Type-specific high-risk HPV (hrHPV) infection is related to cervical carcinogenesis. The prevalence of hrHPV infection varies geographically, which might reflect the epidemiological characteristics of cervical cancer among different populations. To establish a foundation for HPV-based screening and vaccination programs in China, we investigated the most recent HPV prevalence and genotypic distributions in different female age groups and geographical regions in China. In 2012, a total of 120,772 liquid-based cytological samples from women enrolled for population- or employee-based cervical screening in 37 Chinese cities were obtained by the Laboratory of Molecular Infectious Diseases of Guangzhou KingMed. A total of 111,131 samples were tested by Hybrid Capture II and the other 9,641 were genotyped using the Tellgenplex™ HPV DNA Assay. The total positive rate for hrHPV was 21.07 %, which ranged from 18.42 % (Nanchang) to 31.94 % (Haikou) and varied by region. The regions of Nanchang, Changsha, Hangzhou, Chengdu, Fuzhou, Guangdong, and Guiyang could be considered the low prevalence regions. Age-specific prevalence showed a “two-peak” pattern, with the youngest age group (15–19 years) presenting the highest hrHPV infection rate (30.55 %), followed by a second peak for the 50–60-year-old group. Overall, the most prevalent genotypes were HPV16 (4.82 %) and HPV52 (4.52 %), followed by HPV58 (2.74 %). Two genotypes HPV6 (4.01 %) and HPV11 (2.29 %) were predominant in the low-risk HPV (lrHPV) type, while the mixed genotypes HPV16 + 52 and HPV52 + 58 were most common in women with multiple infections. This study shows that HPV infection in China has increased to the level of an “HPV-heavy-burden” zone in certain regions, with prevalence varying significantly among different ages and regions. Data from this study represent the most current survey of the nationwide prevalence of HPV infection in China, and can serve as valuable reference to guide nationwide cervical cancer screening and HPV vaccination programs.

/pdf/nationwide-prevalence-of-human-papillomavirus-infection-and-4a2e7ynczh.pdf

Nationwide prevalence of human papillomavirus infection and viral genotype distribution in 37 cities in China

While sequencing studies have provided an improved understanding of the genetic landscape of head and neck squamous cell carcinomas (HNSCC), there remains a significant lack of genetic data derived from non-Caucasian cohorts. Additionally, there is wide variation in HNSCC incidence and mortality worldwide both between and within various geographic regions. These epidemiologic differences are in part accounted for by varying exposure to environmental risk factors such as tobacco, alcohol, high risk human papilloma viruses and betel quid. However, inherent genetic factors may also play an important role in this variability. As limited sequencing data is available for many populations, the involvement of unique genetic factors in HNSCC pathogenesis from epidemiologically diverse groups is unknown. Here, we review current knowledge about the epidemiologic, environmental, and genetic variation in HNSCC cohorts globally and discuss future studies necessary to further our understanding of these differences. Long-term, a more complete understanding of the genetic drivers found in diverse HNSCC cohorts may help the development of personalized medicine protocols for patients with rare or complex genetic events.

/pdf/genetic-determinants-in-head-and-neck-squamous-cell-49thhbhauk.pdf

Genetic determinants in head and neck squamous cell carcinoma and their influence on global personalized medicine

Comparison of oropharyngeal and oral cavity squamous cell cancer incidence and trends in New Zealand and Queensland, Australia

Objectives 
Previous reports suggest a strong association between human papillomavirus (HPV) and the etiology of laryngeal squamous cell carcinoma (LSCC). However, clinical data regarding the HPV infection rate among LSCC patients remain largely inconsistent.
Methods 
In total, 674 LSCC patients from three major hospitals in Shanghai were enrolled in this study. We determined the patients' HPV infection status using immunohistochemistry and the GenoArray HPV genotyping assay and calculated their long-term survival rate using the Kaplan-Meier method.
Results 
The total P16-positive rate according to immunostaining results was 7.57% (51/674). None of the P16-negative patients were HPV-positive according to the HPV genotyping test. The rate of HPV infection among patients with LSCC was 4.9% (33/674). HPV infection was more common among nonsmokers (P<0.05), nondrinkers (P<0.05), and patients with supraglottic LSCC (P<0.05). Of the 33 HPV-positive patients, 28 (84.8%) were infected with HPV-16, 2 with HPV-18, 1 with HPV-31, 1 with HPV-33 and 1 with HPV-45. The 3-year overall survival rate and progression-free survival rate were higher in HPV-positive than HPV-negative patients, but the difference was not statistically significant (76.3% vs. 70.7%, P = 0.30 and 65.1% vs. 58.3%, P = 0.37, respectively).
Conclusion 
HPV was not a main causal factor in LSCC carcinogenesis in this Chinese population. HPV infection did not alter patients' overall survival or progression-free survival rates in this study.

/pdf/human-papillomavirus-infection-in-674-chinese-patients-with-7belj2w6nb.pdf

Human papillomavirus infection in 674 Chinese patients with laryngeal squamous cell carcinoma.

Aim We have recently identified and characterized cancer stem cell (CSC) subpopulations within moderately differentiated buccal mucosal squamous cell carcinoma (MDBMSCC). We hypothesized that these CSCs express components of the renin-angiotensin system (RAS). Methods 3,3-Diaminobenzidine (DAB) immunohistochemical (IHC) staining was performed on formalin-fixed paraffin-embedded MDBMSCC samples to investigate the expression of the components of the RAS: pro(renin) receptor (PRR), angiotensin converting enzyme (ACE), angiotensin II receptor 1 (ATIIR1) and angiotensin II receptor 2 (ATIIR2). NanoString mRNA gene expression analysis and Western Blotting (WB) were performed on snap-frozen MDBMSCC samples to confirm gene expression and translation of these transcripts, respectively. Double immunofluorescent (IF) IHC staining of these components of the RAS with the embryonic stem cell markers OCT4 or SALL4 was performed to demonstrate their localization in relation to the CSC subpopulations within MDBMSCC. Results DAB IHC staining demonstrated expression of PRR, ACE, ATIIR1 and ATIIR2 in MDBMSCC. IF IHC staining showed that PRR was expressed by the CSC subpopulations within the tumor nests, the peri-tumoral stroma and the endothelium of the microvessels within the peri-tumoral stroma. ATIIR1 and ATIIR2 were localized to the CSC subpopulations within the tumor nests and the peri-tumoral stroma, while ACE was localized to the endothelium of the microvessels within the peri-tumoral stroma. WB and NanoString analyses confirmed protein expression and transcription activation of PRR, ACE and ATIIR1 but not of ATIIR2, respectively.

/pdf/cancer-stem-cells-in-moderately-differentiated-buccal-n1xhkvtx21.pdf

Cancer Stem Cells in Moderately Differentiated Buccal Mucosal Squamous Cell Carcinoma Express Components of the Renin-Angiotensin System.

Several types of HPVs have been shown to be associated with the development of malignant cancers in various head and neck tumors. More information on the HPV prevalence in patients with head and neck squamous cell carcinomas (SCCs) need to be obtained. In this study, formalin-fixed and paraffin-embedded tissues of 93 pathologically diagnosed head and neck SCC patients were collected from Peking University Cancer Hospital. HPV DNA sequences in tumor tissues were screened by a commercial Luminex technique for HPVs and HPV-specific PCR assays. Presence of HPV16/18 oncoprotein in tumor tissues was assessed by immunohistochemistry (IHC) with HPV16/18 E6-specific antibodies. Of the 93 patients, 16 (17.2%) cases were found to be HPV DNA-positive, including 7 HPV18-positive, 8 HPV16-positive and 1 HPV52-positive. IHC assays demonstrated that 31.2% (29/93) tested sections showed positive signals in the tumor cells. The total positive rate of HPV genome and its encoding products in the tested samples was 44.1% (41/93). Further analyses revealed that HPV infections in head and neck SCCs were significantly related with the tumor anatomic sites, showing decreasing tendency from outside (lip cancer) to inside (laryngeal cancer), but had no correlation with pathological, clinical grades and age of the patients. In all, HPV infections are commonly identified in the tumor tissues of patients with head and neck SCCs, in which HPV16 and 18 are the most prevalent HPV genotypes. Direct detection of high-risk HPV oncoprotein by IHC may be a good tool for classifying a tumor as truly HPV-associated.

/pdf/the-distribution-of-human-papillomavirus-in-tissues-from-2sy1xxy2eb.pdf

The distribution of human papillomavirus in tissues from patients with head and neck squamous cell carcinoma.

To investigate the possible associations between mutations in TP53 and phenotypes of single-nucleotide polymorphisms (SNPs) in codon 72 (SNP72) with the expression profiles of p53 and human papillomavirus (HPV) infection, 93 pathologically diagnosed head and neck squamous cell carcinomas (HNSCCs) were included for study. Using PCR and direct sequencing, 45 TP53 mutations in 35 cases (37.6%) were confirmed out of the 93 HNSCCs. P53 immunohistochemistry (IHC) confirmed 34 (36.6%) cases with positive staining, including 22 cases with strong and 12 with weak positivity. IARC database and software analysis showed similar results that most of the mutated p53 proteins lost their normal function. Further statistical analysis found a negative correlation between p53 IHC and HPV IHC in the tissues from the group of other HNSCCs (of various sites other than the larynx) but not in the tissues from the laryngeal carcinomas. Analyses of SNP72 showed that the patients with the Arg phenotype had a significantly older age at disease onset when compared to patients with the Pro phenotype, particularly in the group of other HNSCCs. In addition, all cases with strong staining for p53 in the laryngeal carcinoma group had the Pro phenotype and all tumors with poor pathological differentiation in the group of other HNSCCs had the Pro phenotype. These data indicate that the profiles of TP53 mutations, SNP72 polymorphism, p53 IHC and HPV E6 IHC are distinct between the groups of laryngeal carcinoma and other HNSCCs.

/pdf/associations-of-tp53-mutations-codon-72-polymorphism-and-46nyrt679f.pdf

Associations of TP53 mutations, codon 72 polymorphism and human papillomavirus in head and neck squamous cell carcinoma patients.

Objective To analyze the infection of human papillomavirus in lip squamous cell carcinoma patients.Methods The pathological samples of 9 clinical diagnosed lip cancer patients were collected.Lunimex and PCR techniques were used to detect the HPV gene infection and immunohistochemistry method was used to analyze the HPV protein expression in the samples.Results In the 9 cases,1 was positive for HPV16 gene and 7 were positive for HPV16/18 E6 protein expression.The total positive rate was about 8/9.Conclusion The high HPV infection rate in lip cancer patients in the study indicated indirectly that the importance of the direct contact to the infection of HPV what was the basis for pathogenesis of the lip squamous cell carcinoma.

Key words: 
Lip neoplasms; Carcinoma,squamous cell; Papillomavirus,human

The analysis of human papillomavirus infection in lip squamous cell carcinoma patients

Objective To analyze the infection of human papillomavirus in laryngeal squamous cell carcinoma patients.Methods The pathological samples of 64 clinical diagnosed laryngeal squamous cell carcinoma patients were collected.Lunimex and PCR techniques were used to detect the HPV gene infection and immunohistochemistry method was used to analyze the HPV protein expression in the samples.Results In the 64 cases,7 were positive for HPV infection by Luminex and PCR tests.18 were positive for HPV16/18 E6 protein expression.The total positive rate was about 39.1％.Conclusion The high HPV infection rate in laryngeal squamous cell carcinoma patients in the study indicated indirectly that the importance of the HPV infection in pathogenesis of the laryngeal squamous cell carcinoma.

Key words: 
Laryngeal neoplasms;  Carcinoma,squamous cell;  Papilomavirus,human

Analysis of the human papillomavirus in laryngeal squamous cell carcinoma patients

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The distribution of human papillomavirus in tissues from patients with head and neck squamous cell carcinoma.

Associations of TP53 mutations, codon 72 polymorphism and human papillomavirus in head and neck squamous cell carcinoma patients.

The analysis of human papillomavirus infection in lip squamous cell carcinoma patients

Analysis of the human papillomavirus in laryngeal squamous cell carcinoma patients