Sweet's syndrome or acute febrile neutrophilic dermatosis has been associated with underlying... more Sweet's syndrome or acute febrile neutrophilic dermatosis has been associated with underlying infection, malignancy, inflammatory disease and certain medications. The infection agents associated with this include Streptococcus species, Yersinia species, Chlamydia species, Salmonella species and Helicobacter pylori. We report a case of Sweet's syndrome in a 73-year- old woman following a 2 week course of severe gastroenteritis caused by Campylobacter species. Histological examination of skin lesions showed marked inflammatory infiltrate throughout the dermis, composed of neutrophils and histiocytes. The patient was successfully treated with topical and systemic steroids. To date, this is the first case of Sweet's syndrome to be reported linked to Campylobacter species to our knowledge. Case report A 73-year-old woman with type II diabetes and a history of Duke's colon cancer type A resected 16 years earlier presented with a 3 day history of bilateral conjunctival suff...
Background: Human papillomavirus DNA detection in head and neck squamous cell carcinoma has been ... more Background: Human papillomavirus DNA detection in head and neck squamous cell carcinoma has been linked to improved patient prognosis. The main aims of the study was to test the hypotheses that HPV16 E6/E7 oncogene and p53 function within tumours were associated with the widely reported improved patient survival and prognosis in head and neck cancer. Methods: HPV16 DNA, mRNA and p53 mRNA presence were analysed in a prospective study of 42 unselected HNSCC patients; correlating the data with patient age, tumour staging/grade, treatment response, disease recurrence and survival. Results: HPV16 DNA and HPV16 mRNA were present in 45.2 % and 21.4 % of patients, respectively. There was a significant positive association between the detection of HPV16 E6/E7 mRNA and p53 mRNA (p = 0.032), but this was not replicated for HPV16 DNA. Five-year disease free survival for the whole cohort was 63 % (CI 52.5-73.5 %). Multivariable analysis revealed only HPV16 E6/E7 mRNA expression to have significant prognostic influence (p = 0.04). Conclusions: Our study suggests that HPV16 oncogenic transcriptional activity within HNSCC tumours is associated with improved patient survival and better prognosis in a German population. Simple HPV DNA detection alone did not demonstrate this association. The significant association of full-length (wild-type) p53 with HPV16 E6/E7 mRNA is further evidence for a functional relationship, which could contribute to the widely reported improved survival and prognosis. Larger studies are required to validate the frequency of HPV16 mRNA expression in HNSCC.
Polymorphisms in human leukocyte antigen (HLA) genes have been implicated in the risk for develop... more Polymorphisms in human leukocyte antigen (HLA) genes have been implicated in the risk for developing human papillomavirus (HPV)-associated cervical neoplasia. By comparison with local cadaver controls typed for HLA class I (n = 946) and II (n = 144) antigens, HPV-16-positive high grade vulval intraepithelial neoplasia patients (n = 42) showed significantly different frequencies of HLA-A2 [odds ratio (OR), 2.1; confidence interval (CI), 1.4-3.9], HLA-B7 (OR, 2.6; CI, 1.4-4.7), HLA-DRB1*01(01/02/04) (OR, 0.1; CI, 0.03-0.5), HLA-DRB1*11 (OR, 3.3; CI, 1.4-7.1), HLA-DRB1*13 (OR, 0), HLA-DQB1*05 (OR, 0.2; CI, 0.05-0.6), and HLA-DQB1*03032 (OR, 4.6; CI, 1.5-14.0). With the exception of HLA-B7 and HLA-DRB1*11, these significant differences were also seen comparative to local HPV-16-positive cervical carcinoma patients (n = 114), suggesting a specific immunogenetic contribution that is independent of HPV-16 infection in high-grade vulval intraepithelial neoplasia. Such factors are important ...
Proceedings of the National Academy of Sciences, 1991
We have identified a major T-cell epitope, amino acids 48-54 (DRAHYNI, in one-letter code) in the... more We have identified a major T-cell epitope, amino acids 48-54 (DRAHYNI, in one-letter code) in the E7 open reading frame protein of human papillomavirus (HPV) type 16. Lymph node cells from mice immunized with synthetic peptides containing DRAHYNI proliferated and produced interleukin when challenged in vitro with peptide or whole HPV-16 E7 fusion protein. The T epitope was recognized in association with all five major histocompatibility complex class II I-A and I-E alleles tested. Synthetic peptides consisting of DRAHYNI linked to major B-cell epitopes on the E7 molecule formed immunogens capable of eliciting strong antibody responses to HPV-16 E7. The T epitope could provide help for the production of antibody to several B epitopes simultaneously, including a B epitope of HPV-18 E7 protein. Mice immunized with a peptide containing DRAHYNI and B epitope and, at a later date, infected with recombinant vaccinia E7 virus, displayed secondary antibody responses to E7. Because E7 has a r...
Proceedings of the National Academy of Sciences, 2013
Significance The differential expression of the hypoxia-inducible factor-alpha (HIF-α) isoforms i... more Significance The differential expression of the hypoxia-inducible factor-alpha (HIF-α) isoforms in the skin of mice influences vascular resistance and is correlated with homeostatic regulation of nitric oxide synthesis. A correlation between HIF isoform expression and hypertension was found in skin biopsies from human subjects, and may indicate a mechanism in the etiology of idiopathic hypertension.
HAL is a multidisciplinary open access archive for the deposit and dissemination of scientific re... more HAL is a multidisciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.
Epidermodysplasia verruciformis (EV)-type human papillomavirus (HPV) DNA have been detected by PC... more Epidermodysplasia verruciformis (EV)-type human papillomavirus (HPV) DNA have been detected by PCR in squamous cell carcinomas (SCC) from both organ transplant recipients (OTR) and immunocompetent individuals. Their role in skin cancer remains unclear, and previous studies have not addressed whether the viruses are transcriptionally active. We have used in situ hybridization to investigate the transcriptional activity and DNA localization of HPV. EV-HPV gene transcripts were demonstrated in four of 11 (36%) OTR SCC, one of two (50%) IC SCC, and one of five (20%) OTR warts positive by PCR. Viral DNA co-localized with E2/E4 early region gene transcripts in the middle or upper epidermal layers. Non-EV cutaneous HPV gene transcripts were demonstrated in one of five (20%) OTR SCC and four of 10 (40%) OTR warts. In mixed infections transcripts for both types were detected in two of six (33%) cases. Our results provide evidence of EV-HPV gene expression in SCC; although only a proportion of tumors were positive, the similarly low transcriptional activity in warts suggests this is an underestimate. These observations, together with emerging epidemiological and functional data, provide further reason to focus on the contribution of EV-HPV types to the pathogenesis of cutaneous SCC.
Since its original description, there has been a substantial output of publications related to th... more Since its original description, there has been a substantial output of publications related to the FOXP3 gene. The FOXP3 protein, a member of the forkhead/winged-helix family of transcriptional regulators is a nuclear product and is not expressed in the cell cytoplasm or on the cell surface. Expression of this single transcription factor causes a developmental switch in naïve T cells to a suppressor cell phenotype, more commonly referred to as regulatory T cells (Tregs). Tregs have been intensively studied in various autoimmune diseases, infections and different cancers. An increasing choice of commercially available monoclonal antibodies targeting FOXP3 is now available. This report describes the experience of using two commonly used monoclonal FOXP3 antibodies on formalin-fixed paraffinembedded sections of different organs, including the cervix and vulva. The antibodies targeting different FOXP3 epitopes unexpectedly resulted in significantly different staining patterns. This phenomenon has not been previously reported and is likely to be an important observation.
We describe a middle-aged man with aggressive erythrodermic mycosis fungoides whose responses to ... more We describe a middle-aged man with aggressive erythrodermic mycosis fungoides whose responses to several well-established therapies for the disease were either poor or short-lived. Infusion of antibodies engineered against cells expressing the CD4 molecule produced little response. Total body irradiation coupled with autologous bone marrow transplantation led to an encouraging but unfortunately unsustained improvement.
These guidelines for the management of cutaneous warts have been prepared for dermatologists on b... more These guidelines for the management of cutaneous warts have been prepared for dermatologists on behalf of the British Association of Dermatologists. They present evidence-based guidance for treatment, with identification of the strength of evidence available at the time of preparation of the guidelines, and a brief overview of epidemiological aspects, diagnosis and investigation. Other warty conditions Epidermodysplasia verruciformis Epidermodysplasia verruciformis (EV) is an inherited disorder in which there is a mild defect of cell-mediated 4
Background Human papillomaviruses (HPV) are the aetiological agents of certain benign and maligna... more Background Human papillomaviruses (HPV) are the aetiological agents of certain benign and malignant tumours of skin and mucosae; the most important of which is cervical cancer. Also, the incidence of ano-genital warts, HPV-anal cancer and oropharyngeal cancers are rising. To help ascertain a useful PCR detection protocol for oropharyngeal cancers, we directly compared three commonly used primer sets in detection of HPV from different clinical samples. Methods We compared PGMY09/11, MY09/11 and GP5+/6+ primers sets in PCRs of 34 clinically diagnosed samples of genital warts, cervical brushings (with associated histological diagnosis) and vulval biopsies. All negative samples were subsequently tested using the previously reported PGMY/GP PCR method and amplicons directly sequenced for confirmation and typing. An optimised PCR protocol was then compared to a line blot assay for detection of HPV in 15 oropharyngeal cancer samples. Results PGMY09/11 primers detected HPV presence in more ...
Clinical cancer research : an official journal of the American Association for Cancer Research, 2003
Anogenital intraepithelial neoplasia is a chronic disorder associated with infection by high-risk... more Anogenital intraepithelial neoplasia is a chronic disorder associated with infection by high-risk human papillomavirus (HPV) types. It is frequently multifocal and recurrence after conventional treatment is high. Boosting HPV-specific cell-mediated immune responses may reduce progression to carcinoma and could lead to disease clearance. We have tested the safety, immunogenicity, and efficacy of a recombinant vaccinia candidate vaccine (TA-HPV) in women with anogenital intraepithelial neoplasia. Twelve women, aged 42-54 years with high-grade HPV-positive vulval or vaginal intraepithelial neoplasia of up to 15 years duration, completed a Phase II study of TA-HPV, a live recombinant vaccinia virus, expressing modified versions of the E6 and E7 open reading frames from HPV-16 and HPV-18. The vaccine was well tolerated. Five of 12 (42%) patients showed at least a 50% reduction in total lesion diameter over 24 weeks with 1 patient showing complete regression of her lesion. Overall, 83% of...
Bullous pemphigoid is a blistering skin disorder with increased mortality. We tested whether a st... more Bullous pemphigoid is a blistering skin disorder with increased mortality. We tested whether a strategy of starting treatment with doxycycline gives acceptable short-term blister control while conferring long-term safety advantages over starting treatment with oral corticosteroids. We did a pragmatic, multicentre, parallel-group randomised controlled trial of adults with bullous pemphigoid (three or more blisters at two or more sites and linear basement membrane IgG or C3). Participants were randomly assigned to doxycycline (200 mg per day) or prednisolone (0·5 mg/kg per day) using random permuted blocks of randomly varying size, and stratified by baseline severity (3-9, 10-30, and >30 blisters for mild, moderate, and severe disease, respectively). Localised adjuvant potent topical corticosteroids (<30 g per week) were permitted during weeks 1-3. The non-inferiority primary effectiveness outcome was the proportion of participants with three or fewer blisters at 6 weeks. We ass...
The version in the Kent Academic Repository may differ from the final published version. Users ar... more The version in the Kent Academic Repository may differ from the final published version. Users are advised to check http://kar.kent.ac.uk for the status of the paper. Users should always cite the published version of record.
This study was designed to identify significant differences in gene expression profiles of HPV-po... more This study was designed to identify significant differences in gene expression profiles of HPV-positive (HPV+) and HPV-negative (HPV-) oropharyngeal squamous cell carcinomas (OPSCC) and to better understand the functional and biological effects of HPV infection in the pre-malignant pathway. Twenty-four consecutive patients with locally advanced primary OPSCC were included in a prospective clinical trial. Fresh tissue samples (tumor versus matched normal epithelium) were subjected to whole transcriptome analysis and the results validated on the same cohort with reverse transcription-quantitative real-time PCR (RT-qPCR). In a separate retrospective cohort of twenty-seven OPSCC patients, laser capture micro-dissection of FFPE tissue allowed RNA extraction from adjacent regions of normal epithelium, carcinoma in situ (pre-malignant) and invasive SCC tissue. In all patients, the majority displayed evidence of high risk HPV16 positivity (80.4%). Predictable fold changes of RNA expression ...
Sweet's syndrome or acute febrile neutrophilic dermatosis has been associated with underlying... more Sweet's syndrome or acute febrile neutrophilic dermatosis has been associated with underlying infection, malignancy, inflammatory disease and certain medications. The infection agents associated with this include Streptococcus species, Yersinia species, Chlamydia species, Salmonella species and Helicobacter pylori. We report a case of Sweet's syndrome in a 73-year- old woman following a 2 week course of severe gastroenteritis caused by Campylobacter species. Histological examination of skin lesions showed marked inflammatory infiltrate throughout the dermis, composed of neutrophils and histiocytes. The patient was successfully treated with topical and systemic steroids. To date, this is the first case of Sweet's syndrome to be reported linked to Campylobacter species to our knowledge. Case report A 73-year-old woman with type II diabetes and a history of Duke's colon cancer type A resected 16 years earlier presented with a 3 day history of bilateral conjunctival suff...
Background: Human papillomavirus DNA detection in head and neck squamous cell carcinoma has been ... more Background: Human papillomavirus DNA detection in head and neck squamous cell carcinoma has been linked to improved patient prognosis. The main aims of the study was to test the hypotheses that HPV16 E6/E7 oncogene and p53 function within tumours were associated with the widely reported improved patient survival and prognosis in head and neck cancer. Methods: HPV16 DNA, mRNA and p53 mRNA presence were analysed in a prospective study of 42 unselected HNSCC patients; correlating the data with patient age, tumour staging/grade, treatment response, disease recurrence and survival. Results: HPV16 DNA and HPV16 mRNA were present in 45.2 % and 21.4 % of patients, respectively. There was a significant positive association between the detection of HPV16 E6/E7 mRNA and p53 mRNA (p = 0.032), but this was not replicated for HPV16 DNA. Five-year disease free survival for the whole cohort was 63 % (CI 52.5-73.5 %). Multivariable analysis revealed only HPV16 E6/E7 mRNA expression to have significant prognostic influence (p = 0.04). Conclusions: Our study suggests that HPV16 oncogenic transcriptional activity within HNSCC tumours is associated with improved patient survival and better prognosis in a German population. Simple HPV DNA detection alone did not demonstrate this association. The significant association of full-length (wild-type) p53 with HPV16 E6/E7 mRNA is further evidence for a functional relationship, which could contribute to the widely reported improved survival and prognosis. Larger studies are required to validate the frequency of HPV16 mRNA expression in HNSCC.
Polymorphisms in human leukocyte antigen (HLA) genes have been implicated in the risk for develop... more Polymorphisms in human leukocyte antigen (HLA) genes have been implicated in the risk for developing human papillomavirus (HPV)-associated cervical neoplasia. By comparison with local cadaver controls typed for HLA class I (n = 946) and II (n = 144) antigens, HPV-16-positive high grade vulval intraepithelial neoplasia patients (n = 42) showed significantly different frequencies of HLA-A2 [odds ratio (OR), 2.1; confidence interval (CI), 1.4-3.9], HLA-B7 (OR, 2.6; CI, 1.4-4.7), HLA-DRB1*01(01/02/04) (OR, 0.1; CI, 0.03-0.5), HLA-DRB1*11 (OR, 3.3; CI, 1.4-7.1), HLA-DRB1*13 (OR, 0), HLA-DQB1*05 (OR, 0.2; CI, 0.05-0.6), and HLA-DQB1*03032 (OR, 4.6; CI, 1.5-14.0). With the exception of HLA-B7 and HLA-DRB1*11, these significant differences were also seen comparative to local HPV-16-positive cervical carcinoma patients (n = 114), suggesting a specific immunogenetic contribution that is independent of HPV-16 infection in high-grade vulval intraepithelial neoplasia. Such factors are important ...
Proceedings of the National Academy of Sciences, 1991
We have identified a major T-cell epitope, amino acids 48-54 (DRAHYNI, in one-letter code) in the... more We have identified a major T-cell epitope, amino acids 48-54 (DRAHYNI, in one-letter code) in the E7 open reading frame protein of human papillomavirus (HPV) type 16. Lymph node cells from mice immunized with synthetic peptides containing DRAHYNI proliferated and produced interleukin when challenged in vitro with peptide or whole HPV-16 E7 fusion protein. The T epitope was recognized in association with all five major histocompatibility complex class II I-A and I-E alleles tested. Synthetic peptides consisting of DRAHYNI linked to major B-cell epitopes on the E7 molecule formed immunogens capable of eliciting strong antibody responses to HPV-16 E7. The T epitope could provide help for the production of antibody to several B epitopes simultaneously, including a B epitope of HPV-18 E7 protein. Mice immunized with a peptide containing DRAHYNI and B epitope and, at a later date, infected with recombinant vaccinia E7 virus, displayed secondary antibody responses to E7. Because E7 has a r...
Proceedings of the National Academy of Sciences, 2013
Significance The differential expression of the hypoxia-inducible factor-alpha (HIF-α) isoforms i... more Significance The differential expression of the hypoxia-inducible factor-alpha (HIF-α) isoforms in the skin of mice influences vascular resistance and is correlated with homeostatic regulation of nitric oxide synthesis. A correlation between HIF isoform expression and hypertension was found in skin biopsies from human subjects, and may indicate a mechanism in the etiology of idiopathic hypertension.
HAL is a multidisciplinary open access archive for the deposit and dissemination of scientific re... more HAL is a multidisciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.
Epidermodysplasia verruciformis (EV)-type human papillomavirus (HPV) DNA have been detected by PC... more Epidermodysplasia verruciformis (EV)-type human papillomavirus (HPV) DNA have been detected by PCR in squamous cell carcinomas (SCC) from both organ transplant recipients (OTR) and immunocompetent individuals. Their role in skin cancer remains unclear, and previous studies have not addressed whether the viruses are transcriptionally active. We have used in situ hybridization to investigate the transcriptional activity and DNA localization of HPV. EV-HPV gene transcripts were demonstrated in four of 11 (36%) OTR SCC, one of two (50%) IC SCC, and one of five (20%) OTR warts positive by PCR. Viral DNA co-localized with E2/E4 early region gene transcripts in the middle or upper epidermal layers. Non-EV cutaneous HPV gene transcripts were demonstrated in one of five (20%) OTR SCC and four of 10 (40%) OTR warts. In mixed infections transcripts for both types were detected in two of six (33%) cases. Our results provide evidence of EV-HPV gene expression in SCC; although only a proportion of tumors were positive, the similarly low transcriptional activity in warts suggests this is an underestimate. These observations, together with emerging epidemiological and functional data, provide further reason to focus on the contribution of EV-HPV types to the pathogenesis of cutaneous SCC.
Since its original description, there has been a substantial output of publications related to th... more Since its original description, there has been a substantial output of publications related to the FOXP3 gene. The FOXP3 protein, a member of the forkhead/winged-helix family of transcriptional regulators is a nuclear product and is not expressed in the cell cytoplasm or on the cell surface. Expression of this single transcription factor causes a developmental switch in naïve T cells to a suppressor cell phenotype, more commonly referred to as regulatory T cells (Tregs). Tregs have been intensively studied in various autoimmune diseases, infections and different cancers. An increasing choice of commercially available monoclonal antibodies targeting FOXP3 is now available. This report describes the experience of using two commonly used monoclonal FOXP3 antibodies on formalin-fixed paraffinembedded sections of different organs, including the cervix and vulva. The antibodies targeting different FOXP3 epitopes unexpectedly resulted in significantly different staining patterns. This phenomenon has not been previously reported and is likely to be an important observation.
We describe a middle-aged man with aggressive erythrodermic mycosis fungoides whose responses to ... more We describe a middle-aged man with aggressive erythrodermic mycosis fungoides whose responses to several well-established therapies for the disease were either poor or short-lived. Infusion of antibodies engineered against cells expressing the CD4 molecule produced little response. Total body irradiation coupled with autologous bone marrow transplantation led to an encouraging but unfortunately unsustained improvement.
These guidelines for the management of cutaneous warts have been prepared for dermatologists on b... more These guidelines for the management of cutaneous warts have been prepared for dermatologists on behalf of the British Association of Dermatologists. They present evidence-based guidance for treatment, with identification of the strength of evidence available at the time of preparation of the guidelines, and a brief overview of epidemiological aspects, diagnosis and investigation. Other warty conditions Epidermodysplasia verruciformis Epidermodysplasia verruciformis (EV) is an inherited disorder in which there is a mild defect of cell-mediated 4
Background Human papillomaviruses (HPV) are the aetiological agents of certain benign and maligna... more Background Human papillomaviruses (HPV) are the aetiological agents of certain benign and malignant tumours of skin and mucosae; the most important of which is cervical cancer. Also, the incidence of ano-genital warts, HPV-anal cancer and oropharyngeal cancers are rising. To help ascertain a useful PCR detection protocol for oropharyngeal cancers, we directly compared three commonly used primer sets in detection of HPV from different clinical samples. Methods We compared PGMY09/11, MY09/11 and GP5+/6+ primers sets in PCRs of 34 clinically diagnosed samples of genital warts, cervical brushings (with associated histological diagnosis) and vulval biopsies. All negative samples were subsequently tested using the previously reported PGMY/GP PCR method and amplicons directly sequenced for confirmation and typing. An optimised PCR protocol was then compared to a line blot assay for detection of HPV in 15 oropharyngeal cancer samples. Results PGMY09/11 primers detected HPV presence in more ...
Clinical cancer research : an official journal of the American Association for Cancer Research, 2003
Anogenital intraepithelial neoplasia is a chronic disorder associated with infection by high-risk... more Anogenital intraepithelial neoplasia is a chronic disorder associated with infection by high-risk human papillomavirus (HPV) types. It is frequently multifocal and recurrence after conventional treatment is high. Boosting HPV-specific cell-mediated immune responses may reduce progression to carcinoma and could lead to disease clearance. We have tested the safety, immunogenicity, and efficacy of a recombinant vaccinia candidate vaccine (TA-HPV) in women with anogenital intraepithelial neoplasia. Twelve women, aged 42-54 years with high-grade HPV-positive vulval or vaginal intraepithelial neoplasia of up to 15 years duration, completed a Phase II study of TA-HPV, a live recombinant vaccinia virus, expressing modified versions of the E6 and E7 open reading frames from HPV-16 and HPV-18. The vaccine was well tolerated. Five of 12 (42%) patients showed at least a 50% reduction in total lesion diameter over 24 weeks with 1 patient showing complete regression of her lesion. Overall, 83% of...
Bullous pemphigoid is a blistering skin disorder with increased mortality. We tested whether a st... more Bullous pemphigoid is a blistering skin disorder with increased mortality. We tested whether a strategy of starting treatment with doxycycline gives acceptable short-term blister control while conferring long-term safety advantages over starting treatment with oral corticosteroids. We did a pragmatic, multicentre, parallel-group randomised controlled trial of adults with bullous pemphigoid (three or more blisters at two or more sites and linear basement membrane IgG or C3). Participants were randomly assigned to doxycycline (200 mg per day) or prednisolone (0·5 mg/kg per day) using random permuted blocks of randomly varying size, and stratified by baseline severity (3-9, 10-30, and >30 blisters for mild, moderate, and severe disease, respectively). Localised adjuvant potent topical corticosteroids (<30 g per week) were permitted during weeks 1-3. The non-inferiority primary effectiveness outcome was the proportion of participants with three or fewer blisters at 6 weeks. We ass...
The version in the Kent Academic Repository may differ from the final published version. Users ar... more The version in the Kent Academic Repository may differ from the final published version. Users are advised to check http://kar.kent.ac.uk for the status of the paper. Users should always cite the published version of record.
This study was designed to identify significant differences in gene expression profiles of HPV-po... more This study was designed to identify significant differences in gene expression profiles of HPV-positive (HPV+) and HPV-negative (HPV-) oropharyngeal squamous cell carcinomas (OPSCC) and to better understand the functional and biological effects of HPV infection in the pre-malignant pathway. Twenty-four consecutive patients with locally advanced primary OPSCC were included in a prospective clinical trial. Fresh tissue samples (tumor versus matched normal epithelium) were subjected to whole transcriptome analysis and the results validated on the same cohort with reverse transcription-quantitative real-time PCR (RT-qPCR). In a separate retrospective cohort of twenty-seven OPSCC patients, laser capture micro-dissection of FFPE tissue allowed RNA extraction from adjacent regions of normal epithelium, carcinoma in situ (pre-malignant) and invasive SCC tissue. In all patients, the majority displayed evidence of high risk HPV16 positivity (80.4%). Predictable fold changes of RNA expression ...
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