS: In multivariable analysis, when compared to patients receiving TL alone, those receiving induction chemotherapy followed by TL experienced no significant difference in survival (HR 0.85, 95% CI 0.63-1.13), while those receiving induction chemotherapy followed by radiation experienced poorer survival (HR 1.15, 95% CI 1.06-1.26). Induction chemotherapy followed by TL was associated with improved survival compared to induction chemotherapy and radiation (P = .042). Among patients with T4a tumors, TL (P < .001) and induction chemotherapy followed by TL (P = .002) were both associated with improved survival compared to induction chemotherapy and radiation. There were no survival differences between TL and induction chemotherapy followed by TL (HR 0.76, 95% CI 0.52-1.10). CONCLUSIONS: Larynx preservation may be attempted without compromising survival in patients with locally advanced larynx cancer who fail induction chemotherapy and undergo TL.

The national landscape of human papillomavirus-associated oropharynx squamous cell carcinoma.

The head and neck squamous cell carcinoma (HNC) landscape is evolving with human papillomavirus (HPV) being a rising cause of oropharynx carcinoma (OPC). This study seeks to investigate a national database for HPV-associated oropharynx carcinoma (HPV-OPC). Using the National Cancer Data Base, we analyzed 22,693 patients with HPV-OPC and known HPV status. Chi-square tests and logistic regression models were utilized to examine differences between HPV positive and HPV negative OPC. 14,805 (65.2%) patients were HPV positive. Mean age at presentation was 58.4 years with HPV-HNC patients being 2.8 years younger compared to the HPV-negative cohort (58.4 vs. 61.2 years, p < 0.001). 67.6% of white patients were HPV-positive compared to 42.3% of African American patients and 57.1% of Hispanics (p < 0.001). When combining race and socioeconomic status (SES), we found African American patients in high SES groups had HPV-OPC prevalence that was significantly higher than African American patients in low SES groups (56.9% vs. 36.3%, p < 0.001). Geographic distribution of HPV-OPC was also analyzed and found to be most prevalent in Western states and least prevalent in the Southern states (p < 0.001). The distribution of HPV-OPC is variable across the country and among racial and socioeconomic groups. A broad understanding of these differences in HPV-OPC should drive educational programs and improve clinical trials that benefit both prevention and current treatments.

Adjuvant radiation and survival following surgical resection of sinonasal melanoma.

BACKGROUND: Surgery remains the mainstay of treatment for sinonasal melanoma, but it is often difficult to obtain clear, negative margins. Therefore, patients often receive adjuvant radiation therapy (RT), however its impact on overall survival (OS) is not well understood. METHODS: Patients with surgically resected sinonasal melanoma were identified from the National Cancer Data Base (NCDB, n=696). Kaplan-Meier curves and parametric survival regression were used to analyze the impact of adjuvant RT on OS from surgery. Adjusted time ratios (aTRs) were computed, with values >1 corresponding to improved survival. RESULTS: 399 (57.3%) patients received adjuvant RT. Those receiving RT tended to be younger but with more advanced disease and greater likelihood of positive margins, compared to those receiving no adjuvant therapy. Median survival was 25.0months for those treated with surgery alone, compared to 28.3months for those receiving adjuvant RT (log-rank P=0.408). When adjusting for potential confounders, there was a trend towards greater survival with adjuvant RT (aTR 1.16, 95%CI 0.98-1.37). RT appeared beneficial in those with stage IVB disease (aTR 2.58, 95%CI 1.40-4.75) but not stage IVA (aTR 1.19, 95%CI 0.88-1.61) or III (aTR 0.85, 95%CI 0.65-1.13) disease. In contrast, there were no differences in impact of RT according to margin status (aTR 1.16 for both positive and negative margins). CONCLUSIONS: Adjuvant therapy does not appear to provide a significant survival benefit in resected sinonasal melanomas regardless of margin status, except those with stage IVB disease. Practitioners should carefully consider the added benefit of adjuvant therapy in these patients.

National Trends in the Surgical Treatment of Non-advanced Medullary Thyroid Cancer (MTC): An Evaluation of Adherence with the 2009 American Thyroid Association Guidelines.

BACKGROUND: Medullary thyroid cancer (MTC) represents the third most common type of thyroid cancer, and the prognosis depends on the stage of the disease at diagnosis and completeness of tumor resection. In 2009, the American Thyroid Association (ATA) published guidelines with evidence-based recommendations for the treatment of MTC. This study aimed to determine national adherence rates of the treatment according to the ATA guidelines specific for MTC. METHODS: Patients diagnosed with MTC from 2004 to 2013 were identified from the National Cancer Database. Guideline adherence rates for the treatment of MTC before and after the publication of ATA guidelines were analyzed and compared to determine patient and clinical variables that affected treatment. RESULTS: A total of 3693 patients diagnosed with MTC were identified. We found 60.3 % of the patients had localized MTC and 39.7 % had regional metastases. Older age, female sex and having Medicaid or being uninsured were directly correlated with more advanced disease upon diagnosis (p < 0.001). Overall, a greater proportion of patients received care in accordance with the recommendations following the ATA guidelines' publication in 2009: 61.4 % of patients treated between 2004 and 2008 versus 66.8 % of patients treated between 2009 and 2013 received care in accordance with the recommendations (p < 0.01). Factors such as older age, African American race, localized disease at diagnosis, lower estimated median zip code household income and being treated in a community versus an academic hospital were associated with a lower likelihood of receiving care in accordance with the guidelines. CONCLUSION: Adherence rates to the ATA recommendations for the treatment of MTC increased modestly following the publication of guidelines in 2009 with the largest increase seen in community hospitals. Being older, African American, diagnosed with localized disease and treated in a community hospital rather than in an academic institution was correlated with a lower likelihood of receiving treatment in accordance with the guidelines. Efforts should be made to continuously increase the adherence rates to the MTC ATA guidelines and to decrease socioeconomic disparities that continue to exist in the treatment of MTC.

A Contemporary Analysis of Surgical Trends in the Treatment of Squamous Cell Carcinoma of the Oropharynx from 1998 to 2012: A Report from the National Cancer Database.

BACKGROUND: This study examined surgical trends for oropharynx squamous cell carcinoma (OPC) from 1998 to 2012, with a post-2009 focus coinciding with the Food and Drug Administration (FDA) approval of transoral robotic surgery (TORS). METHODS: Using the National Cancer Data Base, the study analyzed 84,449 patients with stage I-IVB OPC. χ (2) tests and logistic regression models were used to examine surgical trends. RESULTS: The use of surgery decreased from 41.4 % in 1998 to 30.4 % in 2009 (p < 0.001). The surgical trends reversed and in 2012 increased to 34.8 % (p < 0.001). There was much variation in surgery in 2012 between American Joint Committee on Cancer stages, with 80.2 % of stage I patients receiving surgery compared with 54.0 % of stage II patients, 36.8 % of stage III patients, and 28.5 % of stage IV patients (p < 0.001). Black patients with high socioeconomic status (SES) showed lower use of surgery (25.3 %) compared to low SES white (32.3 %) and low SES Hispanic patients (27.3 %) (p < 0.001). The highest surgical rates were noted in the West North Central region and lowest rates were observed in the New England and South Atlantic regions. Between 2009 and 2012, independent predictors of surgical treatment included young age, female gender, white or Hispanic race, high SES, private insurance, academic hospitals, hospitals in the West North Central region, residence more than 75 miles from the hospital, increasing comorbidities, stage I disease, and tonsil origin (all p < 0.05). CONCLUSION: Since FDA approval of TORS in 2009, surgical rates have increased with multiple socioeconomic and regional factors affecting patient selection. This study provides a basis for further investigation into factors involved in decision making for OPC patients.

Racial Disparities in Head and Neck Cancer: It's Not Just About Access.

OBJECTIVE: Medical literature identifies stark racial disparities in head and neck cancer (HNC) in the United States, primarily between non-Hispanic white (NHW) and non-Hispanic black (NHB) populations. The etiology of this disparity is often attributed to inequitable access to health care and socioeconomic status (SES). However, other contributors have been reported. We performed a systematic review to better understand the multifactorial landscape driving racial disparities in HNC. DATA SOURCES: A systematic review was conducted in Covidence following Preferred Reporting Items for Systematic Reviews and Meta-analyses Guidelines. A search of PubMed, SCOPUS, and CINAHL for literature published through November 2022 evaluating racial disparities in HNC identified 2309 publications. REVIEW METHODS: Full texts were screened by 2 authors independently, and inconsistencies were resolved by consensus. Three hundred forty publications were ultimately selected and categorized into themes including disparities in access/SES, treatment, lifestyle, and biology. Racial groups examined included NHB and NHW patients but also included Hispanic, Native American, and Asian/Pacific Islander patients to a lesser extent. RESULTS: Of the 340 articles, 192 focused on themes of access/SES, including access to high-quality hospitals, insurance coverage, and transportation contributing to disparate HNC outcomes. Additional themes discussed in 148 articles included incongruities in surgical recommendations, tobacco/alcohol use, human papillomavirus-associated malignancies, and race-informed silencing of tumor suppressor genes. CONCLUSION: Differential access to care plays a significant role in racial disparities in HNC, disproportionately affecting NHB populations. However, there are other significant themes driving racial disparities. Future studies should focus on providing equitable access to care while also addressing these additional sources of disparities in HNC.

A Nationwide Analysis of Head and Neck Fibromatoses.

BACKGROUND: Head and neck fibromatoses (HNFs) are a rare, diverse group of soft tissue tumors characterized by an abnormal proliferation of fibroblasts. Available literature on these tumors is limited to case reports and small single-institutional studies. OBJECTIVE: We aim to provide demographic, socioeconomic, tumor-related, and treatment characteristics of HNFs. DESIGN: Retrospective cohort analysis using the National Cancer Database (NCDB). METHODS: The NCDB was queried for fibromatosis-related histologic codes located within the head and neck region. Various factors were analyzed. Univariate and multivariate survival analyses were performed. RESULTS: Between 2004 and 2016, 130 patients were included in the analyses. Average age was 57.4 years old with a predominance of White (83.6%) males (61.5%). Non-desmoid HNFs accounted for 60%-70% of the tumors. The salivary gland was the most common location (38.5%) and more than half of the tumors were high grade. The majority were treated surgically (90.8%) and 25% had positive margins. Mean and median overall survival (OS) were 98.9 and 135.4 months, respectively. Surgery is associated with better OS than nonsurgical alternatives. Addition of adjuvant treatments was not associated with differences in survival. CONCLUSION: In the largest study to date, we describe demographic, socioeconomic, tumor-related, and treatment patterns of patients with this rare disease. These tumors are most frequently present in middle-aged males with high-grade histology. Most are treated surgically and positive surgical margins are common. Surgery has better OS than nonsurgical alternatives. While adjuvant radiation has become more common, we found no difference in survival compared to surgery alone. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:2228-2235, 2024.

Oral cancer incidence rate is associated with access to dental care: City and statewide analyses.

INTRODUCTION: Access to dental care may affect diagnosis of oral squamous cell carcinoma (OSCC). We tested whether the incidence rate of OSCC is higher in regions with less dental care access in the city of Chicago and state of Illinois. STUDY DESIGN: Ecological cohort. SETTING: Population, outpatients, and inpatients. METHODS: We extracted 5-year averages of the state-wide county-level and city-level OSCC incidence rates from 2015 to 2019 from the Illinois Department of Public Health. Dental care access information was also collected for each county for the same period, as well as the percentage of people that had ≥1 visit to a dentist in the previous year in Chicago. Multivariate Poisson regression was used to investigate the relationship between county-level access to dental care (and city-level dentist visits) and OSCC incidence rate, controlling for confounders, with additional flexible semiparametric models for confirmatory sensitivity analysis. RESULTS: In Illinois, higher 5-year incidence rate of OSCC was significantly associated with low access to dental care by county (IRR = 0.96, 95% CI 0.91, 0.98). Southern/southwestern counties had higher incidence rates of OSCC (15.5%-28.4%) and the lowest rates of dental care access (47.5%-69.2%) compared to northern counties (10.3%-15% and 55.4%-80.6%, respectively). In Chicago, people with more dentist visits had a reduced chance of being diagnosed with OSCC (IRR = 0.97, 95% CI 0.91, 0.99), consistent with state-wide analyses. CONCLUSION: OSCC incidence rate is closely associated with poor local dental healthcare access in a major state and urban city. Increasing dental access could improve cancer outcomes via improved oral health and earlier detection.

Air pollution is associated with increased incidence-rate of head and neck cancers: A nationally representative ecological study.

INTRODUCTION: Early studies show conflicting findings regarding particulate matter ≤ 2.5 µm in diameter (PM2.5) exposure and development of head and neck cancers (HNC). We analyzed the relationship between PM2.5 exposure and various types of HNC in a nationally representative ecological sample. METHODS: We determined HNC incidence in 608 US counties from 2011 to 2019 using the Surveillance, Epidemiology and End Results (SEER) Program from the National Cancer Institute. We also collected information on sociodemographic factors from SEER and data on smoking and alcohol intake from CDC data frames (county level). PM2.5 exposure levels were estimated using satellite and meteorological data via previously validated general additive models. Flexible semi-nonparametric regression models were used to test the relationship between PM2.5 exposure levels and HNC incidence, adjusting for demographics, socioeconomic factors, and comorbidity. RESULTS: Increased PM2.5 exposure levels were associated with higher incidence-rates of oral cavity and pharyngeal cancers controlling for confounders in our primary analyses (IRR = 1.04, 95 % CI 1.01, 1.07, p = 0.02 per 1 µg/m3 increase in PM2.5). This relationship was maintained after adjusting for multiple testing (Holm s method, p = 0.04) and in ordinary least squares (OLS) regression (ß = 0.17, 95 % CI 0.01, 0.57, p = 0.01). Increased exposure was also associated with other HNC: esophagus (IRR = 1.06, 95 % CI 1.01, 1.11, p = 0.02), lip (IRR = 1.16, 95 % CI 1.03, 1.31, p = 0.01), tonsil (IRR = 1.10, 95 % CI 1.03, 1.16, p < 0.01). However, these relationships were not maintained in secondary analyses. CONCLUSIONS: This nationally representative ecological study shows that increased levels of air pollution are associated with increased incidence of overall oral cavity and pharyngeal cancers in the US.

Utility of TTMV-HPV DNA in resolving indeterminate findings during oropharyngeal cancer surveillance.

OBJECTIVES: Clinical and imaging examinations frequently have indeterminate results during cancer surveillance, which can lead to overtreatment and cause psychological and financial harm to the patient. This study addresses the critical need to enhance diagnostic precision and decision-making in the management of HPV-associated oropharyngeal cancer. This study evaluated the utility of tumor tissue-modified viral (TTMV)-HPV DNA to resolve indeterminate disease status following definitive treatment for HPV-associated oropharyngeal cancer. MATERIALS AND METHODS: In this retrospective cohort, patients treated for HPV-associated oropharyngeal cancer at eight U.S. institutions and who received one or more TTMV-HPV DNA tests during post-treatment surveillance between February 2020 and January 2022 were included. RESULTS: Among 543 patients, 210 patients (38.7%; 210/543) experienced one or more clinically indeterminate findings (CIFs) during surveillance, with 503 CIFs recorded. Of those patients with an "indeterminate" disease status at a point during surveillance, 79 were associated with contemporaneous TTMV-HPV DNA testing. TTMV-HPV DNA testing demonstrated high accuracy (97.5%; 77/79) in correctly determining recurrence status. Patients whose disease status was "indeterminate" at the time of a positive TTMV-HPV DNA test were clinically confirmed to recur faster than those whose disease status was "no evidence of disease." Only 3% of patients (17/543) experienced indeterminate TTMV-HPV DNA tests during surveillance. Discordance between TTMV-HPV DNA tests and clinical results was minimal, with only 0.6% (3/543) of patients showing positive tests without recurrence. CONCLUSION: Our findings support the utility of circulating TTMV-HPV DNA in resolving indeterminate disease status and informing the subsequent clinical course.

International Consensus Statement on Allergy and Rhinology: Sinonasal Tumors.

BACKGROUND: Sinonasal neoplasms, whether benign and malignant, pose a significant challenge to clinicians and represent a model area for multidisciplinary collaboration in order to optimize patient care. The International Consensus Statement on Allergy and Rhinology: Sinonasal Tumors (ICSNT) aims to summarize the best available evidence and presents 48 thematic and histopathology-based topics spanning the field. METHODS: In accordance with prior International Consensus Statement on Allergy and Rhinology documents, ICSNT assigned each topic as an Evidence-Based Review with Recommendations, Evidence-Based Review, and Literature Review based on the level of evidence. An international group of multidisciplinary author teams were assembled for the topic reviews using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses format, and completed sections underwent a thorough and iterative consensus-building process. The final document underwent rigorous synthesis and review prior to publication. RESULTS: The ICSNT document consists of four major sections: general principles, benign neoplasms and lesions, malignant neoplasms, and quality of life and surveillance. It covers 48 conceptual and/or histopathology-based topics relevant to sinonasal neoplasms and masses. Topics with a high level of evidence provided specific recommendations, while other areas summarized the current state of evidence. A final section highlights research opportunities and future directions, contributing to advancing knowledge and community intervention. CONCLUSION: As an embodiment of the multidisciplinary and collaborative model of care in sinonasal neoplasms and masses, ICSNT was designed as a comprehensive, international, and multidisciplinary collaborative endeavor. Its primary objective is to summarize the existing evidence in the field of sinonasal neoplasms and masses.

A nationwide analysis of salvage surgery for laryngeal cancer in the elderly.

BACKGROUND: We aim to describe outcomes of elderly patients undergoing salvage surgery for laryngeal cancer and to characterize the interplay of age with various other factors in this growing population. METHODS: Using the National Cancer Database, we identified cases of salvage laryngectomy in patients who failed chemoradiation. An age cutoff of 70 years was used to separate subjects into two groups. Various factors were compared. RESULTS: Of the 825 patients included, 166 (20.1%) were elderly. Elderly patients had worse overall survival (p = 0.001), higher 30-day and 90-day mortality (p = 0.006, p < 0.001), and a longer length of stay (LOS) (p = 0.015). LOS over 1 week was associated with worse survival (p = 0.032). CONCLUSION: Elderly patients had worse overall perioperative survival than their younger counterparts. LOS and 30-day readmissions were associated with higher risk of mortality in this group. We provide a contemporary set of relevant information for head and neck cancer providers to consider in this growing population.

Negative Predictive Value of Circulating Tumor Tissue Modified Viral (TTMV)-HPV DNA for HPV-driven Oropharyngeal Cancer Surveillance.

PURPOSE: Human papillomavirus (HPV) is causally linked to oropharyngeal squamous cell carcinoma (OPSCC). Consensus guidelines recommend clinical exams and imaging in decreasing frequency as part of posttreatment surveillance for recurrence. Plasma tumor tissue modified viral (TTMV)-HPV DNA testing has emerged as a biomarker which can inform disease status during surveillance. EXPERIMENTAL DESIGN: This retrospective observational cohort study involved 543 patients who completed curative-intent therapy for HPV-associated OPSCC between February 2020 and January 2022 at eight U.S. cancer care institutions. We determined the negative predictive value (NPV) of TTMV-HPV DNA for recurrence when matched to physician-reported clinical outcome data (median follow-up time: 27.9 months; range: 4.5-154). RESULTS: The cohort included mostly men with a median age of 61 who had locoregionally advanced disease. HPV status was determined by p16 positivity in 87% of patients, with a positive HPV PCR/ISH among 55%; while pretreatment TTMV-HPV DNA status was unknown for most (79%) patients. Patients had a mean of 2.6 tests and almost half had three or more TTMV-HPV DNA results during surveillance. The per-test and per-patient sensitivity of the assay was 92.5% [95% confidence interval (CI): 87.5-97.5] and 87.3% (95% CI: 79.1-95.5), respectively. The NPV for the assay was 99.4% (95% CI: 98.9-99.8) and 98.4% (95% CI: 97.3-99.5), respectively. CONCLUSIONS: TTMV-HPV DNA surveillance testing yields few false negative results and few missed recurrences. These data could inform decisions on when to pursue reimaging following first disease restaging and could inform future surveillance practice. Additional study of how pretreatment TTMV-HPV DNA status impacts sensitivity for recurrence is needed.

Prognosis and risk factors for early-stage adenoid cystic carcinoma of the major salivary glands.

BACKGROUND: Adenoid cystic carcinoma (ACC) is characterized by slow growth, frequent local recurrences, and distant metastasis (DM). However, these findings frequently are reported in patients with advanced-stage tumors, but the outcomes of early-stage tumors are poorly defined. We sought to evaluate the risk factors for the development of DM in early-stage ACC. METHODS: We retrospectively reviewed the charts of 60 patients who were diagnosed with clinical early-stage (T1-2/N0) ACC to determine the risk factors for development of DM and survival of these patients. RESULTS: DM was detected in 12 (20%) of the patients, with a median latency of 31.5 months after diagnosis. Univariate analysis revealed that DM was associated with age ≥45 years, pathologically positive lymph nodes, extracapsular spread (ECS) from lymph nodes, high-grade histology, and solid tumor subtype. Multivariate analysis revealed solid tumor subtype and ECS to be significantly associated with DM. Disease-specific survival rates at 5 and 10 years for patients with DM were 80% and 40%, respectively, and were both 100% for patients without DM. CONCLUSION: Although the majority of patients with clinical early-stage ACC of the major salivary glands have favorable prognosis, a significant percentage of patients will develop DM. Solid tumor subtype and nodal ECS were independent predictors of DM in early-stage ACC of major salivary glands. Other clinical and pathological variables may also contribute. These subgroups had poor overall and disease-specific survival. Such patients should be observed closely for the development of DM. Systemic therapy should be considered at the time of diagnosis.

Functional relevance of miRNA sequences in human disease.

MicroRNA (miRNA) processing in the cytoplasm produces a miRNA duplex containing the forward, miRNA strand and the reverse, miRNA strand, which was thought to be degraded. However, recent evidence is challenging this dogma that miRNA is simply a non-functional byproduct of miRNA biogenesis. We present a comprehensive review of evidence that miRNA plays a significant role in cellular function and assembled a table outlining all of the publications before September 2011 that have reported on miRNA activity in human disease. Furthermore, we will present unexpected diagnostic and therapeutic implications due to the active miRNA status.

Neck Dissection in Salvage Surgery for Larynx Cancer: National Cancer Database Review.

OBJECTIVE: Salvage laryngeal surgery is the preferred treatment after failure of non-surgical treatment of larynx cancer. This study aims to identify the impact of ND in salvage surgery on survival and factors predictive of nodal metastasis. METHODS: The National Cancer Database was used to identify patients who received salvage laryngeal surgery. Demographics, disease characteristics, and survival were compared between the subgroups of patients stratified according to performance of ND and presence of nodal metastasis. RESULTS: Sixty-two percent of patients underwent ND. A total of 26% of patients undergoing ND had nodal metastasis. Younger age and lesser time since radiation were associated with nodal metastasis. While undergoing ND did not significantly affect survival, those with nodal metastasis had poorer survival (P = .001). CONCLUSIONS: Although ND did not show a survival benefit, younger patients and those who have had a shorter time elapsed between the start of radiation and salvage surgery may benefit from the prognostic data provided by ND. Nonetheless, the risks and benefits of elective ND in salvage larynx cancer treatment should be evaluated on an individual case basis as the data do not support a broadly applicable recommendation.

Presence of CrkI-containing microvesicles in squamous cell carcinomas could have ramifications on tumor biology and cancer therapeutics.

Recently, we described a phenomenon whereby apoptotic cells generate and release CrkI-containing microvesicles, which stimulate proliferation in surrounding cells upon contact to compensate for their own demise. We termed these microvesicles "ACPSVs" for Apoptotic Compensatory Proliferation Signaling microvesicles. As immune cells and a majority of current cancer therapeutics destroy tumor cells primarily by apoptosis, we conducted a small pilot study to assess the possibility that ACPSVs may also be generated in squamous cell carcinomas. We first evaluated a primary and a metastatic squamous cell carcinoma cancer cell lines for their ability to produce ACPSVs under normal and apoptotic conditions. We next conducted a pilot study to assess the occurrence of ACPSVs in solid tumors extracted from 20 cancer patients with squamous cell carcinomas. Both cancer cell lines produced copious amounts of ACPSVs under apoptotic conditions. Interestingly, the metastatic squamous cell carcinoma cancer cell line also produced high levels of ACPSVs under healthy condition, suggesting that the ability to generate ACPSVs may be hijacked by these cells. Importantly, ACPSVs were also abundant in the solid tumors of all squamous cell carcinoma cancer patients. Detection of ACPSVs in cancer has potentially important ramifications in tumor biology and cancer therapeutics which warrants further investigation.