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.

A Single Institution Retrospective Comparison Study of Locoregional Recurrence After Accelerated Partial Breast Irradiation Using External Beam Fractionation Compared with Whole Breast Irradiation with 8 Years of Follow-Up.

BACKGROUND: Accelerated partial breast irradiation (APBI) was developed to address disadvantages of overall treatment time and potentially unnecessary radiation associated with whole breast irradiation (WBI). We report updated results of our single institution study using an external beam APBI regimen with a median follow-up of 8 years. METHODS: A total of 290 APBI patients with AJCC Stage 0-II breast cancer were compared with 290 WBI patients with matched tumor characteristics. Toxicities were scored based on the Common Terminology Criteria for Adverse Events (CTCAE v3.0). Cox regression models were used to predict likelihood of freedom from ipsilateral failure. RESULTS: Median follow-up was 8 years in the APBI group and 7.5 years in the WBI group. In the APBI group, there were 18 (6.2%) ipsilateral breast tumor recurrence (IBTR), 13 (72%) had elsewhere failures (EF), and 5 (28%) had local failures (LF) with a median time to failure of 64.1 months. In the WBI group, there were three (1.0%) IBTR; one (33%) was an EF and two (67%) were LF with a median time to failure of 91 months. APBI was 4.6 times more likely (hazard ratio 4.57, 95% confidence interval 1.3-16.2, p = 0.02) to have an IBTR than WBI after adjusting for age, tumor size, histology, grade, and estrogen receptor status. Fatigue, erythema, and desquamation toxicities were significantly less in the APBI group then the WBI group. CONCLUSIONS: IBTR rates were higher in external beam APBI group compared with WBI, but APBI had fewer toxicities. Clinicians must weigh the risks and benefits of APBI when making a recommendation for partial breast irradiation after lumpectomy.

Clinical accuracy of preoperative breast MRI for breast cancer.

BACKGROUND: It is unclear if breast magnetic resonance imaging (MRI) is more accurate than mammography (MGM) and ultrasound (U/S) in aggregate for patients with invasive cancer. METHODS: We compared concordance of combined tumor size and tumor foci between MRI and MGM and U/S combined to pathological tumor size and foci as the gold standard from 2009 to 2015. Tumor size was nonconcordant if it differed from the pathologic size by ≥33% and tumor foci was nonconcordant if >1 foci were seen. If one or both of the MGM or U/S was nonconcordant and the MRI was concordant, MRI provided greater accuracy. RESULTS: Of 471 patients with MGM, US, and MRI, MRI was more accurate for 32.9% of patients for tumor size and for 21.9% for tumor foci. Patients for whom MRI had greater accuracy were compared to those who did not for clinical and tumor factors. The only significant factor was calcifications on mammography. Tumor size, stage, molecular subtype, histology, grade, patient BMI, age, mammographic density, and use of hormone replacement therapy were not significantly different. CONCLUSIONS: Breast MRI provides greater accuracy for a third of patients undergoing preoperative MGM and U/S. Mammographic calcifications were associated with MRI clinical accuracy for patients with invasive cancer.

Trends and variation in the use of nipple-sparing mastectomy for breast cancer in the United States.

PURPOSE: For many women, nipple-sparing mastectomy (NSM) provides aesthetic and quality-of-life outcomes superior to skin-sparing mastectomy. Accumulating data suggest that NSM provides similar oncologic outcomes in select breast cancer patients. This study sought to determine national trends in NSM use. METHODS: Using the National Cancer Data Base, 6254 women with breast cancer who underwent NSM between 2010 and 2013 were identified. NSM rates were determined relative to the number of patients who received a mastectomy with reconstruction (n = 114,849). Associations between patient, tumor, and facility characteristics and NSM were assessed using logistic regression. RESULTS: The rate of NSM increased from 2.9 to 8.0 % between 2010 and 2013. NSM was most commonly performed in academic (adjusted odds ratio [OR] 1.43, p < 0.001) and high-volume (OR 1.59, p < 0.001) breast centers. There was up to a 5.8-fold variation in its delivery between geographic census regions (p < 0.001). Of 1231 hospitals, only 491 (39.9 %) reported performing at least one NSM during the study period. Half of all NSMs were performed by the top 6 % (n = 30) of NSM-performing centers. NSM was associated with small tumor size (p < 0.001), lower tumor grades (p < 0.05), and negative nodal status (p < 0.001). However, half of NSM patients had at least one tumor characteristic that diverged from current (2016) NCCN recommendations for the procedure. CONCLUSIONS: The use of therapeutic NSM is increasing dramatically in the United States, despite recommendations that the procedure be used with caution. As NSM becomes increasingly common, efforts are needed to monitor its long-term oncologic outcomes and to ensure equitable access to it.

Utilization of Axillary Surgery for Patients With Ductal Carcinoma In Situ: A Report From the National Cancer Data Base.

BACKGROUND: This study evaluated the use of axillary surgery (AS), including sentinel lymph node biopsy (SLNB), for patients with ductal carcinoma in situ (DCIS) and the factors associated with its use. To determine whether utilization of SLNB is appropriate, predictors of SLNB performance were compared with factors predictive of tumor upstaging. METHODS: The National Cancer Data Base was utilized to identify patients with American Joint Committee on Cancer (AJCC) clinical stage 0 breast cancer treated from 2004 to 2013. DCIS with microinvasion was excluded. Chi square tests and logistic regression were used to examine patient, tumor, and facility features associated with SLNB and tumor upstaging. RESULTS: Of the 218,945 total patients, 155,093 (70.8 %) underwent lumpectomy, and 63,852 (29.2 %) underwent mastectomy. SLNB was performed for 19.0 % of lumpectomy patients and 63.5 % of mastectomy patients. Multivariate analysis for 2012-2013 demonstrated that estrogen receptor (ER)-negative and grade 3 tumors were more likely to be treated with SLNB in both groups. Tumor size was significant only for the lumpectomy patients who underwent one operation. Further, 22.8 % of lumpectomy patients and 18.7 % of mastectomy patients who underwent AS were upstaged compared with 1.8 % of lumpectomy and 3.6 % of mastectomy patients who did not undergo AS. Tumor upstaging was predicted by ER-negative status (odds ratio [OR] 2.99; 95 % confidence interval [CI] 2.76-3.24) but not by higher grade or larger tumor size. CONCLUSIONS: Use of SLNB for DCIS is high with mastectomy, and nearly one fifth of the lumpectomy patients underwent SLNB. However, the performance of AS was strongly associated with the likelihood of upstaging in both groups, suggesting that surgical judgment plays an important role in this decision.

The Presence of Phage Orthologous Genes in Helicobacter pylori Correlates with the Presence of the Virulence Factors CagA and VacA.

BACKGROUND: The bacterium Helicobacter pylori is associated with ulcers and the development of gastric cancer. Several genes, including cytotoxin-associated gene A (CagA) and vacuolating cytotoxin A (VacA), are associated with increased gastric cancer risk. Some strains of H. pylori also contain sequences related to bacteriophage phiHP33; however, the significance of these phage-related sequences remains unknown. MATERIALS AND METHODS: We assessed the extent to which phiHP33-related sequences are present in 335 H. pylori strains using homology searches then mapped shared genes between phiHP33 and H. pylori strains onto an existing phylogeny. RESULTS: One hundred and twenty-one H. pylori strains contain phage orthologous sequences, and the presence of the phage-related sequences correlates with the presence of CagA and VacA. Mapping of the phage orthologs onto a phylogeny of H. pylori is consistent with the hypothesis that these genes were acquired by horizontal gene transfer. CONCLUSIONS: phiHP33 phage orthologous sequences might be of significance in understanding virulence of different H. pylori strains.

Synchronous Leydig Cell Tumor and Seminoma in the Ipsilateral Testis.

Leydig cell tumor is a rare sex cord tumor that accounts for 1-3% of all testicular neoplasms. Seminomas are more common and occur in 30-40% of testicular tumors. Leydig cell tumors are derived from undifferentiated gonadal mesenchyme and the concurrent development of the tumor and a seminoma which are derived from germinal epithelium in an ipsilateral testis is extremely rare. Here we report a case of ipsilateral Leydig cell tumor and seminoma occurring in a 38-year-old man with a left testicular mass. The key to diagnosis is dependent on histopathology and immunohistochemistry. To our knowledge, this is the first diagnosis of the two disease entities in a unilateral testis using immunohistochemistry. Increased awareness of the entity is important in order to distinguish Leydig cell tumor and seminomas from other malignancies due to difference in therapeutic management.

Risk of Development of Second Primary Head and Neck Cancer following an Index Breast Cancer.

Objective Many head and neck cancers (HNCs) have genomic features seen in breast malignancy. We sought to analyze the risk of second primary HNC following an index breast cancer. Study Design Retrospective cohort study. Setting National database from the SEER registry (Surveillance, Epidemiology, and End Results). Subjects and Methods Within the SEER database, 223,423 women diagnosed with index breast cancer from 1992 to 2002 were identified. We calculated standard incidence ratios (SIRs) for all head and neck sites with 10-year follow-up. Results Women diagnosed with an index breast cancer did not exhibit higher likelihood of developing second primary HNC (SIR = 0.99; 95% CI, 0.90-1.07). The risk was determined for each subsite of the head and neck, and salivary gland cancer presented the highest risk. Patients with index breast cancer were 83% more likely to develop salivary gland cancer than what would be expected in the general population (SIR = 1.83; 95% CI, 1.49-2.22). An overall trend of increased risk was observed for salivary gland cancers between 1992 and 2002. There was no significant higher risk observed for the other head and neck subsites. Conclusion Patients with index breast cancer did not have a higher-than-expected risk of developing HNC. We did find an increased incidence of salivary gland cancers among patients with index breast cancer. Patients were 80% more likely to develop salivary gland cancer than that expected within the population. These findings warrant further investigation on the relationship between salivary gland and breast malignancy.

Racial disparities in the choice of definitive treatment for squamous cell carcinoma of the oral cavity.

BACKGROUND: Definitive surgery is recommended for oral cavity squamous cell carcinoma (SCC). The purpose of this study was to present our assessment of the disparities in treatment selection for oral cavity SCC. METHODS: Non-Hispanic white and non-Hispanic black patients with oral cavity SCC were identified in the National Cancer Database (NCDB). Regression models were used to estimate relative risk (RR) of receiving surgery and absolute difference between non-Hispanic white and non-Hispanic black patients. RESULTS: There were 82.3% of non-Hispanic white patients who received surgery, compared to 64.2% of non-Hispanic black patients (P < .001). The non-Hispanic black patients were less likely to receive surgery than non-Hispanic white patients (RR 0.87) with an absolute difference of 10.9%. The non-Hispanic black patients were significantly more likely to not be offered surgery (RR 1.42) and to refuse recommended surgery (RR 1.38) but not have a contraindication to surgery (RR 1.17). CONCLUSION: The non-Hispanic black patients are less likely to receive or be recommended surgery for oral cavity SCC and are more likely to refuse surgery. Further study is needed to identify strategies to close this disparity.

Evidence for horizontal gene transfer between Chlamydophila pneumoniae and Chlamydia phage.

Chlamydia-infecting bacteriophages, members of the Microviridae family, specifically the Gokushovirinae subfamily, are small (4.5-5 kb) single-stranded circles with 8-10 open-reading frames similar to E. coli phage ϕX174. Using sequence information found in GenBank, we examined related genes in Chlamydophila pneumoniae and Chlamydia-infecting bacteriophages. The 5 completely sequenced C. pneumoniae strains contain a gene orthologous to a phage gene annotated as the putative replication initiation protein (PRIP, also called VP4), which is not found in any other members of the Chlamydiaceae family sequenced to date. The C. pneumoniae strain infecting koalas, LPCoLN, in addition contains another region orthologous to phage sequences derived from the minor capsid protein gene, VP3. Phylogenetically, the phage PRIP sequences are more diverse than the bacterial PRIP sequences; nevertheless, the bacterial sequences and the phage sequences each cluster together in their own clade. Finally, we found evidence for another Microviridae phage-related gene, the major capsid protein gene, VP1 in a number of other bacterial species and 2 eukaryotes, the woodland strawberry and a nematode. Thus, we find considerable evidence for DNA sequences related to genes found in bacteriophages of the Microviridae family not only in a variety of prokaryotic but also eukaryotic species.