HPV and head and neck cancer

Head and neck cancer is frequent worldwide and oropharyngeal locations are presently sharply on the increase, in relation with an increasing incidence of oropharyngeal infection by oncogenic type-16 human papillomavirus (HPV). The clinical and biologic profile of these patients is distinct from that of other oropharyngeal carcinoma patients, with earlier onset, cystic cervical nodes and basaloid carcinoma histopathology. Detection of intratumoral viral DNA is essential to confirm the role of HPV, and E6/E7 mRNA expression is the most relevant indicator for stratification. Several methods can reveal intratumoral oncogenic HPV DNA, but PCR with hybridization is the most sensitive and most widely used. According to several reports, prognosis in terms of survival and locoregional control is better in HPV-positive oropharyngeal carcinoma than in oropharyngeal carcinoma associated with smoking and alcohol consumption. The future lies in vaccination, but further studies will determine whether the rate of oropharyngeal carcinoma falls in women vaccinated against cervical cancer.     

Racial disparities in Human Papillomavirus (HPV) associated head and neck cancer

Purpose

Poorer survival from head and neck squamous cell carcinoma (HNSCC) in African Americans (AA) may be due to disparity in the prevalence of Human Papillomavirus (HPV) but earlier studies often failed to control other etiological factors. We aimed to elucidate whether racial disparities in HPV prevalence and overall survival were due to confounding from smoking or alcohol use.

Materials and methods

385 patients with SCC of the mouth, pharynx, nose, or larynx who had surgical resection at Wayne State University affiliated hospitals were identified through a population-based cancer registry. Formalin fixed paraffin embedded tissue blocks were used to determine the presence of HPV DNA and its genotype using a sensitive broad-spectrum PCR technique. Patients’ demographics, tumor characteristics and vital status were obtained through record linkage with the registry data and smoking and alcohol information was abstracted from medical record. Cox’s proportional hazard model and unconditional logistic regression models were employed to analyze the overall survival and tumor HPV-positivity, respectively.

Results

HPV positivity in oropharyngeal cancer was substantially lower in AA than in other racial groups (odds ratio 0.14, 95% confidence interval (CI) 0.05–0.37) and adjustment for smoking or alcohol did not change this association. However, a significantly increased hazard ratio of death in AA oropharyngeal cancer patients (univariable hazard ratio (HR) 2.55, 95% CI 1.42–4.59) decreased to almost unity (HR 1.49, 95% CI 0.75–2.93) after adjustment for HPV and smoking.

Conclusions

Lower HPV prevalence in AA largely accounts for their poorer survival from oropharyngeal cancer, but not other HNSSC.     

HPV vaccination in head and neck HPV-related pathologies

Recent data demonstrate that human papilloma virus (HPV) plays a role in pathologies other than ano-genital cancers, specifically head and neck malignancies, and non-cancerous conditions such as recurrent respiratory papillomatosis (RRP). High-risk HPV16 and 18, and low risk HPV6 and 11 play the main role in HPV-related pathologies. As more and more information about the role of HPV infection in non-cervical diseases is amassed, additional questions about whether prophylactic HPV vaccines will effectively prevent these conditions are raised. HPV vaccination programs for the cervical pathology are being implemented worldwide. In the United States, the US Food and Drug Administration (FDA) approved the quadrivalent HPV vaccine for girls in 2006 and for boys in 2011. These vaccination programs were aimed at the genital, HPV-related lesions, and there was not much recognition at that time of how HPV vaccination programs might affect oral HPV infection, which is a risk factor for the development of HPV-related head and neck cancers. Vaccination has proved to be a successful policy, and an extant recommendation is aimed at preventing HPV and associated cervical and other anogenital cancers with the routine use of HPV vaccines for males and females. However, HPV vaccines are presently not recommended for preventing oropharyngeal cancer (OPC), although they have been shown to be highly effective against the HPV strains that are most commonly found in the oropharynx. This review is aimed at presenting the evidence-based knowledge concerning HPV vaccination and highlighting the trials and strategies for vaccine administration in HPV-dependent head and neck pathologies.     

EBV and not HPV sensitizes tobacco-associated head and neck cancer cell line FaDu to radiotherapy

Conclusion EBV radiosensitized the p53 mutant tobacco associated head and neck cell line, FaDu.

Objectives In the head and neck, HPV is a major risk factor associated with tonsil and base of tongue cancers, while a majority of undifferentiated nasopharyngeal cancers are positive for EBV. Clinically, head and neck tumors positive for HPV or EBV are more radiosensitive than tumors associated with tobacco and alcohol. This study aimed to evaluate whether viral infections can sensitize tobacco-associated head and neck squamous cell carcinoma cell line that harbors multiple mutations, especially TP53, to radiotherapy. Method Four FaDu cell lines (vector control – FaDu-DN; FaDu expressing HPV16 E6/E7 – FaDu-HPV; FaDu infected with EBV – FaDu-EBV; and FaDu-HPV infected with EBV – FaDu-HE) were evaluated for their radiation sensitivity using clonogenic assay. Cell cycle, protein expression, apoptosis, and cellular senescence were analyzed.

Results FaDu-EBV and FaDu-HE exhibited significantly increased radiosensitivity in comparison with the control cell line. Radiation-induced cell cycle arrest was altered in all cell lines expressing viral genes. The observed distribution of cells at G1 and S phases was associated with a significant increase in expression of p21 protein along with decreased levels of pAKT/AKT and pERK/ERK ratio (p?p?相似文献   

Impact of HPV infection on the clinical outcome of p-CAIR trial in head and neck cancer

The purpose of the study was to analyse the influence of HPV infection on the outcome of a randomized clinical trial of conventional (CF) versus 7-days-a-week postoperative radiotherapy (p-CAIR) for squamous cell cancer of the head and neck (SCCHN). Between 2001 and 2004, 279 patients with high-risk SCC of the larynx or cancer of the oral cavity/oropharynx were randomized to receive 63 Gy in fractions of 1.8 Gy given 5 days a week or 7 days a week (Radiother Oncol 87:155–163, 2008). The presence of HPV DNA in 131 archival paraffin blocks was assessed with multiplex quantitative real-time PCR using five consensus primers for the conservative L1 region and molecular beacon probes targeting 14 high-risk HPV subtypes. Following the RT-PCR procedure, we could determine the presence and type of HPV16, HPV18 and the other 12 less frequent oncogenic subtypes. Out of 131 samples, 9 were positive for HPV infection (6.9%), all of them with HPV16 subtype. None of the 65 laryngeal tumours was HPV positive. The 5-year LRC in HPV-positive patients was 100%, compared to 58% in the HPV-negative group (p = 0.02, log-rank test). Amongst 122 patients with HPV-negative tumours, 5-year LRC was 50.3% in p-CF versus 65.2 in p-CAIR (p = 0.37). HPV infection was associated with low expression of EGFR and cyclin D. This study demonstrates a favourable outcome for HPV-positive patients with SCCHN treated with postoperative radiotherapy. While considering the small number of HPV+ tumours, the data set can be considered as hypothesis generating only, the outcome raises new questions on the necessity of aggressive postoperative treatment in HPV+ patients.     

Papillomavirus and head and neck cancer

Tobacco and alcohol consumption are the main risk factors for head and neck cancers. Papillomavirus (HPV) infection was recently associated with the development of malignant tumors of the oropharynx, according to molecular and biological arguments. We describe the oncogenic mechanisms of HPV infections, the epidemiological and clinical aspects of associated head and neck cancers, their prognosis, and issues of specific therapeutic strategies.     

Oncogenes in head and neck cancer

Primary head and neck squamous cell carcinomas from 58 patients were analyzed for the presence of alterations in the K-ras, raf, and erb-B oncogenes. Analysis of 17 fresh tumor specimens using sequence analysis of target sequences amplified by the polymerase chain reaction showed no evidence of mutations in the K-ras oncogene. Thirty fresh tumor specimens were analyzed for the presence of raf gene activation using Southern blot analysis. Under these conditions, no mutations in the c-raf oncogene were detected. In this study, 6 (13%) of the 47 tumors studied displayed epidermal growth factor receptor (EGFR) gene amplification and/or gene rearrangement. Overexpression of the erb-B gene was observed in 18 (67%) of the 27 head and neck tumors studied. Those patients expressing high levels of EGFR or showing EGFR amplification had tumors that were clinically more advanced. These data suggest that amplification and over-expression of the EGFR gene may be a useful diagnostic and prognostic marker in head and neck squamous cell carcinomas.     

Chemotherapy of head and neck cancer

Squamous cell cancer of the head and neck accounts for five per cent of cases of cancer in the United States. Both the poor overall survival in cancer treated by surgery and radiation and the severe deformities associated with treatment have led to the investigation of adjuvant induction chemotherapy for high-risk patients. This article reviews the role of chemotherapy in the care of these patients.     

Epidemiology of head and neck cancer

The epidemiology of head and neck cancer can be accounted for largely in terms of known carcinogens introduced into the body through the mouth. Though there are many environmental exposures--such as asbestos, radon, nickel and arsenic--which have strong carcinogenic effects, most of these have only a small impact on the general population because exposure is limited, usually to small occupational groups. Two prevalent exposures, however, tobacco and alcohol, are strong risk factors for nearly all sites in the head and neck, and together account for about 80%-90% of all cancers of the head and neck. There is evidence for biologic interaction between some occupational exposures and cigarette smoking for cancer of the lung, and tobacco and alcohol for cancer of the mouth. Based on this evidence for biologic interaction and the prevalence of smoking, it seems likely that tobacco is related to about 80% of all cancers of the head and neck in the United States.     

Cytogenetics in head and neck cancer

Cytogenetics or the study of chromosomes has been an important tool in oncology. It localizes the abnormality on a particular chromosome segment as such but, the molecular analysis on the other hand focuses the exact gene of interest. Hence both are complimentary. Classical cytogenetics in combination with recent molecular techniques has given rise to various molecular cytogenetic analytical techniques such as florescent in-situ hybridization (FISH), spectral karyotyping (SKY) and comparative genomic hybridization (CGH). The role of telomeres and its concerned enzyme telomerase is important in carcinogenesis. This article summarizes the various cytogenetic techniques and presents an overall view of the importance of cytogenetcs in head and neck cancer.     

Epidemiology of head and neck cancer

Epidemiologic considerations which are pertinent to cancer of the head and neck are broad and varied. Cigarette smoking continues to be the major cause of head and neck neoplasms. Occupational and environmental exposures to carcinogens have been well identified. Tumors may develop as a result of medical therapies. Susceptibility on a genetic basis has been shown, and the role of viruses in carcinogenesis has been further documented.     

Chemotherapy for head and neck cancer

This overview of the role of chemotherapy in head and neck cancer is based on clinical trials conducted at The Princess Margaret Hospital and on a critical review of the literature. For recurrent or metastatic squamous cell carcinoma, no drug or combination has been found superior to methotrexate, which in large series gives transient responses in about 25% of patients. Reports of higher rates of response have not correlated with increased survival, and response rates from many series have been inflated by the use of poor and variable criteria of response or by inappropriate exclusion of patients. Chemotherapy may lead to high rates of response when used initially as part of combined modality treatment with radiation and/or surgery, but longterm benefit has not yet been demonstrated. Chemotherapy should not be considered part of standard management for recurrent or metastatic head and neck cancer, and should be used as part of primary treatment for loco-regional disease only in the context of large, well designed clinical trials.