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The number of non-small-cell lung cancer (NSCLC) patients reported as infected with human papillomavirus (HPV) varies among countries and by race and geographical location. Furthermore, the relationship between HPV and the expressions of p53 and p16 remains unclear. A large cohort of NSCLC patients from Shanghai was studied. Paraffin sections from 128 cases of lung adenocarcinoma (ADC) and 134 cases of squamous cell carcinoma (SQC) were collected from the Shanghai Chest Hospital. Samples were analyzed by polymerase chain reaction (PCR) and reverse dot blot for detection of HPV DNA and by immunohistochemistry for detection of p53 and p16 expressions. The rate of HPV infection in SQC cases was significantly higher than in ADC cases (12.69 versus 3.91%). Females with SQC had a significantly higher rate of HPV infection compared to males with SQC (18.75 versus 7.14%, p = 0.044). HPV infection was correlated with gender and age in SQC but not with the degree of tumor differentiation, TNM stage, or smoking. Koilocytosis was significantly correlated to the tumor differentiation grade, regardless of age and TNM stage. The expressions of p53 and p16 were correlated with HPV infection and the tumor histological type but not with the degree of tumor differentiation, TNM stage, smoking, gender, or age. p53-positive expression was significantly higher in HPV-infected SQC cases than in those not infected with HPV. There was no statistically significant difference in the expression of p16 between the two groups. Data showed that HPV infection may be an important virulence factor in SQC, particularly in female patients. HPV infection appears to be involved in cancer progression in SQC by promoting the expression of p53; however, p16 cannot be used as a surrogate marker for HPV infection in SQC.

Esophageal squamous cell carcinoma (ESCC) is one of the most common types of tumors worldwide, particularly in China, and human papillomavirus (HPV) is thought to be a potential risk factor for this cancer. To determine whether this is true, we collected 177 formalin-fixed and paraffin-embedded ESCC samples from two hospitals. We screened for 23 different HPV genotypes using a human papillomavirus genotyping kit, which allowed us to amplify the L1 gene by polymerase chain reaction (PCR) and test for 23 HPV subtypes by reverse dot blot (RDB) on a single membrane. We also used immunohistochemistry (IHC) to detect the P16(INK4a) protein, the expression of which is linked to HPV E7 activity and which is used to diagnose cervical intraepithelial neoplasia. The genotyping results showed that only six samples were weakly positive for HPV: two for HPV16, two for HPV11 and two for HPV35, with no samples showing strong positive signals. The IHC results showed only five samples with diffuse positive staining, with the other samples being completely negative or having only focal positive signals, which were considered as negative. This study demonstrates that the HPV infection rate in ESCC samples is very low, suggesting that HPV is not the etiological cause of ESCC.

The relationships between the expression of cyclin B1, EBV-LMP1, P53 and P16(INK4A) in Chinese classical Hodgkin lymphoma are unknown and need exploring. Samples of classical Hodgkin lymphoma from 60 Chinese patients were analyzed for the expression of cyclin B1, EBV-LMP1, P53 and P16(INK4A) proteins by immunohistochemistry. Cyclin B1 protein was overexpressed in 90.0% (54/60) of this group of classical Hodgkin lymphoma, staining mainly and strongly in cytoplasm but also sparsely and weakly in nucleus of the Hodgkin and Reed-Sternberg (HRS) cells. EBV-LMP1, P53 and P16(INK4A) were overexpressed in 85.0%, 96.7% and 71.7% of Hodgkin lymphoma, respectively. EBV-LMP1, P53 and P16(INK4A) were was noted in the nucleus of HRS cells. Microscopically, cyclin B1 and P53 staining distinguished the HRS cells from the complex background of lymphocytes. Cyclin B1 was positively correlated with EBV-LMP1(P < 0.001) and P53(P < 0.001), but was inversely related to P16(INK4A) (P < 0.05). It is suggested that overexpression of cyclin B1 could play an important role in the evolution of classical Hodgkin lymphoma, and cyclin B1 may be considered as a potential adjunct marker to identify HRS cells in diagnosis and be served as Hodgkin lymphoma-associated antigen in the near future.

Background: Recent advance in genetic studies added the confirmed susceptible loci for type 2 diabetes to eighteen. In this study, we attempt to analyze the independent and joint effect of variants from these loci on type 2 diabetes and clinical phenotypes related to glucose metabolism., Methods/principal Findings: Twenty-one single nucleotide polymorphisms (SNPs) from fourteen loci were successfully genotyped in 1,849 subjects with type 2 diabetes and 1,785 subjects with normal glucose regulation. We analyzed the allele and genotype distribution between the cases and controls of these SNPs as well as the joint effects of the susceptible loci on type 2 diabetes risk. The associations between SNPs and type 2 diabetes were examined by logistic regression. The associations between SNPs and quantitative traits were examined by linear regression. The discriminative accuracy of the prediction models was assessed by area under the receiver operating characteristic curves. We confirmed the effects of SNPs from PPARG, KCNJ11, CDKAL1, CDKN2A-CDKN2B, IDE-KIF11-HHEX, IGF2BP2 and SLC30A8 on risk for type 2 diabetes, with odds ratios ranging from 1.114 to 1.406 (P value range from 0.0335 to 1.37E-12). But no significant association was detected between SNPs from WFS1, FTO, JAZF1, TSPAN8-LGR5, THADA, ADAMTS9, NOTCH2-ADAM30 and type 2 diabetes. Analyses on the quantitative traits in the control subjects showed that THADA SNP rs7578597 was association with 2-h insulin during oral glucose tolerance tests (P = 0.0005, empirical P = 0.0090). The joint effect analysis of SNPs from eleven loci showed the individual carrying more risk alleles had a significantly higher risk for type 2 diabetes. And the type 2 diabetes patients with more risk allele tended to have earlier diagnostic ages (P = 0.0006)., Conclusions/significance: The current study confirmed the association between PPARG, KCNJ11, CDKAL1, CDKN2A-CDKN2B, IDE-KIF11-HHEX, IGF2BP2 and SLC30A8 and type 2 diabetes. These type 2 diabetes risk loci contributed to the disease additively.