A New Tool Improves Diagnostic Test Performance for Transmission EM Evaluation of Axonemal Dynein Arms

Diagnosis of primary ciliary dyskinesia (PCD) by identification of dynein arm loss in transmission electron microscopy (TEM) images can be confounded by high background noise due to random electron-dense material within the ciliary matrix, leading to diagnostic uncertainty even for experienced morphologists. We developed a novel image analysis tool to average the axonemal peripheral microtubular doublets, thereby increasing microtubular signal and reducing random background noise. In a randomized, double-blinded study that compared two experienced morphologists and three different diagnostic approaches, we found that use of this tool led to improvement in diagnostic TEM test performance

Body mass index and risk of head and neck cancer by race: the Carolina Head and Neck Cancer Epidemiology Study

Most studies, primarily conducted in populations of European ancestry, reported increased risk of head and neck cancer (HNC) associated with leanness (body mass index (BMI) 30 kg/m2, respectively), compared to normal weight (18.5-<25.0 kg/m2)

Racial differences in the relationship between tobacco, alcohol, and squamous cell carcinoma of the head and neck

Tobacco and alcohol use are well-known risk factors for squamous cell carcinoma of the head and neck (SCCHN), but there has been little examination of disparities in SCCHN and racial patterns of tobacco and alcohol use, especially for African-Americans. The Carolina Head and Neck Cancer Study, a population-based case-control study, was utilized to determine if relationships between tobacco and alcohol use and SCCHN differed by race

Human papillomavirus in head and neck squamous cell carcinoma: A descriptive study of histologically confirmed cases at Kamuzu Central Hospital in Lilongwe, Malawi

Background: Head and neck squamous cell carcinoma (HNSCC) is common in sub-Saharan Africa, but the aetiologic contribution of human papillomavirus (HPV) is not well established.Methods: We assessed HNSCC cases for HPV using p16 immunohistochemistry (IHC) in Malawi. Associations between p16 IHC and tumour site, behavioural risk factors, demographic characteristics, and HIV status were examined.Results: From 2010 to 2014, 77 HNSCC cases were identified. Mean age was 52 years, 50 cases (65%) were male, and 48 (62%) were in the oropharynx (OP) or oral cavity (OC). HIV status was known for 35 patients (45%), with 5 (14%) HIV-infected. Substance use was known for 40 patients (52%), with 38% reporting any tobacco and 31% any alcohol. Forty-two cases (55%) had adequate tissue for p16 IHC, of which seven (17%) were positive, including 22% of OP/OC tumours.Conclusions: Despite high cervical cancer burden, HPV-associated HNSCC is not very common in Malaw

Associations Between Dietary Patterns and Head and Neck Cancer: The Carolina Head and Neck Cancer Epidemiology Study

Few studies have examined the associations between dietary patterns and head and neck squamous cell carcinoma (SCC) or whether they differ by race. This was evaluated using data from a population-based case-control study (2002–2006) including 1,176 cases of head and neck SCC and 1,317 age-, race-, and gender-matched controls from central and eastern North Carolina whose diets had been assessed by food frequency questionnaire. Factor analysis identified 2 patterns of intake: 1) high consumption of fruits, vegetables, and lean protein and 2) high consumption of fried foods, high-fat and processed meats, and sweets. Associations were estimated using logistic regression, adjusting for matching factors and confounders. Heterogeneity by tumor site (oral/pharyngeal vs. laryngeal) and effect-measure modification were also evaluated. Reduced odds of head and neck SCC were found for the fruit, vegetable, and lean protein pattern (for highest quartile vs. lowest, odds ratio = 0.53, 95% confidence interval: 0.39, 0.71). The fried foods, high-fat and processed meats, and sweets pattern was positively associated only with laryngeal cancer (odds ratio = 2.12, 95% confidence interval: 1.21, 3.72). These findings underline the importance of a dietary pattern rich in fruits and vegetables and low in high-fat and processed meats and sweets for prevention of head and neck cancer

Oral health and risk for head and neck squamous cell carcinoma: the Carolina Head and Neck Cancer Study

Recent reports have linked oral health and periodontal disease indicators with increased risk of squamous cell carcinoma of head and neck (SCCHN). Thus far, evidence has been inconclusive; our objective was to study the association between oral health and SCCHN risk in the context of a large population-based study

Malaria, Intestinal Helminths and Other Risk Factors for Stillbirth in Ghana

Objective. The objective of the study was to assess Plasmodium/intestinal helminth infection in pregnancy and other risk factors for stillbirth in Ghana. Methods. A cross-sectional study of women presenting for delivery in two hospitals was conducted during November-December 2006. Data collected included sociodemographic information, medical and obstetric histories, and anthropometric measures. Laboratory investigations for the presence of Plasmodium falciparum and intestinal helminths, and tests for hemoglobin levels were also performed. Results. The stillbirth rate was relatively high in this population (5%). Most of the stillbirths were fresh and 24% were macerated. When compared to women with no malaria, women with malaria had increased risk of stillbirth (OR = 1.9, 95% CI = 1.2–9.3). Other factors associated with stillbirth were severe anemia, low serum folate concentration, past induced abortion, and history of stillbirth. Conclusion. The fact that most of the stillbirths were fresh suggests that higher quality intrapartum care could reduce stillbirth rates

Relevance, Pathogenesis, and Testing Algorithm for Mismatch Repair–Defective Colorectal Carcinomas

Loss-of-function defects in DNA mismatch repair (MMR), which manifest as high levels of microsatellite instability (MSI), occur in approximately 15% of all colorectal carcinomas (CRCs). This molecular subset of CRC characterizes patients with better stage-specific prognoses who experience no benefit from 5-fluorouracil chemotherapy. Most MMR-deficient (dMMR) CRCs are sporadic, but 15% to 20% are due to inherited predisposition (Lynch syndrome). High penetrance of CRCs in germline MMR gene mutation carriers emphasizes the importance of accurate diagnosis of Lynch syndrome carriers. Family-based (Amsterdam), patient/family-based (Bethesda), morphology-based, microsatellite-based, and IHC-based screening criteria do not individually detect all germline mutation carriers. These limitations support the use of multiple concurrent tests and the screening of all patients with newly diagnosed CRC. This approach is resource intensive but would increase detection of inherited and de novo germline mutations to guide family screening. Although CRC prognosis and prediction of 5-fluorouracil response are similar in both the Lynch and sporadic dMMR subgroups, these subgroups differ significantly with regard to the implications for family members. We recommend that new CRCs should be classified into sporadic MMR-proficient, sporadic dMMR, or Lynch dMMR subgroups. The concurrent use of MSI testing, MMR protein IHC, and BRAF c.1799T>A mutation analysis would detect almost all dMMR CRCs, would classify 94% of all new CRCs into these MMR subgroups, and would guide secondary molecular testing of the remainder

Relevance, Pathogenesis, and Testing Algorithm for Mismatch Repair–Defective Colorectal Carcinomas A Report of the Association for Molecular Pathology

Loss-of-function defects in DNA mismatch repair (MMR), which manifest as high levels of microsatellite instability (MSI), occur in approximately 15% of all colorectal carcinomas (CRCs). This molecular subset of CRC characterizes patients with better stage-specific prognoses who experience no benefit from 5-fluorouracil chemotherapy. Most MMR-deficient (dMMR) CRCs are sporadic, but 15% to 20% are due to inherited predisposition (Lynch syndrome). High penetrance of CRCs in germline MMR gene mutation carriers emphasizes the importance of accurate diagnosis of Lynch syndrome carriers. Family-based (Amsterdam), patient/family-based (Bethesda), morphology-based, microsatellite-based, and IHC-based screening criteria do not individually detect all germline mutation carriers. These limitations support the use of multiple concurrent tests and the screening of all patients with newly diagnosed CRC. This approach is resource intensive but would increase detection of inherited and de novo germline mutations to guide family screening. Although CRC prognosis and prediction of 5-fluorouracil response are similar in both the Lynch and sporadic dMMR subgroups, these subgroups differ significantly with regard to the implications for family members. We recommend that new CRCs should be classified into sporadic MMR-proficient, sporadic dMMR, or Lynch dMMR subgroups. The concurrent use of MSI testing, MMR protein IHC, and BRAF c.1799T>A mutation analysis would detect almost all dMMR CRCs, would classify 94% of all new CRCs into these MMR subgroups, and would guide secondary molecular testing of the remainder

Single-Nucleotide Polymorphisms in Nucleotide Excision Repair Genes, Cigarette Smoking, and the Risk of Head and Neck Cancer

Cigarette smoking is associated with increased head and neck cancer (HNC) risk. Tobacco-related carcinogens are known to cause bulky DNA adducts. Nucleotide excision repair (NER) genes encode enzymes that remove adducts and may be independently associated with HNC, as well as modifiers of the association between smoking and HNC