Paul Brennan and colleagues perform genome-wide association analysis for oral cavity and pharyngeal cancer in trans-ancestry populations. They find seven new loci across different cancer subtypes, including a protective association in the HLA region that has a stronger effect in patients with human papillomavirus–positive cancers. We conducted a genome-wide association study of oral cavity and pharyngeal cancer in 6,034 cases and 6,585 controls from Europe, North America and South America. We detected eight significantly associated loci (P < 5 × 10−8), seven of which are new for these cancer sites. Oral and pharyngeal cancers combined were associated with loci at 6p21.32 (rs3828805, HLA-DQB1), 10q26.13 (rs201982221, LHPP) and 11p15.4 (rs1453414, OR52N2–TRIM5). Oral cancer was associated with two new regions, 2p23.3 (rs6547741, GPN1) and 9q34.12 (rs928674, LAMC3), and with known cancer-related loci—9p21.3 (rs8181047, CDKN2B-AS1) and 5p15.33 (rs10462706, CLPTM1L). Oropharyngeal cancer associations were limited to the human leukocyte antigen (HLA) region, and classical HLA allele imputation showed a protective association with the class II haplotype HLA-DRB1*1301–HLA-DQA1*0103–HLA-DQB1*0603 (odds ratio (OR) = 0.59, P = 2.7 × 10−9). Stratified analyses on a subgroup of oropharyngeal cases with information available on human papillomavirus (HPV) status indicated that this association was considerably stronger in HPV-positive (OR = 0.23, P = 1.6 × 10−6) than in HPV-negative (OR = 0.75, P = 0.16) cancers.

Most polarized epithelia constrain solute diffusion between luminal and interstitial compartments using tight junctions and generate mechanical strength using adherens junctions. These intercellular junctions are typically portrayed as incongruent macromolecular complexes with distinct protein components. Herein, we delineate the molecular composition and subdomain architecture of an intercellular junction between sensory and non-sensory cells of the inner ear. In this junction, claudins partition into claudin-14 and claudin-9/6 subdomains that are distinguishable by strand morphology, which contrasts with in vitro data that most claudins co-assemble into heteromeric strands. Surprisingly, canonical adherens junction proteins (p120ctn, α- and β-catenins) colocalize with the claudin-9/6 subdomain and recruit a dense cytoskeletal network. We also find that catenins colocalize with claudin-9 and claudin-6, but not claudin-14, in a heterologous system. Together, our data demonstrate that canonical tight junction and adherens junction proteins can be recruited to a single junction in which claudins partition into subdomains and form a novel hybrid tight junction with adherens junction organization.

Background: Herpesviruses may be related to the etiology of aggressive periodontitis (AgP) and chronic periodontitis (CP) by triggering periodontal destruction or by increasing the risk for bacterial infection. This case‐control study evaluated the presence of herpes simplex virus type I (HSV‐1), Epstein‐Barr virus type I (EBV‐1), human cytomegalovirus (HCMV), Aggregatibacter actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans), Porphyromonas gingivalis, Prevotella intermedia, and Tannerella forsythia (previously T. forsythensis) in patients with generalized AgP (AgP group), CP (CP group), or gingivitis (G group) and in healthy individuals (C group).Methods: Subgingival plaque samples were collected with paper points from 30 patients in each group. The nested polymerase chain reaction (PCR) method was used to detect HSV‐1, EBV‐1, and HCMV. Bacteria were identified by 16S rRNA‐based PCR.Results: HSV‐1, HCMV, and EBV‐1 were detected in 86.7%, 46.7%, and 33.3% of the AgP group, respectively; in 40.0%, 50.0%, and 46.7% of the CP group, respectively; in 53.3%, 40.0%, and 20.0% of the G group, respectively; and in 20.0%, 56.7%, and 0.0% of the C group, respectively. A. actinomycetemcomitans was detected significantly more often in the AgP group compared to the other groups (P <0.005). P. gingivalis and T. forsythia were identified more frequently in AgP and CP groups, and AgP, CP, and G groups had higher frequencies of P. intermedia compared to the C group.Conclusion: In Brazilian patients, HSV‐1 and EBV‐1, rather than HCMV, were more frequently associated with CP and AgP.