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Al Fadel AM, Jakobsen KK, Jensen LH, Carlander ALF, Grønhøj C, von Buchwald C. The epidemiological trends and survival of HPV-related oropharyngeal cancer other than tonsils and base of tongue - a systematic review and meta-analysis. Oral Oncol 2025; 165:107311. [PMID: 40286702 DOI: 10.1016/j.oraloncology.2025.107311] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2024] [Revised: 04/08/2025] [Accepted: 04/13/2025] [Indexed: 04/29/2025]
Abstract
IMPORTANCE Human papillomavirus (HPV) is a well-established cause of oropharyngeal squamous cell carcinoma (OPSCC) located in the tonsils and base of tongue, but the association with other oropharyngeal subsites (otherOPSCC) remains unclear. This study aimed to examine the worldwide prevalence of HPV in otherOPSCC and its impact on survival utilizing the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. METHODS The study outcomes and measures were planned at PROSPERO in advance. PubMed was searched from the earliest available record to September 1st, 2023. We included studies reporting otherOPSCC and known HPV-status. Exclusion criteria were (1) studies with ten or less otherOPSCC cases (2) studies with unspecified OPSCC subsite or with unknown primary tumor location (3) review articles, meta-analyses, and case reports (4) studies that focused exclusively on HPV+ or HPV- OPSCC. Two authors independently extracted the data.Risk of bias assessment was done using the ROBINS-E tool. The meta-analysis was conducted utilizing a random-effects model. RESULTS A total of 42 studies met the inclusion criteria comprising 20 unique cohorts with a total of 6442 patients (range 11-3776). A meta-analysis showed an overall HPV prevalence of 20% (95% CI 13% 30%). We found no significant differences in the 5-year OS between HPV + otherOPSCC and HPV- otherOPSCC (56% [95% CI 29% 80%] vs 45% [95% CI 41% 49%], p = 0.43). CONCLUSION Our study revealed a low HPV prevalence in otherOPSCC (20%). HPV is not a useful prognostic factor in other OPSCCs than palatine tonsils and base of tongue locations.
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Affiliation(s)
- Anas Mohammad Al Fadel
- Department of Otolaryngology and Audiology, Head and Neck Surgery, Rigshospitalet, Copenhagen University Hospital, Denmark.
| | - Kathrine Kronberg Jakobsen
- Department of Otolaryngology and Audiology, Head and Neck Surgery, Rigshospitalet, Copenhagen University Hospital, Denmark
| | - Lasse Holmgaard Jensen
- Department of Otolaryngology and Audiology, Head and Neck Surgery, Rigshospitalet, Copenhagen University Hospital, Denmark
| | - Amanda-Louise Fenger Carlander
- Department of Otolaryngology and Audiology, Head and Neck Surgery, Rigshospitalet, Copenhagen University Hospital, Denmark
| | - Christian Grønhøj
- Department of Otolaryngology and Audiology, Head and Neck Surgery, Rigshospitalet, Copenhagen University Hospital, Denmark
| | - Christian von Buchwald
- Department of Otolaryngology and Audiology, Head and Neck Surgery, Rigshospitalet, Copenhagen University Hospital, Denmark
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Uhlrich E, Klijanienko J, Martin J, Jeannot E, Vincent-Salomon A, Freneaux P, Le Tourneau C, Choussy O, Dubray-Vautrin A. Prevalence of human papilloma virus in head and neck mucous squamous cell carcinoma and genotypes by location: an observational study. Eur J Cancer Prev 2024:00008469-990000000-00184. [PMID: 39498745 DOI: 10.1097/cej.0000000000000933] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2024]
Abstract
Human papillomavirus (HPV) is a factor in oropharyngeal cancer, but data regarding other head and neck locations are scarce in France. The main objective of the study was to determine the prevalence of HPV in head and neck cancers at all locations. As a secondary objective, we aimed to investigate the HPV genotypes. We retrospectively included in a tertiary center between 2014 and 2020 mucosal squamous cell carcinomas of the head and neck in adult. First outcome was the prevalence of HPV cancer. Secondary outcomes were overall survival (OS) at 2 and 5 years and disease-free survival (DFS). A total of 508 patients were enrolled, resulting in 537 cases of mucous squamous cell carcinoma of the head and neck (n = 29 synchronous carcinomas). Clinical, pathological, and survival data were collected, and a double PCR for HPV with genotyping was performed on most of the samples. The HPV prevalence in the cohort was 28.2%, with HPV 16 being the predominant genotype (87%). However, HPV-positive status did not significantly improve OS at 2 and 5 years or DFS (P = 0.1, P = 0.64, and P = 0.07, respectively). It was also observed that HPV-positive patients had significantly fewer second tumor localizations (P < 0.01). The prevalence of HPV continues to rise, and the complexities surrounding HPV status and its association with clinical outcomes in head and neck squamous cell carcinoma highlight the impact of vaccination.
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Affiliation(s)
- Emilie Uhlrich
- Department of Oto-Rhino-Laryngology, Head & Neck Surgery
| | | | - Joey Martin
- Department of Oto-Rhino-Laryngology, Head & Neck Surgery
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Cui M, Cheng J, Cheng H, Zhao M, Zhou D, Zhang M, Jia J, Luo L. Characteristics of human papillomavirus infection among oropharyngeal cancer patients: A systematic review and meta-analysis. Arch Oral Biol 2024; 157:105830. [PMID: 37924712 DOI: 10.1016/j.archoralbio.2023.105830] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2023] [Revised: 10/19/2023] [Accepted: 10/25/2023] [Indexed: 11/06/2023]
Abstract
OBJECTIVE This study aimed to explore the characteristics of human papillomavirus (HPV) in oropharyngeal carcinoma (OPC), in order to provide a new theoretical basis for the prevention, treatment, and management of OPC. METHODS The electronic databases were searched available publications relevant to HPV infection and OPC. Studies were collected until July, 2023. The effect sizes were combined using R 4.2.2 software. Subgroup and sensitivity analyses were performed to explore the sources of heterogeneity. Funnel plot and Egger's test were used to assess the publication bias. RESULTS Seventy-one studies were included with 10,908 OPC patients. The pooled prevalence of HPV and HR-HPV infection was 44.22% and 43.94%, respectively. The genotypes of HR-HPV were HPV16 (37.24%), HPV33 (2.44%), HPV18 (1.64%), HPV35 (1.53%), and HPV58 (0.89%). The highest HPV infection was in North America (66.87%), Oceania (43.09%), and Europe (41.49%), lowest in Africa (4.89%). Females exhibited higher HPV infection (43.18% vs 34.59% in males). Top subsites of HPV infection was tonsil (45.78%), followed by base of tongue (36.66%). Infection was higher in OPC patients aged > 60 (38.15%) than < 60 (34.73%). The prevalence of HPV infection in stage I-II of OPC patients is higher than that in stage III-IV. CONCLUSIONS HPV genotyping (16, 18, 33, 35, 58) is a key factor in the prevention and treatment of OPC. Identifying tonsils, base of tongue, and soft palate as common subsites to improve early detection. Elderly women with high HPV infection require attention to risk management and health education for prevention.
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Affiliation(s)
- Meimei Cui
- Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, China; Department of Pathology, Weifang Medical University, Weifang, China
| | - Jinling Cheng
- Digestive Department, Shandong Second Provincial General Hospital, Jinan, China
| | - Huijuan Cheng
- Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, China
| | - Ming Zhao
- Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, China; School of Public Health, Jiamusi University, Jiamusi, China
| | - Dan Zhou
- Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, China; School of Public Health, Jiamusi University, Jiamusi, China
| | - Min Zhang
- Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, China; School of Public Health, Jiamusi University, Jiamusi, China
| | - Jingjing Jia
- Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, China; Department of Basic medicine, Jiamusi University, China
| | - Limei Luo
- Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, China.
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Fonsêca TC, Jural LA, Marañón-Vásquez GA, Magno MB, Roza ALOC, Ferreira DMTP, Maia LC, Romañach MJ, Agostini M, Abrahão AC. Global prevalence of human papillomavirus-related oral and oropharyngeal squamous cell carcinomas: a systematic review and meta-analysis. Clin Oral Investig 2023; 28:62. [PMID: 38158517 DOI: 10.1007/s00784-023-05425-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2023] [Accepted: 11/21/2023] [Indexed: 01/03/2024]
Abstract
OBJECTIVE To conduct a systematic review to determine the global prevalence of HPV in oral squamous cell carcinoma (OSCC) and oropharyngeal squamous cell carcinoma (OPSCC). MATERIALS AND METHODS Literature was searched through October 2022 in main databases to address the question "What is the global prevalence of Human Papillomavirus in oral and oropharyngeal cancer?" Studies had to identify HPV by PCR, ISH, or p16 immunohistochemistry to be eligible. Quality was assessed using the JBI checklist for prevalence studies. Meta-analyses were performed, and reporting followed PRISMA guidelines. RESULTS Sixty-five studies were included, and most of them had methodological limitations related to sampling and the HPV detection tool. The pooled prevalence of HPV-positivity was 10% (event rate = 0.1; 95% CI: 0.07, 0.13; P < 0.01; I2 = 88%) in the oral cavity and 42% (event rate = 0.42; 95% CI: 0.36, 0.49; P = 0.02; I2 = 97%) in oropharynx. The highest HPV prevalence in OSCC was reached by Japan, meanwhile, in OPSCC, Finland and Sweden were the most prevalent. HPV16 is the genotype most frequent with 69% in OSCC and 89% in OPSCC, being the tonsils the intraoral location more affected by HPV (63%, p < 0.01, I2 76%). CONCLUSION The evidence points to an apparent burden in HPV-related OPSCC, mostly in North America, Northern Europe, and Oceania, especially due to the HPV16 infection suggesting different trends across continents. CLINICAL RELEVANCE This updated systematic review and meta-analysis provide sufficient evidence about the global HPV prevalence in OSCC and OPSCC and the most frequent HPV subtype worldwide.
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Affiliation(s)
- Thamyres Campos Fonsêca
- Department of Oral Diagnosis and Pathology, School of Dentistry, Federal University of Rio de Janeiro (UFRJ), Avenida Professor Rodolpho Paulo Rocco, 325, 1º Andar. Cidade Universitária, Ilha Do Fundão, Rio de Janeiro, Brazil
| | - Lucas Alves Jural
- Department of Pediatric Dentistry and Orthodontics, School of Dentistry, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
| | - Guido Artemio Marañón-Vásquez
- Department of Pediatric Dentistry and Orthodontics, School of Dentistry, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
| | - Marcela Baraúna Magno
- Department of Pediatric Dentistry and Orthodontics, School of Dentistry, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
| | | | | | - Lucianne Cople Maia
- Department of Pediatric Dentistry and Orthodontics, School of Dentistry, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
| | - Mário José Romañach
- Department of Oral Diagnosis and Pathology, School of Dentistry, Federal University of Rio de Janeiro (UFRJ), Avenida Professor Rodolpho Paulo Rocco, 325, 1º Andar. Cidade Universitária, Ilha Do Fundão, Rio de Janeiro, Brazil
| | - Michelle Agostini
- Department of Oral Diagnosis and Pathology, School of Dentistry, Federal University of Rio de Janeiro (UFRJ), Avenida Professor Rodolpho Paulo Rocco, 325, 1º Andar. Cidade Universitária, Ilha Do Fundão, Rio de Janeiro, Brazil
| | - Aline Correa Abrahão
- Department of Oral Diagnosis and Pathology, School of Dentistry, Federal University of Rio de Janeiro (UFRJ), Avenida Professor Rodolpho Paulo Rocco, 325, 1º Andar. Cidade Universitária, Ilha Do Fundão, Rio de Janeiro, Brazil.
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Associations of Body Mass Index and Waist Circumference with the Risk of Head and Neck Cancer: A National Population-Based Study. Cancers (Basel) 2022; 14:cancers14163880. [PMID: 36010881 PMCID: PMC9405652 DOI: 10.3390/cancers14163880] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2022] [Revised: 08/08/2022] [Accepted: 08/10/2022] [Indexed: 12/26/2022] Open
Abstract
Background: We investigated the association between BMI and HNC subtype incidence in a cohort study of ten million people, adjusting for the effect of smoking and drinking. We also investigated the relationship between waist circumference (WC) and HNC subtype. Methods: All data used in this study originated from the Korean National Health Insurance Service database. We analysed subjects who had undergone health check-ups in 2009 and monitored subjects until 2018 (n = 10,585,852). Finally, 9,598,085 subjects were included after exclusions. We collected variables that could affect the risk of HNC. Cox proportional hazards regression analysis was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: The overall incidence of HNC was higher in the low BMI category (BMI < 18.5 according to WHO recommendations for Asian people) (HR: 1.322; 95% CI: 1.195−1.464) compared with the normal BMI category. Among the HNC cases, the incidence rates of laryngeal (HR: 1.3; 95% CI: 1.085−1.558), oral cavity (HR: 1.277; 95% CI: 1.011−1.611), and oropharyngeal (HR: 1.584; 95% CI: 1.25−2.008) cancers were higher in the low BMI category compared with the normal BMI category. No significant association was detected between low BMI and sinus cancer, salivary gland cancer, or nasopharyngeal cancer. The low WC category (<80 cm in men and <75 cm in women) was related to a risk of hypopharyngeal (HR: 1.268; 95% CI: 1.061−1.514) and laryngeal (HR: 1.118; 95% CI: 1.007−1.241) cancers. The HR for occurrence of HNC was high in underweight participants according to smoking status (1.219 for never smoker vs. 1.448 for ever smoker, p for interaction = 0.0015) and drinking status (1.193 for never drinker vs. 1.448 for ever drinker, p for interaction = 0.0044). Conclusions: Low BMI was associated with the risk of some types of HNC. The results of this study could assist etiological investigations and prevention strategies.
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Jun HW, Ji YB, Song CM, Myung JK, Park HJ, Tae K. Positive Rate of Human Papillomavirus and Its Trend in Head and Neck Cancer in South Korea. Front Surg 2022; 8:833048. [PMID: 35127812 PMCID: PMC8814325 DOI: 10.3389/fsurg.2021.833048] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2021] [Accepted: 12/29/2021] [Indexed: 11/13/2022] Open
Abstract
Introduction This study aimed to investigate the positive rate of human papillomavirus (HPV) and its trend in head and neck squamous cell carcinoma (HNSCC) in South Korea and to evaluate the clinical differences between HPV-positive and -negative tumors. Methods We studied 300 patients with HNSCC arising in the oropharynx (n = 77), oral cavity (n = 65), larynx (n = 106), hypopharynx (n = 40), and sinonasal cavity (n = 12), treated in a tertiary university hospital in South Korea from January 2008 to July 2020. HPV status was determined using p16 immunohistochemical staining of formalin-fixed paraffin-embedded tissues. Results Of the 300 patients with HNSCC, the positive rate of p16 was 30.3% (91/300). The p16 positive rate was 70.1, 13.9, 20.8, 15, and 0% in the oropharynx, oral cavity, larynx, hypopharynx, and sinonasal cavity, respectively. HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) patients were significantly younger than HPV-negative OPSCC patients. The positive rate of HPV in OPSCC has increased over time from 2008 to 2020, but has not changed significantly in the other primary sites. The disease-free survival curve of HPV-positive OPSCC was significantly better than that of HPV-negative tumors. Conclusion The positive rate of HPV in Korean patients with OPSCC is significantly high (70.1%), similar to that in North America and Europe, and has increased abruptly in the past 12 years.
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Affiliation(s)
- Hyun Woong Jun
- Department of Otolaryngology-Head and Neck Surgery, College of Medicine, Hanyang University, Seoul, South Korea
| | - Yong Bae Ji
- Department of Otolaryngology-Head and Neck Surgery, College of Medicine, Hanyang University, Seoul, South Korea
| | - Chang Myeon Song
- Department of Otolaryngology-Head and Neck Surgery, College of Medicine, Hanyang University, Seoul, South Korea
| | - Jae Kyung Myung
- Department of Pathology, College of Medicine, Hanyang University, Seoul, South Korea
| | - Hae Jin Park
- Department of Radiation Oncology, College of Medicine, Hanyang University, Seoul, South Korea
| | - Kyung Tae
- Department of Otolaryngology-Head and Neck Surgery, College of Medicine, Hanyang University, Seoul, South Korea
- *Correspondence: Kyung Tae
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The role of human papilloma virus test in men: First exhaustive review of literature. Actas Urol Esp 2020; 44:86-93. [PMID: 31874781 DOI: 10.1016/j.acuro.2019.08.010] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2019] [Revised: 07/09/2019] [Accepted: 08/27/2019] [Indexed: 01/02/2023]
Abstract
Human papilloma virus (HPV) infection is the most common sexually transmitted infection worldwide. There is a high detection rate in sexually active young people but the risk, in males, persists over years. Currently, the American Center for Disease Control and Prevention does not recommend the evaluation of men for HPV and, the extant bibliography, backs up this stance for several reasons. Objective of the paper was to evaluate the usefulness of HPV detection methods for men; A comprehensive and exhaustive review of the literature was performed. Many are methods for HPV detection used in cervical cancer screening as well as in the study and management of patients with cytological alterations of the lower genital tract. Need for HPV detection methods in men are numerous: screening for both partner/gender; anogenital warts; recurrent respiratory papillomatosis; HPV-related cancer in men; fertility. No HPV test for men has been approved by the FDA, nor has any test been approved for detection of the virus in areas other than the cervix. Many are methods for HPV detection that have shown their usefulness in some of the pathologies associated with male HPV but, despite this, none of them has been approved for man.
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Abdel-Rahman O. Prognostic value of HPV status among patients with hypopharyngeal carcinoma: a population-based study. Clin Transl Oncol 2020; 22:1645-1650. [PMID: 31939101 DOI: 10.1007/s12094-020-02289-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2019] [Accepted: 01/02/2020] [Indexed: 02/08/2023]
Abstract
OBJECTIVE To clarify the prognostic role of human papilloma virus (HPV) status among patients with hypopharyngeal carcinoma. METHODS Surveillance, Epidemiology and End Results (SEER) HPV head and neck cancer database has been accessed and cases with hypopharyngeal squamous cell carcinoma with known HPV status were retrieved. Kaplan-Meier survival estimates were used to evaluate the impact of HPV status on overall survival outcomes of included patients and multivariable cox regression analysis was used to assess the impact of HPV status on overall and head and neck cancer-specific survival. RESULTS A total of 1157 patients' records with hypopharyngeal carcinoma were included in the current analysis. Using Kaplan-Meier survival estimates, patients with HPV positive status seem to have better overall survival compared to patients with HPV negative status (P < 0.01). When stratified by stage, patients with HPV positive regional and distant disease have better overall survival compared to patients with HPV negative regional and distant disease (P < 0.01 for both categories). The same observation cannot be confirmed for patients with localized disease (P = 0.15). Using multivariable Cox regression analysis, HPV positive status seems to be associated with better overall survival (HR for HPV negative versus HPV positive status: 1.76; 95% CI 1.39-2.24; P < 0.01) and cancer-specific survival (HR for HPV negative versus HPV positive status: 1.54; 95% CI 1.12-2.11; P < 0.01). CONCLUSIONS Patients with HPV positive hypopharyngeal carcinoma seem to have better overall and cancer-specific survival compared to patients with HPV negative hypopharyngeal carcinoma.
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Affiliation(s)
- O Abdel-Rahman
- Department of Oncology, Cross Cancer Institute, University of Alberta, Edmonton, AB, T6G 1Z2, Canada.
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Surov A, Meyer HJ, Höhn AK, Winter K, Sabri O, Purz S. Associations Between [ 18F]FDG-PET and Complex Histopathological Parameters Including Tumor Cell Count and Expression of KI 67, EGFR, VEGF, HIF-1α, and p53 in Head and Neck Squamous Cell Carcinoma. Mol Imaging Biol 2019; 21:368-374. [PMID: 29931433 DOI: 10.1007/s11307-018-1223-x] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/28/2022]
Abstract
PURPOSE Head and neck squamous cell carcinoma (HNSCC) is one of common cancers worldwide. Positron emission tomography (PET) with 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) is increasingly used for diagnosing and staging, as well as for monitoring of treatment of HNSCC. PET parameters like maximum and mean standard uptake values (SUVmax, SUVmean) can predict the behavior of HNSCC. The purpose of this study was to analyze possible associations between these PET parameters and clinically relevant histopathological features in patients with HNSCC. PROCEDURES Overall, 22 patients, mean age, 55.2 ± 11.0 years, with different HNSCC were acquired. Low grade (G1/2) tumors were diagnosed in 10 cases (45 %) and high grade (G3) tumor in 12 (55 %) patients. In all cases, whole body PET was performed. For this study, the following specimen stainings were performed: MIB-1 staining (KI 67 expression), epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), tumor suppressor protein p53, hypoxia-inducible factor (HIF)-1α, and human papilloma virus (p16 expression). All stained specimens were digitalized and analyzed by using the ImageJ software 1.48v. Spearman's correlation coefficient (ρ) was used to analyze associations between investigated parameters. P values <0.05 were taken to indicate statistical significance. RESULTS P16-negative tumors showed statistically significant higher SUVmax (ρ = 0.006) and SUVmean values (ρ = 0.002) in comparison to p16-positive carcinomas. No significant differences were identified in the analyzed parameters between poorly and moderately/well-differentiated tumors. In overall sample, there were no statistically significant correlations between the [18F]FDG-PET and histopathological parameters. Also, in G1/2 tumors, no significant correlations were identified. In G3 carcinomas, cell count correlated statistical significant with SUVmax (p = 0.580, P = 0.048) and SUVmean (ρ = 0.587, P = 0.045). CONCLUSION Associations between [18F]FDG-PET parameters and different histopathological features in HNSCC depend significantly on tumor grading. In G1/2 carcinomas, there were no significant correlations between [18F]FDG-PET parameters and histopathology. In G3 lesions, SUVmax and SUVmean reflect tumor cellularity.
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Affiliation(s)
- Alexey Surov
- Department of Diagnostic and Interventional Radiology, University Hospital of Leipzig, Liebigstrasse 20, 04103, Leipzig, Germany.
| | - Hans Jonas Meyer
- Department of Diagnostic and Interventional Radiology, University Hospital of Leipzig, Liebigstrasse 20, 04103, Leipzig, Germany
| | - Anne-Kathrin Höhn
- Department of Pathology, University Hospital of Leipzig, Liebigstrasse 20, 04103, Leipzig, Germany
| | - Karsten Winter
- Institute of Anatomy, University Hospital of Leipzig, Liebigstrasse 20, 04103, Leipzig, Germany
| | - Osama Sabri
- Department of Nuclear Medicine, University Hospital of Leipzig, Liebigstraße 18, 04103, Leipzig, Germany
| | - Sandra Purz
- Department of Nuclear Medicine, University Hospital of Leipzig, Liebigstraße 18, 04103, Leipzig, Germany
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Götz C, Bischof C, Wolff KD, Kolk A. Detection of HPV infection in head and neck cancers: Promise and pitfalls in the last ten years: A meta-analysis. Mol Clin Oncol 2019; 10:17-28. [PMID: 30655973 PMCID: PMC6313947 DOI: 10.3892/mco.2018.1749] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2017] [Accepted: 08/09/2018] [Indexed: 12/16/2022] Open
Abstract
The current controversial discussion on the disease-specific survival of patients with human papillomavirus (HPV)-positive (+) and -negative (-) squamous cell carcinoma (SCC) of the head neck region was the motivation for the present meta-analysis. Different detection methods for HPV are available, though these often lack sensitivity. As a consequence, there may be false interpretation of HPV positivity. A bias concerning HPV status and therefore also survival rates is serving a non-durable relevance in the discussion of tailored therapies. A literature search was performed via the online database PubMed/NCBI, and data extraction and statistical analysis were conducted. A total of 139 studies published between 2004 and 2014 were evaluated in the present meta-analysis. The HPV detection methods, patient characteristics, tumor localizations and stages, as well as (neo-) adjuvant therapies and survival times were analyzed. The average incidence rates of HPV+ patients with oropharyngeal tumors were higher than those of patients with cancers of other regions of the head and neck. Upon evaluating the results of different detection methods no significant differences were identified. We have compared the HPV incidence rates of each detection method, when studies have used more than one. Regarding overall survival, the pooled adjusted hazard ratio (HR) for oropharyngeal SCC was 0.31 [95% confidence interval (CI)=0.27-0.36]. Unfortunately, only 3 equivalent studies were available on nonoropharyngeal tumors, for which the pooled adjusted HR was 1 (95% CI=0.73-1.36). Overall, the evaluation demonstrated that the survival rates reported in numerous studies were not evaluated multifactorially and important confounders were excluded from the statistics. The HPV detection methods used were often not sufficient in representing HPV positivity. In addition, oropharyngeal and oral SCCs were assessed together in the localization. The widely differing number of HPV+ patients in each of the various studies may be explained by insufficient detection methods and by a lack of localization distinction. The considerations of a tailored therapy according to HPV status should be rejected based on the present information. The previously published studies should be read critically and do not represent a basis for therapeutic decisions.
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Affiliation(s)
- Carolin Götz
- Department of Oral and Maxillofacial Surgery, Technical University of Munich, Klinikum Rechts der Isar, D-81675 Munich, Germany
| | - Clara Bischof
- Department of Oral and Maxillofacial Surgery, Technical University of Munich, Klinikum Rechts der Isar, D-81675 Munich, Germany
| | - Klaus-Dietrich Wolff
- Department of Oral and Maxillofacial Surgery, Technical University of Munich, Klinikum Rechts der Isar, D-81675 Munich, Germany
| | - Andreas Kolk
- Department of Oral and Maxillofacial Surgery, Technical University of Munich, Klinikum Rechts der Isar, D-81675 Munich, Germany
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11
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Smoking impact on HPV driven head and neck cancer’s oncological outcomes? Oral Oncol 2018; 82:131-137. [DOI: 10.1016/j.oraloncology.2018.05.007] [Citation(s) in RCA: 38] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2018] [Accepted: 05/12/2018] [Indexed: 12/21/2022]
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12
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Human papillomavirus prevalence and clinicopathological associations in oropharyngeal squamous cell carcinoma in the Lebanese population. The Journal of Laryngology & Otology 2018; 132:636-641. [PMID: 29954474 DOI: 10.1017/s0022215118001019] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
OBJECTIVES To evaluate for the first time the prevalence of human papillomavirus in oropharyngeal squamous cell carcinoma in a Middle-Eastern population, and to determine associations between human papillomavirus profiles and clinicopathological characteristics. METHODS A retrospective chart review was conducted of all patients treated for oropharyngeal squamous cell carcinoma at the Hotel Dieu de France University Hospital (Beirut, Lebanon) between January 2010 and 2016. Existing formalin-fixed paraffin-embedded tumour samples were analysed. Human papillomavirus DNA viral load and p16 expression were evaluated using polymerase chain reaction and immunohistochemistry respectively. RESULTS Thirty patients (mean age of 60 years) were included. Twenty-seven per cent of patients were p16-positive/human papillomavirus DNA positive, 53 per cent were p16-negative/human papillomavirus DNA negative and 20 per cent were p16-positive/human papillomavirus DNA negative. Human papillomavirus 16 was the most frequent subtype (75 per cent). Smoking and alcohol consumption were significantly lower in the human papillomavirus positive group compared to the human papillomavirus negative group (p = 0.049 and 0.004, respectively). CONCLUSION Human papillomavirus rate was lower than reported rates in Western populations. Possible explanations include differences in social and cultural behaviours.
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Delagranda A, Leterme G, Chirpaz E, Ferdynus C, Fernandez C, Rubin F. Epidemiological features of cancers of the oral cavity, oropharynx, hypopharynx and larynx cancer in Réunion Island. Eur Ann Otorhinolaryngol Head Neck Dis 2018; 135:175-181. [DOI: 10.1016/j.anorl.2018.01.008] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/17/2022]
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Shield KD, Marant Micallef C, de Martel C, Heard I, Megraud F, Plummer M, Vignat J, Bray F, Soerjomataram I. New cancer cases in France in 2015 attributable to infectious agents: a systematic review and meta-analysis. Eur J Epidemiol 2018; 33:263-274. [PMID: 29214413 DOI: 10.1007/s10654-017-0334-z] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2017] [Accepted: 11/20/2017] [Indexed: 12/31/2022]
Abstract
To provide an assessment of the burden of cancer in France in 2015 attributable to infectious agents. A systematic literature review in French representative cancer cases series was undertaken of the prevalence of infectious agents with the major associated cancer types. PubMed was searched for original studies published up to September 2016; random-effects meta-analyses were performed. Cancer incidence data were obtained from the French Cancer Registries Network, thereby allowing the calculation of national incidence estimates. The number of new cancer cases attributable to infectious agents was calculated using population-attributable fractions according to published methods. Of the 352,000 new cancer cases in France in 2015, 14,336 (4.1% of all new cancer cases) were attributable to infectious agents. The largest contributors were human papillomavirus (HPV) and Helicobacter pylori, responsible for 6333 and 4406 new cancer cases (1.8 and 1.3% of all new cancer cases) respectively. Infectious agents caused a non-negligible number of new cancer cases in France in 2015. Most of these cancers were preventable. The expansion of vaccination (i.e., for hepatitis B virus and HPV) and screen-and-treat programs (for HPV and hepatitis C virus, and possibly for H. pylori) could greatly reduce this cancer burden.
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Affiliation(s)
- Kevin David Shield
- Section of Cancer Surveillance, International Agency for Research on Cancer, 150 Cours Albert Thomas, 69372, Lyon Cedex 08, France.
| | - Claire Marant Micallef
- Section of Cancer Surveillance, International Agency for Research on Cancer, 150 Cours Albert Thomas, 69372, Lyon Cedex 08, France
| | - Catherine de Martel
- Infections and Cancer Epidemiology Group, International Agency for Research on Cancer, Lyon, France
| | - Isabelle Heard
- Prevention and Implementation Group, International Agency for Research on Cancer, Lyon, France
- Hospital Tenon, AP-HP, Paris, France
| | - Francis Megraud
- Laboratoire de Bactériologie, Hôpital Pellegrin, Bordeaux, France
| | - Martyn Plummer
- Infections and Cancer Epidemiology Group, International Agency for Research on Cancer, Lyon, France
| | - Jérôme Vignat
- Section of Cancer Surveillance, International Agency for Research on Cancer, 150 Cours Albert Thomas, 69372, Lyon Cedex 08, France
| | - Freddie Bray
- Section of Cancer Surveillance, International Agency for Research on Cancer, 150 Cours Albert Thomas, 69372, Lyon Cedex 08, France
| | - Isabelle Soerjomataram
- Section of Cancer Surveillance, International Agency for Research on Cancer, 150 Cours Albert Thomas, 69372, Lyon Cedex 08, France
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Haeggblom L, Ramqvist T, Tommasino M, Dalianis T, Näsman A. Time to change perspectives on HPV in oropharyngeal cancer. A systematic review of HPV prevalence per oropharyngeal sub-site the last 3 years. PAPILLOMAVIRUS RESEARCH (AMSTERDAM, NETHERLANDS) 2017; 4:1-11. [PMID: 29179862 PMCID: PMC5883233 DOI: 10.1016/j.pvr.2017.05.002] [Citation(s) in RCA: 75] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/07/2017] [Revised: 05/12/2017] [Accepted: 05/18/2017] [Indexed: 02/08/2023]
Abstract
OBJECTIVES Human papillomavirus (HPV) as a risk factor in oropharyngeal squamous cell carcinoma (OPSCC) is well established. However, accumulating data imply that the OPSCC concept is too unspecific with regard to HPV prevalence and clinical importance. To further study the role of HPV in OPSCC by sub-site, a systematic review and meta-analysis was performed. MATERIAL AND METHOD PubMed was searched and all studies reporting HPV data (p16/HPV DNA/RNA) in both "lymphoepithelial associated" (i.e. tonsillar and base of tongue cancer; TSCC and BOTSCC respectively) and "non-lymphoepithelial" ("other" OPSCC) OPSCC were included. Pooled odds ratios by HPV detection method were analysed using a random effects model. RESULTS In total, 58 unique patient cohorts were identified. Total HPV prevalence in TSCC/BOTSCC was 56%, 95%CI: 55-57% (59%, 95%CI: 58-60% for TSCC only) as compared to 19%, 95%CI: 17-20%, in "other" OPSCC. Significant association of HPV to TSCC/BOTSCC vs. "other" OPSCC was observed no matter HPV detection method used, but statistical homogeneity was only observed when studies using algorithm based HPV detection were pooled. CONCLUSION HPV prevalence differs markedly between OPSCC sub-sites and while the role of HPV in TSCC/BOTSCC is strong, the role in "other" OPSCC is more uncertain and needs further evaluation.
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Affiliation(s)
- Linnea Haeggblom
- Dept. of Oncology-Pathology, Karolinska Institutet, 171 76 Stockholm, Sweden
| | - Torbjörn Ramqvist
- Dept. of Oncology-Pathology, Karolinska Institutet, 171 76 Stockholm, Sweden
| | | | - Tina Dalianis
- Dept. of Oncology-Pathology, Karolinska Institutet, 171 76 Stockholm, Sweden
| | - Anders Näsman
- Dept. of Oncology-Pathology, Karolinska Institutet, 171 76 Stockholm, Sweden; Dept. of Clinical Pathology, Karolinska University Hospital, 171 76 Stockholm, Sweden.
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Albers AE, Qian X, Kaufmann AM, Coordes A. Meta analysis: HPV and p16 pattern determines survival in patients with HNSCC and identifies potential new biologic subtype. Sci Rep 2017; 7:16715. [PMID: 29196639 PMCID: PMC5711807 DOI: 10.1038/s41598-017-16918-w] [Citation(s) in RCA: 88] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2017] [Accepted: 11/19/2017] [Indexed: 02/07/2023] Open
Abstract
Consistent discrepancies in the p16/HPV-positivity have been observed in head and neck squamous cell carcinoma (HNSCC). It is therefore questionable, if all HPV+ and/or p16+ tested cancers are HPV-driven. Patients down-staged according to the HPV-dependant TNM are at risk for undertreatment and data in clinical trials may be skewed due to false patient inclusion. We performed a meta-analysis to classify clinical outcomes of the distinct subgroups with combined p16 and HPV detection. 25 out of 1677 publications fulfilled the inclusion criteria. The proportion of the subgroups was 35.6% for HPV+/p16+, 50.4% for HPV-/p16-, 6.7% for HPV-/p16+ and 7.3% for HPV+/P16-. The HPV+/p16+ subgroup had a significantly improved 5-year overall-survival (OS) and disease-free-survival in comparison to others both for HNSCC and oropharyngeal cancers. The 5-year OS of the HPV-/p16+ HNSCC was intermediate while HPV+/p16- and HPV-/p16- had the shortest survival outcomes. The clearly distinct survival of HPV-/p16+ cancers may characterize a new relevant HPV-independent subtype yet to be biologically characterized. The possibility also exists that in some HPV+/p16+ cancers HPV is an innocent bystander and p16 is independently positive. Therefore, in perspective, HPV-testing should distinguish between bystander HPV and truly HPV-driven cancers to avoid potential undertreatment in HPV+ but non-HPV-driven HNSCC.
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Affiliation(s)
- Andreas E Albers
- Department of Otorhinolaryngology, Head and Neck Surgery, Berlin Institute of Health, Charite - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Campus Benjamin Franklin, Berlin, Germany.
| | - Xu Qian
- Department of Otorhinolaryngology, Head and Neck Surgery, Berlin Institute of Health, Charite - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Campus Benjamin Franklin, Berlin, Germany
| | - Andreas M Kaufmann
- Clinic for Gynecology, Charité - Berlin Institute of Health, Charite - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Campus Benjamin Franklin, Berlin, Germany
| | - Annekatrin Coordes
- Department of Otorhinolaryngology, Head and Neck Surgery, Berlin Institute of Health, Charite - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Campus Benjamin Franklin, Berlin, Germany
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Jéhannin-Ligier K, Belot A, Guizard AV, Bossard N, Launoy G, Uhry Z. Incidence trends for potentially human papillomavirus-related and -unrelated head and neck cancers in France using population-based cancer registries data: 1980-2012. Int J Cancer 2017; 140:2032-2039. [PMID: 28164282 PMCID: PMC6166780 DOI: 10.1002/ijc.30631] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2016] [Revised: 01/20/2017] [Accepted: 01/26/2017] [Indexed: 12/30/2022]
Abstract
Human papillomavirus (HPV) has been recently recognised as a carcinogenic factor for a subset of head and neck cancers (HNC). In Europe, France has one of the highest incidence rates of HNC. The aim of this study is to explore changes in HNC incidence in France, potentially in relation with infection by HPV. HNC were classified into two anatomical groups: potentially HPV-related and HPV-unrelated. Trends over the period 1980-2012 were analysed by an age-period-cohort model based on data from eleven French cancer registries. Among men, the age-standardised incidence rate (ASR) of HNC decreased in both groups, but less so for HPV-related sites as compared to unrelated sites, especially in recent years (annual percentage change [APC] over the period 2005-2012: -3.5% vs. -5.4%). Among women, the ASR increased in both groups, but more rapidly for HPV-related as compared to unrelated sites (APC over the period 2005-2012: +1.9% vs. -0.4%). This preferential growth of HPV-related versus unrelated HNC was observed in the cohorts born from 1930 to 1935. The differences in trends between possible HPV-related and HPV-unrelated sites suggest an increasing incidence of HNC due to HPV infection. The difference was less marked in men as compared to women, most likely because of a higher contamination in the HPV-related group by cancers due to tobacco or alcohol consumption. The pattern observed is consistent with observations made in other countries, with studies of HPV prevalence in HNC and the evolution of sexual behaviour in France.
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Affiliation(s)
- Karine Jéhannin-Ligier
- Registre Général des Cancers de Lille et de sa Région, Centre de Référence Régional en Cancérologie, CHRU de LILLE, Hôpital Calmette - Pavillon Breton, Boulevard du Professeur Jules Leclercq, 59037 LILLE cedex, France
| | - Aurélien Belot
- Service de biostatistiques des Hospices civils de Lyon, Centre Hospitalier Lyon Sud, Pierre Benite, France
- Université de Lyon, Lyon, France
- Université de Lyon 1, Villeurbanne, France
- CNRS UMR 5558, Laboratoire de Biométrie et de Biologie Evolutive, Equipe Biostatistique-Santé, Villeurbanne, France
| | - Anne-Valérie Guizard
- Registre Général des Tumeurs du Calvados, U1086 INSERM, UCBN, Centre François Baclesse, Caen, France
| | - Nadine Bossard
- Service de biostatistiques des Hospices civils de Lyon, Centre Hospitalier Lyon Sud, Pierre Benite, France
- Université de Lyon, Lyon, France
- Université de Lyon 1, Villeurbanne, France
- CNRS UMR 5558, Laboratoire de Biométrie et de Biologie Evolutive, Equipe Biostatistique-Santé, Villeurbanne, France
| | - Guy Launoy
- U1086 Inserm, UCBN, UFR médecine Caen, Pôle de Recherche CHRU de Caen, Centre François Baclesse, Caen, France
| | - Zoé Uhry
- Service de biostatistiques des Hospices civils de Lyon, Centre Hospitalier Lyon Sud, Pierre Benite, France
- Santé Publique France, Saint-Maurice, France
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Smith EA, Kumar B, Komurov K, Smith SM, Brown NV, Zhao S, Kumar P, Teknos TN, Wells SI. DEK associates with tumor stage and outcome in HPV16 positive oropharyngeal squamous cell carcinoma. Oncotarget 2017; 8:23414-23426. [PMID: 28423581 PMCID: PMC5410314 DOI: 10.18632/oncotarget.15582] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2016] [Accepted: 02/12/2017] [Indexed: 01/25/2023] Open
Abstract
Oropharyngeal squamous cell carcinomas (OPSCC) are common, have poor outcomes, and comprise two biologically and clinically distinct diseases. While OPSCC that arise from human papillomavirus infections (HPV+) have better overall survival than their HPV- counterparts, the incidence of HPV+ OPSCC is increasing dramatically, affecting younger individuals which are often left with life-long co-morbidities from aggressive treatment. To identify patients which do poorly versus those who might benefit from milder regimens, risk-stratifying biomarkers are now needed within this population. One potential marker is the DEK oncoprotein, whose transcriptional upregulation in most malignancies is associated with chemotherapy resistance, advanced tumor stage, and worse outcomes. Herein, a retrospective case study was performed on DEK protein expression in therapy-naïve surgical resections from 194 OPSCC patients. We found that DEK was associated with advanced tumor stage, increased hazard of death, and interleukin IL6 expression in HPV16+ disease. Surprisingly, DEK levels in HPV16- OPSCC were not associated with advanced tumor stage or increased hazard of death. Overall, these findings mark HPV16- OPSCC as an exceptional malignancy were DEK expression does not correlate with outcome, and support the potential prognostic utility of DEK to identify aggressive HPV16+ disease.
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Affiliation(s)
- Eric A. Smith
- Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229, USA
| | - Bhavna Kumar
- Department of Otolaryngology–Head and Neck Surgery, The Ohio State University, Columbus, OH, 43210, USA
- The Ohio State University, Comprehensive Cancer Center, Columbus, OH 43210, USA
| | - Kakajan Komurov
- Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229, USA
| | - Stephen M. Smith
- Department of Pathology, The Ohio State University, Columbus, OH, 43210, USA
| | - Nicole V. Brown
- Center for Biostatistics, The Ohio State University, Columbus, OH, 43210, USA
| | - Songzhu Zhao
- Center for Biostatistics, The Ohio State University, Columbus, OH, 43210, USA
| | - Pawan Kumar
- Department of Otolaryngology–Head and Neck Surgery, The Ohio State University, Columbus, OH, 43210, USA
- The Ohio State University, Comprehensive Cancer Center, Columbus, OH 43210, USA
| | - Theodoros N. Teknos
- Department of Otolaryngology–Head and Neck Surgery, The Ohio State University, Columbus, OH, 43210, USA
- The Ohio State University, Comprehensive Cancer Center, Columbus, OH 43210, USA
| | - Susanne I. Wells
- Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229, USA
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Swangphon P, Pientong C, Burassakarn A, Vatanasapt P, Kleebkaow P, Patarapadungkit N, Treebupachatsakul T, Promthet S, Kongyingyoes B, Ekalaksananan T. Methylation Status of P16Ink4a in Human Papillomavirus-Associated Cancer of Oral Cavity and Oropharynx in Northeastern Thailand. Asian Pac J Cancer Prev 2017; 18:699-705. [PMID: 28440978 PMCID: PMC5464487 DOI: 10.22034/apjcp.2017.18.3.699] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
Background: Over-expression of p16INK4a protein is a biomarker for human papillomavirus (HPV)-associated cervical cancer. However, absence of p16INK4a protein expression in HPV-associated cancer of the oral cavity and oropharynx has been reported. Among a number of possible reasons for this is methylation, which is frequently noted in the promoter region of p16INK4a and is associated with silencing of the gene and disease severity. Methods: We investigated the relationships between p16INK4a protein expression, HPV infection and methylation status of the p16INK4a promoter in cancers of the oral cavity and oropharynx. Fifty-three formalin-fixed paraffin-embedded (FFPE) cancer tissue samples from the oral cavity (49 cases) and oropharynx (4 cases) were studied. P16INK4a protein expression was determined using immunohistochemical staining (IHC). Additional oral tissues lacking squamous intraepithelial lesions (SILs), and cervical tissues with high-level SILs, were used as negative and positive controls, respectively. High-risk HPV infection was detected using HPV E6/E7 mRNA in situ hybridization. Methylation status of the p16INK4a promoter was investigated using sodium bisulfite treatment and methylation-specific PCR (MS-PCR). Results: HPV infection was found in 40.8% (20/49) and 50.0% (2/4) of oral cavity and oropharynx cancers, respectively. Promoter methylation of p16INK4a occurred in 73.6 % of all cases and differed significantly in frequency between HPV-positive (90.9%, 20/22) and HPV-negative (61.3%, 19/31) samples. Expression of p16INK4a was found in 35.8% (19/53) and commonly detected in samples with p16INK4a unmethylation (79.5%). Interestingly, the silencing of p16INK4a (64.2%, 34/53) was significantly associated with methylation status (91.2%, 31/34), especially in HPV-infected samples in which the p16INK4a promoter was methylated (52.9%, 18/34). Conclusions: This result demonstrated high frequency of p16INK4a promoter methylation status in HPV-associated HNSCC subsets that could influence the silent p16INK4a expression and might promote disease severity.
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Affiliation(s)
- Piyawut Swangphon
- Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
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HPV16 detection by qPCR method in relation to quantity and quality of DNA extracted from archival formalin fixed and paraffin embedded head and neck cancer tissues by three commercially available kits. J Virol Methods 2016; 236:157-163. [DOI: 10.1016/j.jviromet.2016.07.021] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2016] [Revised: 07/19/2016] [Accepted: 07/22/2016] [Indexed: 11/20/2022]
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Dunkel J, Vaittinen S, Koivunen P, Laranne J, Mäkinen MJ, Tommola S, Irjala H. Tumoral Expression of CD44 and HIF1α Predict Stage I Oral Cavity Squamous Cell Carcinoma Outcome. Laryngoscope Investig Otolaryngol 2016; 1:6-12. [PMID: 28894797 DOI: 10.1002/lio2.3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/09/2015] [Indexed: 12/22/2022] Open
Abstract
OBJECTIVES/HYPOTHESIS No biomarkers are used to estimate the prognosis in oral cavity squamous cell carcinoma (OSCC). In our previously published work, we have reported the prognostic value of CD44 and hypoxia inducible factor (HIF)-1α in patients with stage I disease. STUDY DESIGN In this study, we tested our previous observations in a larger cohort. We also studied the predictive value of common lymphatic endothelial and vascular endothelial receptor (CLEVER)-1 in this material. METHODS CD44, HIF1α, and CLEVER-1 were immunohistochemically analyzed in paraffin-embedded tissue material of stage I OSCC patients treated at three Finnish university hospitals. Microscopy results were correlated with OSCC outcome. RESULTS As in our pilot study, the CD44lowHIF1αhigh signature was associated with poorer disease-free survival. Clear correlations between CLEVER-1 expression and clinical outcome were not evident. CONCLUSION Our results suggest that immunohistochemistry of CD44 and HIF1α may be useful in identification of patients with poor prognoses. These parameters could be used to select the optimal treatment modalities for stage I OSCC patients. LEVEL OF EVIDENCE 2b.
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Affiliation(s)
- Johannes Dunkel
- Medicity Research Laboratory and Turku Doctoral Programme of Molecular Medicine University of Turku
| | - Samuli Vaittinen
- the Department of Pathology University of Turku and Turku University Hospital Turku
| | - Petri Koivunen
- the Research Center for Otorhinolaryngology and Ophthalmology, University of Oulu and Department of Otorhinolaryngology and Medical Research Center Oulu, Oulu University Hospital
| | - Jussi Laranne
- the Department of Otorhinolaryngology Head and Neck Surgery Tampere University Hospital
| | - Markus J Mäkinen
- the Department of Pathologyand Medical Research Center Oulu, Oulu University Hospital and University of Oulu Oulu
| | - Satu Tommola
- the Department of Pathology University of Tampere and Tampere University Hospital Tampere Finland
| | - Heikki Irjala
- the Department of Otorhinolaryngology Head and Neck Surgery Turku University Hospital
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de Matos LL, Miranda GA, Cernea CR. Prevalence of oral and oropharyngeal human papillomavirus infection in Brazilian population studies: a systematic review. Braz J Otorhinolaryngol 2015; 81:554-67. [PMID: 26248966 PMCID: PMC9449068 DOI: 10.1016/j.bjorl.2015.04.001] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2015] [Revised: 04/21/2015] [Accepted: 04/22/2015] [Indexed: 11/25/2022] Open
Abstract
Introduction Human papillomavirus has been associated with head and neck squamous cell carcinoma. However, there is no conclusive evidence on the prevalence of oral or pharyngeal infection by human papillomavirus in the Brazilian population. Objective To determine the rate of human papillomavirus infection in the Brazilian population. Methods Systematic review of published articles. Medline, The Cochrane Library, Embase, Lilacs (Latin American and Caribbean Health Sciences) and Scielo electronic databases were searched. The search included published articles up to December 2014 in Portuguese, Spanish and English. A wide search strategy was employed in order to avoid publication biases and to assess studies dealing only with oral and/or oropharyngeal human papillomavirus infections in the Brazilian population. Results The 42 selected articles enrolled 4066 patients. It was observed that oral or oropharyngeal human papillomavirus infections were identified in 738 patients (18.2%; IC 95 17.6–18.8), varying between 0.0% and 91.9%. The prevalences of oral or oropharyngeal human papillomavirus infections were respectively 6.2%, 44.6%, 44.4%, 27.4%, 38.5% and 11.9% for healthy people, those with benign oral lesions, pre-malignant lesions, oral or oropharyngeal squamous cell carcinoma, risk groups (patients with genital human papillomavirus lesions or infected partners) and immunocompromised patients. The risk of human papillomavirus infection was estimated for each subgroup and it was evident that, when compared to the healthy population, the risk of human papillomavirus infection was approximately 1.5–9.0 times higher, especially in patients with an immunodeficiency, oral lesions and squamous cell carcinoma. The rates of the most well-known oncogenic types (human papillomavirus 16 and/or 18) also show this increased risk. Conclusions Globally, the Brazilian healthy population has a very low oral human papillomavirus infection rate. Other groups, such as at-risk patients or their partners, immunocompromised patients, people with oral lesions and patients with oral cavity or oropharyngeal squamous cell carcinoma have a high risk of human papillomavirus infection.
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Coordes A, Lenz K, Qian X, Lenarz M, Kaufmann AM, Albers AE. Meta-analysis of survival in patients with HNSCC discriminates risk depending on combined HPV and p16 status. Eur Arch Otorhinolaryngol 2015; 273:2157-69. [DOI: 10.1007/s00405-015-3728-0] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2015] [Accepted: 07/14/2015] [Indexed: 12/23/2022]
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Mesía R, Henke M, Fortin A, Minn H, Yunes Ancona AC, Cmelak A, Markowitz AB, Hotte SJ, Singh S, Chan ATC, Merlano MC, Skladowski K, Zhang A, Oliner KS, VanderWalde A, Giralt J. Chemoradiotherapy with or without panitumumab in patients with unresected, locally advanced squamous-cell carcinoma of the head and neck (CONCERT-1): a randomised, controlled, open-label phase 2 trial. Lancet Oncol 2015; 16:208-20. [PMID: 25596660 DOI: 10.1016/s1470-2045(14)71198-2] [Citation(s) in RCA: 110] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
BACKGROUND Panitumumab is a fully human monoclonal antibody that targets EGFR. We aimed to compare chemoradiotherapy plus panitumumab with chemoradiotherapy alone in patients with unresected, locally advanced squamous-cell carcinoma of the head and neck. METHODS In this international, open-label, randomised, controlled, phase 2 trial, we recruited patients with locally advanced squamous-cell carcinoma of the head and neck from 41 sites in nine countries worldwide. Patients aged 18 years and older with stage III, IVa, or IVb, previously untreated, measurable (≥ 10 mm for at least one dimension), locally advanced squamous-cell carcinoma of the head and neck (non-nasopharygeal) and an Eastern Cooperative Oncology Group performance status of 0-1 were randomly assigned (2:3) by an independent vendor to open-label chemoradiotherapy (three cycles of cisplatin 100 mg/m(2)) or panitumumab plus chemoradiotherapy (three cycles of intravenous panitumumab 9.0 mg/kg every 3 weeks plus cisplatin 75 mg/m(2)) using stratified randomisation with a block size of five. All patients received 70 Gy to gross tumour and 50 Gy to areas at risk for subclinical disease with standard fractionation. The primary endpoint was local-regional control at 2 years, analysed in all randomised patients who received at least one dose of their assigned protocol-specific treatment (chemotherapy, radiation, or panitumumab). The trial is closed and this is the final analysis. This trial is registered with ClinicalTrials.gov, number NCT00500760. FINDINGS Between Oct 26, 2007, and March 26, 2009, 153 patients were enrolled and 150 received treatment (63 in the chemoradiotherapy group and 87 in the panitumumab plus chemoradiotherapy group). Local-regional control at 2 years was 68% (95% CI 54-78) in the chemoradiotherapy group and 61% (50-71) in the panitumumab plus chemoradiotherapy group. The most frequent grade 3-4 adverse events were dysphagia (17 [27%] of 63 patients in the chemoradiotherapy group vs 35 [40%] of 87 in the panitumumab plus chemoradiotherapy group), mucosal inflammation (15 [24%] vs 48 [55%]), and radiation skin injury (eight [13%] vs 27 [31%]). Serious adverse events were reported in 20 (32%) of 63 patients in the chemoradiotherapy group and in 37 (43%) of 87 patients in the panitumumab plus chemoradiotherapy group. INTERPRETATION In patients with locally advanced squamous-cell carcinoma of the head and neck, the addition of panitumumab to standard fractionation radiotherapy and cisplatin did not confer any benefit, and the role of EGFR inhibition in these patients needs to be reassessed. FUNDING Amgen.
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Affiliation(s)
- Ricard Mesía
- Institut Catala d'Oncologia (ICO)-L'Hospitalet, Barcelona, Spain.
| | - Michael Henke
- Strahlenheilkunde Universitätsklinikum, Freiburg, Germany
| | - Andre Fortin
- Centre Hospitalier Universitaire de Quebec-Hotel-Dieu de Quebec, Quebec, QC, Canada
| | - Heikki Minn
- Turku University Hospital Department of Oncology and Radiotherapy, Turku, Finland
| | | | - Anthony Cmelak
- Vanderbilt University Medical Center, Nashville, TN, USA
| | | | | | - Simron Singh
- Sunnybrook Health Sciences Centre-Odette Cancer Centre, Toronto, ON, Canada
| | - Anthony T C Chan
- State Key Laboratory in Oncology in South China, The Sir YK Pao Centre for Cancer, The Chinese University of Hong Kong, Hong Kong, China
| | | | | | | | | | | | - Jordi Giralt
- Hospital Vall d'Hebron, Barcelona, Spain; Universitat Autònoma de Barcelona, Bellaterra, Spain
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Garnaes E, Kiss K, Andersen L, Therkildsen MH, Franzmann MB, Filtenborg-Barnkob B, Hoegdall E, Krenk L, Josiassen M, Lajer CB, Specht L, Frederiksen K, Friis-Hansen L, Nielsen FC, Kjaer SK, Norrild B, von Buchwald C. A high and increasing HPV prevalence in tonsillar cancers in Eastern Denmark, 2000-2010: The largest registry-based study to date. Int J Cancer 2014; 136:2196-203. [DOI: 10.1002/ijc.29254] [Citation(s) in RCA: 89] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2014] [Revised: 08/15/2014] [Accepted: 09/09/2014] [Indexed: 12/25/2022]
Affiliation(s)
- Emilie Garnaes
- Department of Otorhinolaryngology, Head and Neck Surgery and Audiology; Rigshospitalet, University of Copenhagen; Copenhagen Denmark
| | - Katalin Kiss
- Department of Pathology; Rigshospitalet, University of Copenhagen; Copenhagen Denmark
| | - Luise Andersen
- Department of Pathology; Roskilde Hospital; Roskilde Denmark
| | | | | | | | | | - Lene Krenk
- Department of Otorhinolaryngology, Head and Neck Surgery and Audiology; Rigshospitalet, University of Copenhagen; Copenhagen Denmark
| | - Michael Josiassen
- Department of Otorhinolaryngology, Head and Neck Surgery and Audiology; Rigshospitalet, University of Copenhagen; Copenhagen Denmark
| | - Christel B. Lajer
- Department of Otorhinolaryngology, Head and Neck Surgery and Audiology; Rigshospitalet, University of Copenhagen; Copenhagen Denmark
| | - Lena Specht
- Department of Oncology; Rigshospitalet, University of Copenhagen; Copenhagen Denmark
| | - Kirsten Frederiksen
- Department of Statistics, Bioinformatics and Registry; Danish Cancer Society Research Center; Copenhagen Denmark
| | - Lennart Friis-Hansen
- Center for Genomic Medicine, Rigshospitalet, University of Copenhagen; Copenhagen Denmark
| | - Finn C. Nielsen
- Center for Genomic Medicine, Rigshospitalet, University of Copenhagen; Copenhagen Denmark
| | - Susanne K. Kjaer
- Department of Virus, Lifestyle and Genes; Danish Cancer Society Research Center and Department of Gynecology, Rigshospitalet, University of Copenhagen; Copenhagen Denmark
| | - Bodil Norrild
- Institute of Cellular and Molecular Medicine, Panum Institute, University of Copenhagen; Copenhagen Denmark
| | - Christian von Buchwald
- Department of Otorhinolaryngology, Head and Neck Surgery and Audiology; Rigshospitalet, University of Copenhagen; Copenhagen Denmark
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Woods RSR, O’Regan EM, Kennedy S, Martin C, O’Leary JJ, Timon C. Role of human papillomavirus in oropharyngeal squamous cell carcinoma: A review. World J Clin Cases 2014; 2:172-193. [PMID: 24945004 PMCID: PMC4061306 DOI: 10.12998/wjcc.v2.i6.172] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2014] [Revised: 04/21/2014] [Accepted: 05/19/2014] [Indexed: 02/05/2023] Open
Abstract
Human papillomavirus (HPV) has been implicated in the pathogenesis of a subset of oropharyngeal squamous cell carcinoma. As a result, traditional paradigms in relation to the management of head and neck squamous cell carcinoma have been changing. Research into HPV-related oropharyngeal squamous cell carcinoma is rapidly expanding, however many molecular pathological and clinical aspects of the role of HPV remain uncertain and are the subject of ongoing investigation. A detailed search of the literature pertaining to HPV-related oropharyngeal squamous cell carcinoma was performed and information on the topic was gathered. In this article, we present an extensive review of the current literature on the role of HPV in oropharyngeal squamous cell carcinoma, particularly in relation to epidemiology, risk factors, carcinogenesis, biomarkers and clinical implications. HPV has been established as a causative agent in oropharyngeal squamous cell carcinoma and biologically active HPV can act as a prognosticator with better overall survival than HPV-negative tumours. A distinct group of younger patients with limited tobacco and alcohol exposure have emerged as characteristic of this HPV-related subset of squamous cell carcinoma of the head and neck. However, the exact molecular mechanisms of carcinogenesis are not completely understood and further studies are needed to assist development of optimal prevention and treatment modalities.
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Lacroix L, Post SF, Valent A, Melkane AE, Vielh P, Egile C, Castell C, Larois C, Micallef S, Saulnier P, Goulaouic H, Lefebvre AM, Temam S. MET genetic abnormalities unreliable for patient selection for therapeutic intervention in oropharyngeal squamous cell carcinoma. PLoS One 2014; 9:e84319. [PMID: 24465403 PMCID: PMC3894941 DOI: 10.1371/journal.pone.0084319] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2013] [Accepted: 11/14/2013] [Indexed: 11/19/2022] Open
Abstract
Background Identification of MET genetic alteration, mutation, or amplification in oropharyngeal squamous cell carcinoma (OPSCC) could lead to development of MET selective kinase inhibitors. The aim of this study was to assess the frequency and prognostic value of MET gene mutation, amplification, and protein expression in primary OPSCC. Methods A retrospective chart review was conducted of patients treated for single primary OPSCC between January 2007 and December 2009. Pre-treatment OPSCC tissue samples were analyzed for MET mutations, gene amplification, and overexpression using Sanger sequencing, FISH analysis, and immunohistochemistry respectively. Univariate and multivariate analyses were used to analyze correlations between molecular abnormalities and patient survival. Results 143 patients were included in this study. Six cases (4%) were identified that had a genetic variation, but previously described mutations such as p.Tyr1235Asp (Y1235D) or p.Tyr1230Cys (Y1230C) were not detected. There were 15 high polysomy cases, and only 3 cases met the criteria for true MET amplification, with ≥10% amplified cells per case. Immunohistochemistry evaluation showed 43% of cases were c-MET negative and in 57% c-MET was observed at the tumor cell level. Multivariate analysis showed no significant association between MET mutation, amplification, or expression and survival. Conclusions Our study shows a low frequency of MET mutations and amplification in this cohort of OPSCC. There was no significant correlation between MET mutations, amplification, or expression and patient survival. These results suggest that patient selection based on these MET genetic abnormalities may not be a reliable strategy for therapeutic intervention in OPSCC.
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Affiliation(s)
- Ludovic Lacroix
- Department of Medical Biology and Pathology, Institut Gustave Roussy, Villejuif, France
- Translational Research Laboratory and Biobank, Institut Gustave Roussy, Villejuif, France
| | - Sophie F. Post
- Department of Head and Neck Surgical Oncology, Institut Gustave Roussy, Villejuif, France
- Department of Plastic Surgery, University Medical Centre Groningen, Groningen, The Netherlands
| | - Alexander Valent
- Department of Medical Biology and Pathology, Institut Gustave Roussy, Villejuif, France
- Translational Research Laboratory and Biobank, Institut Gustave Roussy, Villejuif, France
| | - Antoine E. Melkane
- Department of Head and Neck Surgical Oncology, Institut Gustave Roussy, Villejuif, France
| | - Philippe Vielh
- Department of Medical Biology and Pathology, Institut Gustave Roussy, Villejuif, France
- Translational Research Laboratory and Biobank, Institut Gustave Roussy, Villejuif, France
| | | | | | - Christelle Larois
- Department of Biologics Scientific Core Platform (BioSCP), Sanofi, Vitry-sur-Seine, France
| | - Sandrine Micallef
- Department of Scientific Core Platform Clinical and Scientific Operations (SCP CSO), Sanofi, Vitry-sur-Seine, France
| | - Patrick Saulnier
- Translational Research Laboratory and Biobank, Institut Gustave Roussy, Villejuif, France
| | | | - Anne-Marie Lefebvre
- Department of Biologics Scientific Core Platform (BioSCP), Sanofi, Vitry-sur-Seine, France
| | - Stéphane Temam
- Department of Head and Neck Surgical Oncology, Institut Gustave Roussy, Villejuif, France
- * E-mail:
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Melkane AE, Mirghani H, Aupérin A, Saulnier P, Lacroix L, Vielh P, Casiraghi O, Griscelli F, Temam S. HPV-related oropharyngeal squamous cell carcinomas: a comparison between three diagnostic approaches. Am J Otolaryngol 2014; 35:25-32. [PMID: 24112760 DOI: 10.1016/j.amjoto.2013.08.007] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2013] [Accepted: 08/03/2013] [Indexed: 01/28/2023]
Abstract
PURPOSE HPV-related oropharyngeal squamous cell carcinomas clearly represent a growing entity in the head and neck with distinct carcinogenesis, clinico-pathological presentation and survival profile. We aimed to compare the HPV prevalence rates and clinico-pathological correlations obtained with three distinct commonly used HPV detection methods. MATERIALS AND METHODS p16-immunohistochemistry (IHC), HPV DNA viral load by real-time PCR (qPCR), and HPV genotyping by a reverse hybridization-based line probe assay (INNO-LiPA) were performed on pretreatment formalin-fixed paraffin-embedded tumor samples from 46 patients treated for single primary oropharyngeal carcinomas. RESULTS Twenty-eight patients (61%) had a p16 overexpression in IHC. Twenty-nine patients (63%) harbored HPV DNA on qPCR. Thirty-four patients (74%) harbored HPV DNA on INNO-LiPA. The concordance analysis revealed a good agreement between both HPV DNA detection methods (κ=0.65); when both tests were positive, the depicted HPV subtypes were always concordant (HPV16 in 27 cases, HPV18 in 1 case). Agreement was moderate between IHC and qPCR (κ=0.59) and fair between IHC and INNO-LiPA (κ=0.22). CONCLUSIONS Certain highly sensitive methods are able to detect the mere presence of HPV without any carcinogenetic involvement while other more specific tests provide proof of viral transcriptional activity and thus evidence of clinically relevant infections. The use of a stepwise approach allows reducing false positives; p16-immunostaining seems to be an excellent screening test and in situ hybridization may overcome some of the PCR limitations.
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