The role of human papillomaviruses (HPV) in upper respiratory tract diseases

High-risk papillomaviruses (HPVs) are etiologic agents for anogenital tract cancers and have been detected in head and neck squamous cell carcinomas. Still a viral etiology of head and neck cancers had not been established unambiguously. For head and neck cancers two major risk factors (tobacco smoke and alcohol) have been recognised and HPV infection may play a synergistic role in the multifactorial etiology of the tumors. The occurrence rates for HPV DNA in the head and neck cancers varied from one study to another because of technical and demographic variables. The HPV infection in benign head and neck diseases were also presented.     

Economic impact of human papillomavirus-associated head and neck cancers in the United States

Cases of human papillomavirus (HPV)-associated head and neck cancers are rapidly increasing in the United States. Little is known about the economic burden of these cancers. A literature review identified 7 studies that characterized aspects of the overall economic burden of HPV-associated head and neck cancers in the United States. Other cost studies are detailed to highlight the clinical reality in treating these patients. As the clinical awareness of the role of HPV in head and neck cancers continues, the economic impact of cancers caused by this virus will have implications for the role of various preventive measures.     

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   

口咽部鳞状细胞癌与性行为和人乳头状瘤病毒感染

高危型人乳头状瘤病毒感染(high risk human papillomavirus, HR HPV)是头颈部鳞状细胞癌发生的一个重要相关因素,特别是原发口咽部、缺少烟酒等危险因素的患者。口咽肿瘤中确认发现HR HPV,以及流行病学病例对照研究明确HR HPV与口咽癌发病风险的关系,已阐明了二者的联系。重点论述口咽癌患者与非口咽癌患者在口腔、喉腔和下咽部位的比较及性行为方式的影响。明确头颈肿瘤的性行为危险因素对未来肿瘤预防是必不可少的,同时以利于理解现有的HPV疫苗对未来头颈肿瘤预防的潜在作用。同时还扩展到性行为作为口咽癌发生的一个危险因素以及其作为HPV暴露标记的作用,强调HR HPV是通过性行为传播到上呼吸消化道,增加HPV相关的口咽癌的发病风险。     

New aspects of HPV-positive head and neck cancer. Highlights from the 2011 ASCO Congress

HPV-positive head and neck carcinoma is significantly different than tobacco- and alcohol-induced cancer. Between 30% and 50% of oropharyngeal cancers are associated with human papillomavirus (HPV). Studies still show an increasing incidence. HPV-positive head and neck cancer patients have a better prognosis due to a better response to therapy. Especially patients with gene overexpression of immunological proteins in the antigen presentation are suggested to benefit from radiotherapy. A current retrospective study shows better outcomes for patients treated with radiotherapy in combination with biological targets compared to radiochemotherapy.     

Detection of human papillomavirus in clinical samples

The confirmation of human papillomavirus (HPV) as a causative agent for a subset of squamous cell carcinomas of the head and neck has resulted in a growing expectation for HPV testing in head and neck cancers. An increasing understanding of HPV-related tumorigenesis has informed this evaluation process in a manner that is moving wide scale, indiscriminant, and nonstandardized testing toward a more directed, clinically relevant, and standardized approach. This review addresses the current state of HPV detection and focuses on the importance, appropriate time, and need for HPV testing.     

Role of human papillomavirus in the development of head and neck squamous cell carcinomas

OBJECTIVE: To review the literature on the role of oncogenic human papillomaviruses (HPVs) in the carcinogenesis of the head and neck mucosa. MATERIAL AND METHODS: Molecular and epidemiological studies concerning the high-risk HPV types and their role in carcinogenesis in the head and neck region were screened. RESULTS: Different studies revealed that: (i) 15-25% of head and neck squamous cell carcinomas (HNSCCs) are clonally associated with high risk HPV types (type 16); (ii) the oropharynx and particularly the tonsils are the most susceptible sites; (iii) patients with HPV-positive tumours present with more advanced stages of disease, are relatively younger, do not have extravagant tobacco and alcohol intake and seem to have a better survival; (iv) HPV-positive tumours are characterized by poor differentiation grade and a basaloid appearance; and (v) HPV-positive tumours exhibit integrated HPV DNA, wild-type p53, pRb downregulation and overexpression of p16INK4A. CONCLUSION: Taken together, these data support the view that HPV-harbouring HNSCC can be considered a discrete tumour entity with, moreover, a favourable prognosis. Screening of patients, especially those with tonsillar cancers, for the presence of HPV may help to further optimize treatment protocols and to provide more accurate prognostic information.     

Neue Aspekte HPV-positiver Kopf-Hals-Karzinome

HPV-positive head and neck carcinoma is significantly different than tobacco- and alcohol-induced cancer. Between 30% and 50% of oropharyngeal cancers are associated with human papillomavirus (HPV). Studies still show an increasing incidence. HPV-positive head and neck cancer patients have a better prognosis due to a better response to therapy. Especially patients with gene overexpression of immunological proteins in the antigen presentation are suggested to benefit from radiotherapy. A current retrospective study shows better outcomes for patients treated with radiotherapy in combination with biological targets compared to radiochemotherapy.     

Hereditary and environmental factors associated with risk and progression of head and neck cancer.

The familial occurrence of head and neck cancers supports the role of heredity in this disease group. The roles of environmental and genetic factors are difficult to separate. There are several well-characterized entities, however, that are associated with risk and prognosis of head and neck cancer, including Lynch-II syndrome, Bloom syndrome, Fanconi's anemia, xeroderma pigmentosum, ataxia telangiectasia, and Li-Fraumeni syndrome. Mutagen-induced chromosomal damage is associated with an increased risk of multiple primary neoplasms and upper aerodigestive tract cancers. A possible reduction of genotoxicity, mediated by micronutrients, was demonstrated in vitro. Sister chromatid exchanges and micronuclei are useful exposure and disease markers. Metabolic changes (acetylation, DBQ phenotype, and the AH locus polymorphism) have been found to be associated with cancer of the upper aerodigestive tract. Most associations between histocompatibility antigens and solid tumors are relatively weak, probably because of the masking effects of environmental factors. Infections by HPV, EBV, and HSV have a causative or predisposing role in several types of head and neck cancer. Amplification and rearrangement of oncogenes may also play a role in carcinogenesis, and oncogene amplification may be associated with aggressive tumor behavior and unfavorable clinical prognosis. Ploidy of tumors seems to be an important determinant of survival and response to therapy.     

Evaluation and application of a broad-spectrum polymerase chain reaction assay for human papillomaviruses in the screening of squamous cell tumours of the head and neck

OBJECTIVE: The results of studies analysing the prevalence of human papillomaviruses (HPVs) in squamous cell carcinomas of the head and neck region often vary depending on the different molecular biological methods applied. Focusing on the histomorphological criteria of HPV infections, the percentage of HPV-positive cancers should be higher than has been found in most studies. The aim of this study was to increase the detection spectrum of HPV polymerase chain reaction (PCR) screening using degenerate consensus primers. MATERIAL AND METHODS: To increase the sensitivity of the assay to one copy of HPV DNA per cell, a two-step PCR was carried out. The products were directly sequenced by means of a cycle sequencing approach. Seventy biopsies from squamous cell carcinomas of the upper aerodigestive tract were screened using the primer system. RESULTS: According to the PCR results, 0/2 carcinomas of the floor of the mouth or tongue, 7/16 biopsies of oropharyngeal cancers, 3/13 hypopharyngeal cancers, 13/34 squamous cell carcinomas of the larynx, 4/4 biopsies from carcinomas of the nasal cavity or paranasal sinuses and 1/1 squamous cell carcinoma of the parotid gland were positive. CONCLUSION: This broad-spectrum PCR can effectively detect HPV in head and neck cancers.     

Evaluation and application of a broad-spectrum polymerase chain reaction assay for human papillomaviruses in the screening of squamous cell tumours of the head and neck

Objective—The results of studies analysing the prevalence of human papillomaviruses (HPVs) in squamous cell carcinomas of the head and neck region often vary depending on the different molecular biological methods applied. Focusing on the histomorphological criteria of HPV infections, the percentage of HPV-positive cancers should be higher than has been found in most studies. The aim of this study was to increase the detection spectrum of HPV polymerase chain reaction (PCR) screening using degenerate consensus primers. Material and Methods—To increase the sensitivity of the assay to one copy of HPV DNA per cell, a two-step PCR was carried out. The products were directly sequenced by means of a cycle sequencing approach. Seventy biopsies from squamous cell carcinomas of the upper aerodigestive tract were screened using the primer system. Results—According to the PCR results, 0/2 carcinomas of the floor of the mouth or tongue, 7/16 biopsies of oropharyngeal cancers, 3/13 hypopharyngeal cancers, 13/34 squamous cell carcinomas of the larynx, 4/4 biopsies from carcinomas of the nasal cavity or paranasal sinuses and 1/1 squamous cell carcinoma of the parotid gland were positive. Conclusions—This broad-spectrum PCR can effectively detect HPV in head and neck cancers.     

Role of human papillomavirus in the development of head and neck squamous cell carcinomas

Objective To review the literature on the role of oncogenic human papillomaviruses (HPVs) in the carcinogenesis of the head and neck mucosa.

Material and Methods Molecular and epidemiological studies concerning the high-risk HPV types and their role in carcinogenesis in the head and neck region were screened.

Results Different studies revealed that: (i) 15–25% of head and neck squamous cell carcinomas (HNSCCs) are clonally associated with high risk HPV types (type 16); (ii) the oropharynx and particularly the tonsils are the most susceptible sites; (iii) patients with HPV-positive tumours present with more advanced stages of disease, are relatively younger, do not have extravagant tobacco and alcohol intake and seem to have a better survival; (iv) HPV-positive tumours are characterized by poor differentiation grade and a basaloid appearance; and (v) HPV-positive tumours exhibit integrated HPV DNA, wild-type p53, pRb downregulation and overexpression of p16^INK4A.

Conclusion Taken together, these data support the view that HPV-harbouring HNSCC can be considered a discrete tumour entity with, moreover, a favourable prognosis. Screening of patients, especially those with tonsillar cancers, for the presence of HPV may help to further optimize treatment protocols and to provide more accurate prognostic information.     

Epidemiology of human papillomavirus-related head and neck cancer

Human papillomavirus (HPV) is now recognized to cause a subset of head and neck squamous cell carcinomas (HNSCC). Although excessive tobacco and alcohol use continue to be important risk factors for HNSCC, epidemiologic studies suggest that more than 25% of HNSCC are now caused by HPV. The incidence of HPV-related HNSCC is increasing, highlighting the need to understand the oral HPV infections causing these cancers. This article reviews the evidence for a causal association between HPV and HNSCC, examines the changing epidemiologic trends of HNSCC, and discusses what is currently known about oral HPV infection, natural history, and transmission.     

Human papillomavirus and oropharyngeal squamous cell carcinoma: what the clinician should know

The incidence of oropharyngeal squamous cell carcinoma (OPSCC) is rising in contrast to the decreasing incidence of carcinomas arising in other subsites of the head and neck. The human papillomavirus (HPV) infection has played an increasing role in these epidemiological changes and as the etiology for a significant fraction of head and neck squamous cell carcinomas, OPSCC in particular. Most importantly, many retrospective studies have shown that the prognosis differs significantly between patients with HPV-associated tumors and non-HPV associated tumors. Thus, questions arise on the choices of treatment for patients based on HPV status and the consequences of therapy. Given the recognized relevance of HPV status in OPSCC, many new questions concerning the biology, treatment, and prevention of HPV infection arise. This review is intended to highlight some of the major issues and frequently asked questions relevant for the clinician dealing with patients with OPSCC.     

Human Papillomavirus (HPV) – Structure,epidemiology and pathogenesis

The number of cancers is constantly increasing. An important role in the etiology of many of them is played by the viral factor, by oncogenic viruses, such as the Human Papillomavirus. The article shows current epidemiological situation and describes the structure of the virus and modes of transmission. It also explains the role of HPV infection in cancer with particular emphasis on oropharynx and head and neck cancer.     

Predictive factors for diagnosis of advanced-stage squamous cell carcinoma of the head and neck

OBJECTIVE: To identify the predictive factors (with emphasis on diagnostic delay) associated with the diagnosis of an advanced-clinical stage head and neck cancer. DESIGN: Cross-sectional study of patients with head and neck cancer originally recruited for a case-control study. SETTING: Three referral oncological centers in metropolitan areas in southern Brazil: S?o Paulo, Curitiba, and Goiania. PATIENTS: The study population comprised 679 patients recently diagnosed as having a previously untreated head and neck squamous cell carcinoma. MAIN OUTCOME MEASURE: Diagnosis of advanced disease (clinical stage III-IV) head and neck cancer. RESULTS: Patients with laryngeal and hypopharyngeal cancers were more likely to be diagnosed as having advanced disease than those with lip, oral, and oropharyngeal cancers (88.0% vs 74.6%) (P<.001). Patient delay was inversely associated with clinical stage at diagnosis in patients with the same cancers, while professional delay was directly associated with a higher risk of advanced clinical stage at diagnosis (P =.001 and P =.006, respectively). In the analysis of laryngeal and hypopharyngeal cancer, both patient and professional delays were associated with advanced disease, with patient delay being a stronger predictive factor than professional delay. CONCLUSIONS: Clinical stage at diagnosis was associated with sociodemographic characteristics, patient delay, and professional delay. Our results indicate that continued educational programs for the population and health care professionals regarding the identification of early symptoms of head and neck cancers are warranted.     

Human papillomavirus, smoking, and head and neck cancer

Aims

Smoking and human papillomavirus (HPV) are both distinct risk factors for head and neck cancer, but the nature of interaction between these 2 risk factors in the development of head and neck cancer remains unclear. The purpose of this review is to determine the potential effect of smoking in causation of HPV-related head and neck carcinoma.

Method

A literature search was carried out using the keywords human papillomavirus, head and neck cancer, smoking, tobacco, and cervical cancer. The English-language articles, references, and other relevant studies evaluating the association of smoking, HPV, and risk of head and neck cancer were collected and analyzed.

Conclusion

Overall, our review points to smoking tobacco posing an additional risk for development of head and neck cancer in the presence of HPV infection. This is consistent with available laboratory data that show evidence of biological plausibility for interaction between smoking and progression of HPV infection to carcinogenesis. It is therefore important that cessation of smoking is promoted in smokers with HPV infection.     

71例头颈部鳞状细胞癌的多原发癌临床资料分析

目的　了解头颈部鳞癌的多原发癌发病部位和治疗、生存状况。方法　对 71例头颈部鳞状细胞癌 (简称鳞癌 )的多原发癌临床资料做了回顾性分析。结果　发生在头颈部的重复癌 2 7例 ,发生在非头颈部的重复癌 4 2例 ,另有三重癌 2例。本组共有同时性重复癌 4例 ,其中 1例是同时性三重癌。余 6 7例均为异时性重复癌 ,其中 1例为异时性三重癌。 6 7例异时性重复癌中 ,先证癌与重复癌发生的间隔期为 8个月～ 12年不等。 70 %的先证口腔鳞癌发生头颈部重复癌 ;6 2 %的先证下咽癌和 79%的先证喉癌发生非头颈部位的重复癌。非头颈部位以食管和肺部发生的重复癌较多。在所有头颈部鳞癌发生重复癌的部位中 ,以食管重复癌为最多 ,占本组病例的 2 4 %。本组病例总体3年、5年生存率分别为 32 4 %和 2 2 5 % ;重复癌治疗组和未治组的 3年生存率有明显统计学差异 ,治疗组明显高于未治组。结论　头颈鳞癌的重复癌以食管癌最为多见。口腔癌容易发生头颈部重复癌 ,喉癌和下咽癌易发生非头颈部重复癌。细致随访和复查、早期明确诊断和积极有效的治疗 ,可以提高这类患者的生存率。     

Tumormarker und Biomarker bei Hals-Kopf-Tumoren

The early detection of recurrences after surgical or radiation treatment of squamous cancers of the head and neck is often difficult. A rise in circulating tumor marker levels such as SCCA and CEA often precedes the clinical appearance of recurrences by about several months. The combined analysis of SCCA and CEA can facilitate the early detection of local relapse or distant recurrence and can therefore accelerate specific diagnostic and/or therapeutic procedures. Therefore, after primary therapy of locally advanced head and neck cancers, the combined analysis of SCCA and CEA normally every 3-6 months can be recommended. Molecular markers give increasing insight into tumor biology, prognosis and response to chemotherapy, radiation and molecular targeted therapies. Biomarkers require a careful validation before being implemented into clinical decision making, but promising markers such as EGFR, p53 and HPV oncogene may become important stratification factors for individualized tumor treatment algorithms.