Head and neck cancers associated with exposure to the September 11, 2001 World Trade Center terrorist attacks

Exposure at the World Trade Center (WTC) terrorist collapse site on September 11, 2001 has been associated with increased cancer risk, though observational studies have identified very few cases of head and neck cancer (HNC) in exposed individuals. Eighty seven patients were identified who presented to our institution with HNC diagnosed from 2002 to 2017 who reported WTC exposure. The annual number and proportion of WTC‐exposed HNC patients has been steadily increasing since 2002, with most cancers developing >10 years following the event. Furthermore, WTC‐exposed patients with human papillomavirus (HPV)‐positive OPC experienced significantly inferior outcomes compared with non‐WTC exposed patients with HPV+ OPC (disease free survival 80.1% vs. 65.6% at 4 years, p = 0.04). This single institution study cannot establish evidence of exposure‐mediated causation but higher recurrence rates in the WTC‐exposed HPV+ OPC population suggest a treatment refractory tumor biology and possible exposure synergism with HPV‐mediated oncogenesis.     

Role of mucosal high‐risk human papillomavirus types in head and neck cancers in central India

Mucosal high‐risk (HR) human papillomaviruses (HPV) cause a subset of head and neck cancers (HNC). The HPV‐attributable fraction of HNC varies substantially between countries. Although HNC has a very high incidence in the Indian subcontinent, information on the contribution of HPV infection is limited. Here, we evaluated the HPV‐attributable fraction in HNC (N = 364) collected in a central region of India. HNC from three different anatomical subsites were included, namely, oral cavity (n = 252), oropharynx (n = 53) and hypopharynx/larynx (n = 59). In this retrospective study, HPV‐driven HNC were defined by presence of both viral DNA and RNA. Overexpression of p16^INK4a was also evaluated. HR‐HPV DNA was detected in 13.7% of the cases; however, only 2.7% were positive for both HPV DNA and RNA. The highest percentage of HPV DNA/RNA double positivity was found in oropharynx (9.4%), followed by larynx (1.7%) and oral cavity (1.6%) (p = 0.02). More than half of HPV DNA/RNA‐positive cases were p16^INK4a‐negative, while a considerable number of HPV RNA‐negative cases were p16^INK4a‐positive (17.9%). HPV16 was the major type associated with HNC (60.0%), although cases positive for HPV18, 35 and 56 were also detected. Our data indicate that the proportion and types of mucosal HR‐HPV associated with HNC in this central Indian region differ from those in other (developed) parts of the world. This may be explained by differences in smoking and/or sexual behaviour compared with North America and northern Europe. Moreover, we show that p16^INK4a staining appeared not to be a good surrogate marker of HPV transformation in the Indian HNC cases.     

Over one‐third of African‐American MGUS and multiple myeloma patients are carriers of hyperphosphorylated paratarg‐7, an autosomal dominantly inherited risk factor for MGUS/MM

As hyperphosphorylated paratarg‐7 (pP‐7) carrier state was shown to be the first molecularly defined autosomal dominantly inherited risk factor for monoclonal gammopathy of unknown significance (MGUS) and multiple myeloma (MM) in a European population, the prevalence of pP‐7 carrier state among African‐Americans who have a significantly higher incidence of MGUS/MM is of interest. We therefore determined pP‐7 carrier state and paraproteins with specificity for P‐7 in African‐American, European and Japanese patients with MGUS/MM and healthy controls. By isoelectric focusing and ELISA, a paratarg‐7‐specific paraprotein and the associated pP‐7 carrier state was observed in 30/81 (37.0%) African‐American, 42/252 (16.7%) European and 7/176 (4.0%) Japanese MGUS/MM patients (p < 0.001). A pP‐7 carrier state was found in 11/100 (11.0%) African‐American, 8/550 (1.5%) European and 1/278 (0.4%) Japanese healthy controls (p < 0.001), resulting in an odds ratio for MGUS/MM of 4.8 (p < 0.001) among African‐American, 13.6 among European (p < 0.001) and 11.5 (p = 0.023) among Japanese carriers of pP‐7. We conclude that pP‐7 carriers are most prevalent among African‐Americans, but a pP‐7 carrier state is the strongest molecularly defined single risk factor for MGUS/MM known to date in all three ethnic groups. The high prevalence of pP‐7 carriers among African‐American patients emphasizes a predominant role of this genetic factor in the pathogenesis of these diseases. The large number of pP7 African‐American patients and controls should facilitate the identification of the SNP or mutation underlying the pP‐7 carrier state.     

Risk factors and survival by HPV‐16 E6 and E7 antibody status in human papillomavirus positive head and neck cancer

High‐risk human papillomavirus types (HPV‐HR) are associated with head and neck cancer (HNC) risk and better survival. Most patients with HPV‐HR DNA‐positive tumors develop anti‐HPV E6/E7 antibodies; however, it is unclear whether those who mount an immune response have similar risk factors or clinical outcomes as those who do not. HPV‐16 DNA tumor‐positive HNC cases were evaluated for HPV‐16 E6 and E7 antibodies using a GST capture ELISA system. Among 57 HPV‐16 DNA tumor‐positive HNC cases, 67% were detected with HPV‐16 E6 and/or E7 antibodies. Male gender (76% vs. 42%, p = 0.02), younger age (63% vs. 16%, p = 0.001) but not tobacco or alcohol were associated with E6 and/or E7 seropositivity. Seropositivity was associated more often with late stage (76%), poor grade (65%), positive nodes (82%). and in the oropharynx (82%), Median disease‐specific and recurrence‐free survival were longer in E6 and/or E7 seropositive compared to E6/E7‐negative cases (2.2 years vs. 1.4 years, both outcomes), although results were not statistically significant. When examined jointly with p16 expression, E6 and/or E7‐positive/p16‐positive cases had better disease‐specific (2.1 years vs. 1.1 years, p = 0.06) and recurrence‐free (2.3 years vs. 1.1 years, p = 0.03) survival compared to E6‐/E7‐/p16‐ cases. These findings suggest there are 2 distinct HNC patient groups with HPV DNA‐positive tumors, distinguishable by E6 and/or E7 antibody status. Differences in antibody status are associated with distinct risk factors and clinical outcomes. This information can be available as a simple blood test at initial presentation, before the removal of tissue through biopsy or surgery.     

Incidence trends of human papillomavirus‐related head and neck cancer in Taiwan, 1995–2009

Recent studies suggested that human papillomavirus (HPV) is an emerging risk factor of head and neck cancer (HNC), particularly for oropharyngeal cancer. Studies from the West showed a rising trend of HPV‐related HNC despite a decrease of the overall HNC incidence. In contrast, the overall HNC incidence in Taiwan has continued to rise. It is not clear whether the incidence trends of HPV‐related HNC in Taiwan have a similar pattern to those from countries with an overall decreasing incidence of HNC. This study examined the incidence trends of HPV‐related and HPV‐unrelated HNC in Taiwan using data from the Taiwan Cancer Registry. Our results showed that the incidence trends of HPV‐related and HPV‐unrelated HNC in Taiwan both rose during 1995–2009. The incidence of HPV‐related HNC (1.3 per 100,000 in 1995 to 3.3 in 2009, annual percentage change (APC) = 6.9, p < 0.0001) rose more rapidly than the incidence of HPV‐unrelated HNC (10.4 per 100,000 in 1995 to 21.7 in 2009, APC = 5.0, p < 0.0001). The rising trend of HPV‐related HNC was particularly prominent for HNC occurring in tonsil (APC = 8.2, p < 0.0001), in men (APC = 7.5, p < 0.0001), and in those aged between 40 and 50 years (APC = 8.5, p < 0.0001). Although the overall incidence of HNC in Taiwan has continued to increase, the most rapid rise is in the HPV‐related HNC. This suggests that similar to the Western world, HPV‐related HNC is becoming an important public health issue in Taiwan.     

Human papillomavirus and p53 mutations in head and neck squamous cell carcinoma among Japanese population

We aimed to reveal the prevalence and pattern of human papillomavirus (HPV) infection and p53 mutations among Japanese head and neck squamous cell carcinoma (HNSCC) patients in relation to clinicopathological parameters. Human papillomavirus DNA and p53 mutations were examined in 493 HNSCCs and its subset of 283 HNSCCs. Oropharyngeal carcinoma was more frequently HPV‐positive than non‐oropharyngeal carcinoma (34.4% vs 3.6%, P < 0.001), and HPV16 accounted for 91.1% of HPV‐positive tumors. In oropharyngeal carcinoma, which showed an increasing trend of HPV prevalence over time (P < 0.001), HPV infection was inversely correlated with tobacco smoking, alcohol drinking, p53 mutations, and a disruptive mutation (P = 0.003, <0.001, <0.001, and <0.001, respectively). The prevalence of p53 mutations differed significantly between virus‐unrelated HNSCC and virus‐related HNSCC consisting of nasopharyngeal and HPV‐positive oropharyngeal carcinomas (48.3% vs 7.1%, P < 0.001). Although p53 mutations were associated with tobacco smoking and alcohol drinking, this association disappeared in virus‐unrelated HNSCC. A disruptive mutation was never found in virus‐related HNSCC, whereas it was independently associated with primary site, such as the oropharynx and hypopharynx (P = 0.01 and 0.03, respectively), in virus‐unrelated HNSCC. Moreover, in virus‐unrelated HNSCC, G:C to T:A transversions were more frequent in ever‐smokers than in never‐smokers (P = 0.04), whereas G:C to A:T transitions at CpG sites were less frequent in ever‐smokers than in never‐smokers (P = 0.04). In conclusion, HNSCC is etiologically classified into virus‐related and virus‐unrelated subgroups. In virus‐related HNSCC, p53 mutations are uncommon with the absence of a disruptive mutation, whereas in virus‐unrelated HNSCC, p53 mutations are common, and disruptive mutagenesis of p53 is related with oropharyngeal and hypopharyngeal carcinoma.     

Detection of human papillomavirus‐related squamous cell carcinoma cytologically and by in situ hybridization in fine‐needle aspiration biopsies of cervical metastasis

BACKGROUND

Fine‐needle aspiration (FNA) biopsy often is the first diagnostic procedure performed in patients with head and neck masses. When squamous cell carcinoma (SCC) is diagnosed, proper management and improved prognosis depends on identification of the primary tumor. Recent studies have indicated that human papillomavirus (HPV) infection is associated closely with oropharyngeal SCC and that these tumors have a distinct nonkeratinizing morphology. In this study, the authors explored the value of identifying HPV‐related tumors in neck metastases to determine the origin of occult primary head and neck squamous cell carcinoma (HNSCC).

METHODS

Thirty FNA biopsies of neck metastases from patients with HNSCC were recovered from the authors' files from 2004 to 2005. The primary sites included 13 oropharynx, 13 oral cavity, and 4 larynx/hypopharynx. All patients had corresponding tissue samples from the neck mass and the primary carcinoma. The FNA specimens and corresponding tissue samples were classified as either nonkeratinizing SCC (NKSCC) or keratinizing SCC (KSCC). In situ hybridization for HPV (HPV‐ISH) was performed using ethanol‐fixed, Papanicolaou‐stained smears. A positive signal was defined as dark blue or black nuclear dots. Corresponding formalin‐fixed, paraffin‐embedded tissue sections also were processed for HPV‐ISH.

RESULTS

Twenty of the 30 FNA specimens were KSCC, and 10 were NKSCC. Eight of the 10 NKSCCs originated in the oropharynx, and 2 had nonoropharyngeal origin. HPV was detected in 7 of 10 NKSCCs. Ten of 30 (33%) FNA biopsies were positive for HPV, and 9 of those biopsies were metastatic from the oropharynx. Nonkeratinzing morphology or HPV‐positive ISH in FNA samples significantly predicted oropharyngeal origin (P < .0069 and P < .0004, respectively).

CONCLUSIONS

NKSCC in metastatic cervical lymph nodes predicted positive HPV‐ISH and was strongly suggestive of an oropharyngeal primary tumor. Cancer (Cancer Cytopathol) 2008. © 2008 American Cancer Society.     

Head and neck cancer-specific survival based on socioeconomic status in Asians and Pacific Islanders

BACKGROUND:

Lower socioeconomic status (SES) has been linked to higher incidence of head and neck cancer (HNC) and lower survival. However, little is known about the effect of SES on HNC survival in Asians and Pacific Islanders (APIs). This study's purpose was to examine the effect of SES on disease‐specific survival (DSS) and overall survival (OS) in APIs with HNC using population‐based data.

METHODS:

A total of 53,544 HNC patients (4,711 = APIs) were identified from the California Cancer Registry from 1988 to 2007. Neighborhood (block‐group‐level) SES, based on composite Census 1990 and 2000 data, was calculated for each patient based on address at diagnosis, categorized into statewide quintiles, and collapsed into 2 groups for comparison (low SES = quintiles 1‐3; high SES = quintiles 4‐5). DSS and OS were computed by the Kaplan‐Meier method. Adjusted hazards ratios (HR) were estimated using Cox proportional hazards regression models.

RESULTS:

Among APIs, lower neighborhood SES was significantly associated with poorer DSS (HR range for oral cavity, oropharynx, or larynx/hypopharynx cancer, 1.07‐1.34) and OS (HR, 1.13‐1.37) after adjusting for patient and tumor characteristics. Lower SES was significantly associated with poorer survival in API with all HNC sites combined: DSS HR: 1.26 (95% confidence interval [CI], 1.08‐1.48) and OS HR, 1.30 (95% CI, 1.16‐1.45).

CONCLUSIONS:

Neighborhood SES was associated with longer DSS and OS in API with HNC. The effect of SES on HNC survival should be considered in future studies, and particular attention should be paid to clinical care of lower‐SES HNC patients. Cancer 2011. © 2010 American Cancer Society.     

The PD‐1/PD‐L1 axis and human papilloma virus in patients with head and neck cancer after adjuvant chemoradiotherapy: A multicentre study of the German Cancer Consortium Radiation Oncology Group (DKTK‐ROG)

We examined the prognostic role of PD‐1+ and CD8+ tumor infiltrating lymphocytes (TILs), and PD‐L1+ cells in patients with squamous cell carcinoma of the head and neck (SCCHN) treated with surgery and postoperative chemoradiotherapy (CRT). FFPE samples from 161 patients were immunohistochemically stained for PD‐1, CD8 and PD‐L1. The immune marker expression was correlated with clinicopathologic characteristics, and overall survival (OS), local progression‐free survival (LPFS) and distant metastases free‐survival (DMFS), also in the context of HPV16 DNA/p16 status. The median follow‐up was 48 months (range: 4–100). The 2‐year‐OS was 84.1% for the entire cohort. High PD‐1 and PD‐L1 expression were more common in patients with positive HPV16 DNA (p < 0.001 and p = 0.008, respectively) and high infiltration by CD8+ TILs (p < 0.001 for both markers). High PD‐L1 expression correlated with superior OS (p = 0.025), LPFS (p = 0.047) and DMFS (p = 0.048) in multivariable analysis, whereas no significance could be demonstrated for PD‐1. Patients with CD8^high/PD‐L1^high expression had favorable outcome (p < 0.001 for all endpoints) compared to other groups. We validated the superior OS data on CD8^high/PD‐L1^high using the Cancer Genome Atlas TCGA dataset (n = 518; p = 0.032). High PD‐L1 expression was a favorable prognostic marker in HPV16‐negative but not HPV16‐positive patients. In conclusion, HPV‐positive tumors showed higher expression of immune markers. PD‐L1 expression constitutes an independent prognostic marker in SCCHN patients post‐adjuvant CRT. In conjunction with CD8 status, these data provide an important insight on the immune contexture of SCCHN and are directly relevant for future treatment stratification with PD‐1/PD‐L1 immune checkpoint inhibitors to complement CRT.     

Geographic heterogeneity in the prevalence of human papillomavirus in head and neck cancer

Human papillomavirus (HPV) causes oropharyngeal squamous cell carcinoma (OPSCC), although strongly divergent results have been reported regarding the prevalence of HPV16 in different countries, whether this represents important differences in etiology remains unclear. Applying rigorous protocols for sample processing, we centrally evaluated 1,420 head and neck tumors (533 oropharynx, 395 oral cavity and 482 larynx) from studies conducted in the US, Europe and Brazil for mucosal HPV DNA and p16^INK4a expression to evaluate regional heterogeneity in the proportion of HPV16‐associated OPSCC and other head and neck cancer, and to assess covariates associated with the risk of HPV16‐positive OPSCC. While majority of OPSCC in the US (60%) were HPV16‐positive, this proportion was 31% in Europe and only 4% in Brazil (p < 0.01). Similar differences were observed for other head and neck tumors, ranging from 7% in the US and 5% in Europe, to 0% in South America. The odds of HPV16‐positive OPSCC declined with increasing pack years of smoking (OR: 0.75; 95% CI: 0.64–0.87) and drink years of alcohol use (OR: 0.64; 95% CI: 0.54–0.76). These results suggest that while the contribution of HPV16 is substantial for the oropharynx, it remains limited for oral cavity and laryngeal cancers.     

CD8‐alpha T‐cell infiltration in human papillomavirus‐related oropharyngeal carcinoma correlates with improved patient prognosis

Patients with human papillomavirus (HPV)‐related oropharyngeal tumors display improved prognosis. The biological basis of this tumor phenotype is poorly understood. We investigated whether increased lymphocyte infiltrate in HPV‐positive oropharyngeal squamous cell carcinomas could account for better prognosis. We previously identified, in an Affymetrix GeneChip analysis of 83 HPV‐unrelated and 11 HPV‐related squamous cell carcinoma of the oropharynx, several candidate genes, including CD8α and CD3ζ. Their expression was validated in this study by qRT–PCR on an independent clinical series of 144 oropharyngeal tumors. Immunohistochemical staining of tumor specimens was performed to evaluate infiltration of tumor stroma by CD8+ and CD4+ lymphocytes. The prognostic value of CD8α and CD3ζ expression levels was measured by Kaplan–Meier and Cox regression model analyses. Immune response‐related signaling pathways were found to be deregulated in HPV‐positive oropharyngeal tumors. Expression of CD8α, CD3ζ, granzyme K, CD28 and integrin αL RNAs was upregulated in HPV‐positive lesions when compared with HPV‐unrelated tumors (p < 0.05). Stroma of HPV‐positive tumors was frequently and strongly infiltrated by CD8α‐ and CD3ζ‐positive T cells. CD8α RNA expression correlated with both improved global (Kaplan–Meier; p = 0.005; Cox regression: p = 0.003) and disease‐free (Cox regression: p = 0.04) survival. CD3ζ RNA expression correlated with improved overall survival (Cox regression: p = 0.024). These results suggest that an increased cytotoxic T‐cell‐based antitumor immune response is involved in improved prognosis of patients with HPV‐positive tumors.     

The role of postoperative chemoradiation for oropharynx carcinoma: A critical appraisal of the published literature and National Comprehensive Cancer Network guidelines

The National Comprehensive Cancer Network (NCCN) describes the presence of extracapsular spread and/or positive margins in oropharynx cancer (OPC) as an indication for the addition of chemotherapy to postoperative radiation. The guideline's category 1 consensus is based on what they term high‐level evidence. For this study, the authors performed a critical appraisal of the research upon which the NCCN guideline is based and assessed its relevance in the era of human papillomavirus (HPV)/p16‐positive OPC. Multiple shortcomings were identified, including patient exclusion after randomization and the use of unplanned subgroup analyses without multivariate adjustment, which undermined internal validity. Indeterminate HPV/p16 status limited external validity. Given the unique biology of HPV/p16‐positive tumors and the problems of internal and external validity, the authors concluded that the literature upon which the recommendation for the addition of chemotherapy to adjuvant radiation was based does not generate high‐level evidence, and its relevance for the postoperative management of patients with HPV/p16‐positive OPC remains unknown. Cancer 2015;121:1747–1754. © 2015 American Cancer Society.     

Epidemiologic associations of HPV‐positive oropharyngeal cancer and (pre)cancerous cervical lesions

Human papillomavirus (HPV)‐induced oropharyngeal squamous cell carcinoma (OPSCC) remains increasing worldwide. We aimed to investigate if the HPV‐prevalence of OPSCC in the Netherlands is rising as well, also in female patients. In addition, we evaluated the association between HPV‐positive OPSCC and suspicious Pap results of the cervix in these female patients. Patients with OPSCC treated in the period 2000–2015 at the VU University Medical Center Amsterdam, were included (n = 926). The presence of an oncogenic HPV infection was determined by p16‐immunostaining, followed by a high‐risk HPV general primer 5+/6+ DNA PCR on the p16‐immunopositive cases. A review of pathology reports in all female patients (n = 305) was undertaken to identify cytological signs of HPV‐related (pre)cancer of the cervix. In total 281 of 926 (30.3%) OPSCCs were HPV‐positive. Moreover, a significant increase in the prevalence of HPV‐positive OPSCCs was observed from 14.0% in 2000 to 48.1% in 2015 (p < 0.001). Among the female patients with an HPV‐positive OPSSC (n = 70), the results of cervical smears were available in 56 of 70 patients (80.0%). Of the female patients with HPV‐positive OPSCC, 9 of 56 (16.1%) patients had a vaginal cuff Papanicolaou (Pap) test ≥3b in their medical history compared to 7 of 168 (4.2%) in the HPV‐negative group (p = 0.003). In conclusion, a continuous increase in the HPV‐attributable fraction of OPSCC was demonstrated in the period 2000–2015 in the Amsterdam region. HPV‐positive OPSCC has a significant association with a history of suspicious Pap results of the cervix in female patients.     

Racial differences in breast cancer survival in the Detroit Metropolitan area

Summary African American (AA) women have poorer breast cancer survival compared to Caucasian American (CA) women. The purpose of this analysis was to determine whether socioeconomic status (SES) and treatment differences influence racial differences in breast cancer survival. The study population included 9,321 women (82% CA, 18% AA) diagnosed with local (63%) or regional (37%) stage disease between 1988 and 1992, identified through the Metropolitan Detroit SEER registry. Data on SES were obtained through linkage with the 1990 Census of Population and Housing Summary Tape and cases were geocoded to census block groups. Pathology, treatment and survival data were obtained through SEER. Cox proportional hazards models were used to compare survival for AA versus CA women after adjusting for age, SES, tumor size, number of involved lymph nodes, and treatment. AA␣women were more likely to live in a geographic area classified as working poor than were CA women (p<0.001). AA women were less likely to have lumpectomy and radiation and more likely to have mastectomy with radiation (p<0.001). After multivariable adjusted analysis, there were no significant racial differences in survival among women with local stage disease, although AA women with regional stage disease had persistent but attenuated poorer survival compared to CA women. After adjusting for known clinical and SES predictors of survival, AA and CA women who are diagnosed with local disease demonstrate similar overall and breast cancer-specific survival, while race continues to have an independent effect among women presenting at a later stage of disease.     

Investigating the health disparities in the association between lifestyle behaviors and the risk of head and neck cancer

Many studies have reported a positive association between lower socioeconomic status (SES) and higher head and neck cancer (HNC) risk. Fewer studies have examined the impact of SES on the association between alcohol or cigarette use and HNC risk. The current case‐control study (1104 HNC cases and 1363 controls) investigated the influence of education, a SES indicator, on the association between HNC and the use of alcohol, cigarettes, or betel quids in Taiwan, a country with universal health care. Our results showed a larger increase in HNC risk associated with alcohol among those with lower educational level (odds ratio [OR] = 2.07; 95% confidence interval [CI], 1.53‐2.80) than those with higher educational level (OR = 1.38; 95% CI, 1.04‐1.85) (heterogeneity‐P = .03). Educational level had an influence on the association between alcohol use and HNC risk among those with genetic susceptibility (ALDH2‐deficient) to the carcinogenic effect of alcohol. The association between cigarette or betel quid use and HNC risk was similar between the high and low educational groups. National policies and social interventions have led to the decline in the prevalence of cigarette and betel quid users in Taiwan. In contrast, due to the lack of adequate alcohol control policies, alcohol consumption in Taiwan has continued to rise. A higher impact of alcohol on HNC risk among lower SES individuals even with universal health care could be the result of insufficient alcohol control policies in Taiwan.     

Racial differences in colorectal cancer survival in the Detroit Metropolitan area

BACKGROUND:

Colorectal carcinoma is the second most common cause of cancer death with African Americans having lower survival compared with White Americans. The purpose of this study was to investigate the effect of demographics, clinical factors, and socioeconomic status (SES) on racial disparities in colorectal cancer survival in the Detroit Metropolitan Area.

METHODS:

The study population included 9078 individuals with primary invasive colorectal cancer identified between 1988 and 1992 through the Surveillance, Epidemiology, and End Results (SEER) program. Demographics, clinical information, and survival were obtained through SEER. SES was categorized using occupation, educational level, and poverty status at the census tract level. Kaplan‐Meier survival curves and Cox proportional hazards regression were used to compare overall survival by race.

RESULTS:

African Americans were more likely to be diagnosed with stage IV disease (P < .001), and to reside within poor census tracts (P < .001) compared with White Americans. Unadjusted analysis showed that African Americans had a significantly higher risk of death compared with their White American counterparts (hazards ratio [HR], 1.13; 95% confidence interval [CI], 1.07‐1.20). After adjusting for age, marital status, sex, SES group, TNM stage, and treatment, race was no longer significantly associated with overall survival (HR, 1.00; 95% CI, 0.92‐1.09). Similar results were seen with colorectal cancer‐specific survival.

CONCLUSIONS:

Racial disparities in colorectal cancer survival dissipate after adjusting for other demographic and clinical factors. These results can potentially affect medical guidelines regarding screening and treatment, and possibly influence public health policies that can have a positive impact on equalizing racial differences in access to care. Cancer 2009. © 2009 American Cancer Society.     

Novel biomarker panel predicts prognosis in human papillomavirus-negative oropharyngeal cancer: an analysis of the TAX 324 trial

BACKGROUND:

New treatment strategies for locally advanced head and neck squamous cell carcinoma combine induction chemotherapy and chemoradiation. Identifying the predictors of outcome in sequentially treated patients is critical for focusing therapeutic research. In this analysis, the authors evaluated human papillomavirus type 16 (HPV‐16) status and the expression levels of a defined set of biomarkers to identify predictors of response to this treatment modality.

METHODS:

In total, 114 patients with oropharyngeal cancer (OPC) who were treated on the TAX 324 trial (cisplatin and fluorouracil with or without docetaxel in patients with locally advanced head and neck squamous cell carcinoma) had pretreatment biopsy specimens that were evaluable for HPV‐16 DNA and immunohistochemical expression of the following biomarkers: beta‐tubulin II (βT‐II), glutathione S‐transferase (GST‐π), p53, and B‐cell lymphoma 2 (Bcl‐2). Patients were categorized into risk groups based on their HPV status and biomarker expression levels.

RESULTS:

Patients with high‐risk OPC were defined by HPV‐negative status and either elevated expression of βT‐II or levels of at least 2 of the other 3 adverse markers (elevated GST‐π, elevated p53, or low Bcl‐2). All other HPV‐negative patients were categorized as moderate risk. In total, 55 patients were HPV‐positive, and 59 patients were HPV‐negative, with 34 were categorized as high risk and 25 categorized as moderate risk. The median survival for HPV‐positive patients was not reached. The median survival was 44.2 months for moderate‐risk patients (95% confidence interval, 20.9 months to not reached) and 12.1 months for high‐risk patients (95% confidence interval, 7.5‐19.7 months). The 24‐month survival rate was 89% for HPV‐positive patients, 67% for moderate‐risk patients, and 29% for high‐risk patients (P < .0001).

CONCLUSIONS:

The molecular data set in this study readily differentiated between 2 distinct groups of patients with locally advanced, HPV‐negative OPC. This risk‐stratification strategy may serve as a guide for treatment selection. Cancer 2012;. © 2011 American Cancer Society.     

Diagnostic accuracy of HPV16 early antigen serology for HPV-driven oropharyngeal cancer is independent of age and sex

A growing proportion of head and neck cancer (HNC), especially oropharyngeal cancer (OPC), is caused by human papillomavirus (HPV). There are several markers for HPV-driven HNC, one being HPV early antigen serology. We aimed to investigate the diagnostic accuracy of HPV serology and its performance across patient characteristics. Data from the VOYAGER consortium was used, which comprises five studies on HNC from North America and Europe. Diagnostic accuracy, that is, sensitivity, specificity, Cohen's kappa and correctly classified proportions of HPV16 E6 serology, was assessed for OPC and other HNC using p16^INK4a immunohistochemistry (p16), HPV in situ hybridization (ISH) and HPV PCR as reference methods. Stratified analyses were performed for variables including age, sex, smoking and alcohol use, to test the robustness of diagnostic accuracy. A risk-factor analysis based on serology was conducted, comparing HPV-driven to non-HPV-driven OPC. Overall, HPV serology had a sensitivity of 86.8% (95% CI 85.1-88.3) and specificity of 91.2% (95% CI 88.6-93.4) for HPV-driven OPC using p16 as a reference method. In stratified analyses, diagnostic accuracy remained consistent across sex and different age groups. Sensitivity was lower for heavy smokers (77.7%), OPC without lymph node involvement (74.4%) and the ARCAGE study (66.7%), while specificity decreased for cases with <10 pack-years (72.1%). The risk-factor model included study, year of diagnosis, age, sex, BMI, alcohol use, pack-years, TNM-T and TNM-N stage. HPV serology is a robust biomarker for HPV-driven OPC, and its diagnostic accuracy is independent of age and sex. Future research is suggested on the influence of smoking on HPV antibody levels.     

Racial disparities and socioeconomic status in men diagnosed with testicular germ cell tumors: a survival analysis

BACKGROUND:

Previous reports indicated that African‐American men with testicular germ cell tumors (TGCTs) have more aggressive tumor characteristics and less favorable outcomes than other men. The authors of this report evaluated the effects of race and socioeconomic status (SES) on stage distribution, overall mortality (OM), and cancer‐specific mortality (CSM) in men with TGCTs.

METHODS:

The Surveillance, Epidemiology, and End Results (SEER) database was used to identify 22,553 men who were diagnosed with TGCTs between 1988 and 2006. Kaplan‐Meier and Cox regression analyses were generated to predict OM and CSM. Covariates of the analyses included race, SES, age, histologic subtype, disease stage, procedure type, SEER registry, and year of diagnosis. The interaction between race and SES also was examined.

RESULTS:

Overall, there were 516 African‐American men, 21,090 Caucasian men, and 947 men of other races. African‐Americans (14.9%) and individuals with low SES (10.7%) had a higher proportion of distant stage disease. CSM and OM rates were significantly higher for African‐American patients and for patients who resided in low SES counties. Multivariate analyses revealed that African‐American men and men with low SES were more likely to die of OM and CSM relative to Caucasian men (P < .001) and men with high SES (P < .001), respectively. The interaction between race and SES was not significant.

CONCLUSIONS:

African‐American race and low SES appeared to predispose men to more advanced disease stages and to higher OM and CSM rates. These observations may warrant race‐specific and/or SES‐specific adjustments in the treatment of TGCT. Cancer 2011;. © 2011 American Cancer Society.