Demographic and risk factors in patients with head and neck tumors

The association between human papillomavirus (HPV) infection and the development of head and neck cancer has been documented recently. In this study on 86 head and neck cancer patients and 124 controls, data regarding demographics, behavioral risk factors, and risks related to HPV exposure were collected. HPV detection was carried out using polymerase chain reaction in the tumors and in oral exfoliated cells, and HPV typing by a reverse line blot assay specific for 37 HPV types. Sera were tested by an enzyme‐linked immunosorbent assay specific for HPV proteins. Head and neck cancer cases report significantly more oral‐anal contact (P = 0.02) and tobacco and alcohol use than controls (P = 0.001; P = 0.02, respectively). High‐risk HPV DNA was detected in 43% of oral washings of cases and 4% of controls (P < 0.0001). The association between the presence of high‐risk HPV DNA in oral exfoliated cells and in tumor tissues was statistically significant (adjusted P < 0.0001). The prevalence of HPV‐specific antibodies was significantly higher in cases than in controls (adjusted P < 0.0001). These results provide epidemiological and immunological evidence for HR HPV as a strong risk factor (OR = 44.3, P < 0.0001) for head and neck cancer, even after controlling for age, tobacco and alcohol use. The detection of high‐risk HPV DNA in oral exfoliated cells and HPV‐specific antibodies in serum can be considered as clinically relevant surrogate markers for the presence of a HPV‐associated head and neck cancer, with a high sensitivity (83%) and specificity (88%). J. Med. Virol. 81:878–887, 2009. © 2009 Wiley‐Liss, Inc.     

Analysis of human papillomavirus prevalence and TP53 polymorphism in head and neck squamous cell carcinomas

Head and neck squamous cell carcinoma is a disease associated with tobacco and alcohol abuse. There is evidence that the oncogenic human papillomavirus (HPV) may also be a risk for upper aerodigestive tract cancers. High-risk HPVs encode two early proteins, E6 and E7, that can bind to p53 and pRb, respectively, and induce its degradation or inactivation. The TP53 gene has a single polymorphism at codon 72 of exon 4 that encodes either arginine (Arg) or proline (Pro). The purpose of this study was to evaluate the role of HPV infection and TP53 polymorphism in head and neck cancer. We analyzed 50 tumors, as well swabs of oral mucosa from 142 control individuals, with a polymerase chain reaction technique. The prevalence of HPV in controls was 10.6% and in cancer specimens 16%. The frequency distribution of genotypes in controls was 50% Arg/Arg, 43% Arg/Pro and 7% Pro/Pro; in tumors, it was 52% Arg/Arg, 32% Arg/Pro, and 16% Pro/Pro. Contrary to the results of some studies on cervical cancer, no association between any TP53 genotype or allele and the development of head and neck cancer was observed, regardless of HPV status, except for the Pro/Pro genotype, which is associated with the absence of HPV. The arginine allele appears to protect against head and neck cancers. Also, the data showed that HPV infection results in no increased risk of developing head and neck tumors.     

Investigation of the occurrence of torque tenovirus in malignant and potentially malignant disorders associated with human papillomavirus

In a previous pilot study, a significantly poorer outcome of laryngeal cancer was found in patients co‐infected with human papillomavirus (HPV) and genogroup 1 torque tenovirus (TTV). The present study aimed to collect data on the overall prevalence of TTVs on the prevalence of genogroup 1 TTV in two other malignancies associated with HPV, oral squamous cell cancer and cervical cancer, and in oral and cervical premalignant lesions (oral lichen planus, oral leukoplakia, cervical atypia). Oral samples from all patients were accompanied with a sample from the healthy mucosa. The overall prevalence of TTV was significantly higher both in oral squamous cell cancer and cervical cancer compared with other patient groups or with the respective controls. The prevalence of genogroup 1 TTV was significantly higher in lesions of oral squamous cell cancer and oral lichen planus, but not in lesions of oral leukoplakia (24.6%, 10.1%, and 4.5%, respectively), compared with the prevalence in the oral cavity of controls (1.4%). Co‐infection rates with genogroup 1 TTV and HPV were significantly higher in oral squamous cell cancer than in controls, oral lichen planus or oral leukoplakia patients (12.3%, 0.0%, 6.7%, and 4.5%, respectively). The prevalence of genogroup 1 TTV in all cervical samples were comparable. These data suggest that genogroup 1 TTV may be associated specifically with some head and neck mucosal disorders, but disproves a (co)carcinogenic role in oral cancer or cervical cancer as well as an association with HPV or with malignancies associated with HPV. J. Med. Virol. 81:1975–1981, 2009. © 2009 Wiley‐Liss, Inc.     

TP53 gene expression in HPV-positive oral tongue SCC and its correlation with nodal metastasis

In this study, we investigated the prevalence of human papilloma virus (HPV) infection and TP53 expression in patients with squamous cell carcinoma (SCC) of the tongue and, subsequently, its significance in cervical lymph node metastases and tumor differentiation. Sections of formalin-fixed, paraffin-embedded tissue blocks from 94 histologically confirmed tongue SCC cases were investigated in this study. Immunohistochemistry was used to study TP53 expression, and polymerase chain reaction (PCR) was performed for the detection of high risk HPV types (16 and 18). The frequency of HPV-16 and HPV-18 infection was 10.6% and 16%, respectively. Overexpression of TP53 was observed in 70.2% of patients. Young patients (aged below 45 years) comprised 20% of all patients. There was no significant association between TP53, HPV-16, or HPV 18 presence and higher stages of the tumor, tumor differentiation, or presence of nodal metastasis. Although an association between head and neck SCC and HPV infection is being recognized and reported, our data implicate that HPV infection or TP53 expression does not play a significant role in oral tongue SCC pathogenesis, differentiation, or metastasis, as seen in our patients.     

Human papillomavirus infections and oral tumors

In the past 20 years, there has been an increasing interest in human papillomaviruses (HPV) because of their potential role in the pathogenesis of malignant tumors. In 1983, we published the first evidence that HPV might be involved in oral squamous cell carcinomas. The identification of morphological similarities between oral and cervical mucosa lead us to this original proposal. In a recent meta-analysis, HPV was indeed confirmed as an independent risk factor for oral carcinoma. To date, totally more than 100 types of HPV have been identified. As in anogenital cancers, HPV type 16 is the most prevalent type in oral carcinomas. The benign oral lesions, associated with HPV infection, include squamous cell papilloma, condyloma acuminatum, verrucca vulgaris and focal epithelial hyperplasia (FEH). Papillomas and condylomas are mostly caused by HPV type 6 or 11, while oral verrucas are associated with the skin types 2 or 4. A family history of FEH has been suggested. The FEH lesions are caused by HPV types 13 and 32, only detected in oral epithelium. In immunocompromised patients, benign HPV-induced lesions are characterized by atypical morphology and the simultaneous detection of multiple HPV types. Oral benign HPV lesions are mostly asymptomatic, and may persist or regress spontaneously.     

Human papillomavirus infection: Epidemiology,biology, host interactions,cancer development,prevention, and therapeutics

Human papillomavirus (HPV) infection is one of the most common sexually transmitted infections worldwide. It is caused by the HPV, a DNA virus that infects epithelial cells in various mucous membranes and skin surfaces. HPV can be categorised into high-risk and low-risk types based on their association with the development of certain cancers. High-risk HPV types, such as HPV-16 and HPV-18, are known to be oncogenic and are strongly associated with the development of cervical, anal, vaginal, vulvar, penile, and oropharyngeal cancers. These types of HPV can persist in the body for an extended period and, in some cases, lead to the formation of precancerous lesions that may progress to cancer if left untreated. Low-risk HPV types, such as HPV-6 and HPV-11, are not typically associated with cancer but can cause benign conditions like genital warts. Genital warts are characterised by the growth of small, cauliflower-like bumps on the genital and anal areas. Although not life-threatening, they can cause discomfort and psychological distress. HPV is primarily transmitted through sexual contact, including vaginal, anal, and oral sex. It can also be transmitted through non-penetrative sexual activities that involve skin-to-skin contact. In addition to sexual transmission, vertical transmission from mother to child during childbirth is possible but relatively rare. Prevention of HPV infection includes vaccination and safe sexual practices. HPV vaccines, such as Gardasil and Cervarix, are highly effective in preventing infection with the most common high-risk HPV types. These vaccines are typically administered to adolescents and young adults before they become sexually active. Safe sexual practices, such as consistent and correct condom use and limiting the number of sexual partners, can also reduce the risk of HPV transmission. Diagnosis of HPV infection can be challenging because the infection is often asymptomatic, especially in men. In women, HPV testing can be done through cervical screening programs, which involve the collection of cervical cells for analysis. Abnormal results may lead to further diagnostic procedures, such as colposcopy or biopsy, to detect precancerous or cancerous changes. Overall, HPV infection is a prevalent sexually transmitted infection with significant implications for public health. Vaccination, regular screening, and early treatment of precancerous lesions are key strategies to reduce the burden of HPV-related diseases and their associated complications. Education and awareness about HPV and its prevention are crucial in promoting optimal sexual health. This study aimed to carry out a literature review considering several aspects involving HPV infection: Global distribution, prevalence, biology, host interactions, cancer development, prevention, therapeutics, coinfection with other viruses, coinfection with bacteria, association with head and neck squamous cell carcinomas, and association with anal cancer.     

Human papilloma virus associated head and neck cancer: A PCR based study

Head and neck cancers (HNC), 90% of which are squamous cell carcinomas (SCC), rank sixth among all malignancies worldwide and comprise 40-50% of the total number of malignancies in India. In addition to alcohol and tobacco usage, which is the major source of oral carcinogens, viruses such as human papilloma virus (HPV) may also contribute to development of the malignancy. The aim of this study was to identify the prevalence of HPV in head and neck cancers using material from metastatic site. A total of 111 cases of neck nodal metastases were included in this study. The primary was identified as oral cavity, oropharynx and nasopharynx. In a subset, the primary remained "unknown." Polymerase chain reaction was carried out to detect HPV DNA on the fine needle aspirates. HPV was detected in 32.4% cases. Maximum positivity was observed in metastases from primary in the oral cavity (47.1%) with tongue (55%), followed by oropharynx (25%) and nasopharynx (5%) cases. In the unknown primary group, HPV was detected in 52.9% cases. Study defines the association of HPV with HNC in population of northern India. There was varied association of HPV depending on site of primary tumor arising in mucosal surfaces of head and neck region.     

The Role of Human Papilloma Virus (HPV) Infection in Non-Anogenital Cancer and the Promise of Immunotherapy: A Review

Over the past 30 years, human papilloma virus (HPV) has been shown to play a role in the development of various cancers. Most notably, HPV has been linked to malignant progression in neoplasms of the anogenital region. However, high-risk HPV has also been suggested to play a significant role in the development of cancers in other anatomic locations, such as the head and neck, lung, breast and bladder. In 2006, the first vaccine for HPV, Gardasil, was approved for the prevention of subtypes 6, 11, 16 and 18. A few years later, Cevarix was approved for the prevention of subtypes 16 and 18, the HPV subtypes most frequently implicated in malignant progression. Although increased awareness and vaccination could drastically decrease the incidence of HPV-positive cancers, these approaches do not benefit patients who have already contracted HPV and developed cancer as a result. For this reason, researchers need to continue developing treatment modalities, such as targeted immunotherapies, for HPV-positive lesions. Here, we review the potential evidence linking HPV infection with the development of non-anogenital cancers and the potential role of immunotherapy in the prevention and eradication of HPV infection and its oncogenic sequela.     

A literature review on oral basaloid squamous cell carcinomas,with special emphasis on etiology

In the recent years, basaloid squamous cell carcinomas (BSCCs) have gained attention because of (1) observation of a relative increase in the number of tumors arising particularly in head and neck sites, (2) identification of human papillomavirus (HPV) in BSCCs arising predominantly in the oropharynx, and (3) controversies that exist regarding the biological aggressiveness of the tumor. The objective of the present review was to address the issues mentioned above by focusing primarily on oral BSCCs, using literature that has been published in the English language up to 2013. According to the literature review, oral BSCCs were found to be relatively more common in elderly patients with a mean age of 64 years. A male predominance with a male/female ratio of 3:1 was observed. The predominant site was the tongue, with almost half of the reported cases occurring at this site, followed by the floor of the mouth and palate. With reference to habit history, majority were found to be tobacco and alcohol users. However, only 3 studies revealed data on HPV status of purely oral BSCC, and according to the results of these studies, of the 17 tumors tested, 4 had harbored high-risk HPV. Furthermore, most oral BSCCs were in an advanced clinical stage, namely, stage III or IV with T3 or T4 lesions and cervical lymph node metastasis at initial presentation, whereas 41% of patients had presented with local recurrences and 45% had died of the disease. In conclusion, although, the present literature review found enough evidence to consider tobacco and alcohol as risk factors for the development of oral BSCC, steps should be taken to fill the gap in our knowledge that exist with reference to contribution of oncoviruses, particularly HPV in the etiology of oral BSCC.     

HPV相关的头颈部鳞状细胞癌的研究进展

随着吸烟、饮酒危险因素的相应控制,头颈部鳞状细胞癌的发病率有所下降,但是一部分由高危型HPV16/18感染引起的头颈部鳞癌的发病率却呈明显的上升趋势。HPV相关的头颈部鳞癌因特殊的致病因素而表现出独特的基因表达谱和生物学特性,且对放化疗敏感、预后良好以及有更高的生存率,因此治疗方式也有区别于其他头颈部鳞癌。本文就近些年来关于HPV相关的头颈部鳞癌流行病学特点、致癌机制以及诊断与防治作一综述。     

Typing of human papillomavirus in women with cervical lesions: Prevalence and distribution of different genotypes

Human papillomavirus (HPV) are distributed widely and persistent infection with high‐risk (HR) HPV is recognized as a necessary cause of cervical cancer. The aim of this study was to evaluate the distribution of different HR‐HPV genotypes in 199 women with cervical pre‐invasive lesions undergoing conservative treatment. A Linear Array HPV Genotyping Test was used to identify individual HPV genotypes in cervical samples. It was observed that the most prevalent HPV genotypes were HPV 16 (52.6%), HPV 51 (13.5%), and HPV 31 (10.9%); HPV 18 was found in 7.3% of the patients. Stratifying the different HPV genotypes according to the severity of the cervical lesion, a strong association between the increasing severity of the histological diagnosis and the detection of more carcinogenic HR‐HPV type was found, and in all but one cervical intraepithelial neoplasia of grade 3 the presence of at least one HR‐HPV could be detected, with more than 70% of cervical intraepithelial neoplasia of grade 3 patients bearing HPV 16. Multiple infections, comprising between 2 and 6 HPV types, were found in 43% of patients; however, the presence of more than 1 HR‐HPV type was not associated with an increased risk of high grade lesions. In conclusion, this data show that HPV 16, 51, 31, 52, and 18 were the prevalent types found in patients with cervical lesion undergoing conservative treatment, with a high prevalence of HPV 16 in cervical intraepithelial neoplasia of grade 3 patients. No association between multiple infection and severity of the lesion could be found. J. Med. Virol. 81:271–277, 2009. © 2008 Wiley‐Liss, Inc.     

The frequency of herpes simplex virus changes in anal Pap smear and its association with squamous intraepithelial lesions in high‐risk male patients

While there are studies postulating a model of synergism between human papillomavirus (HPV) and herpes simplex virus (HSV) in cervical carcinogenesis, the frequency of anal herpes as well as its association with anal squamous intraepithelial lesions (ASILs) has been understudied in men. This study evaluates the frequency of HSV changes in anal Pap smears and its association with ASILs in a high‐risk population. A computerized search for specimens associated with anal cytology that had positive findings of HSV was performed. The electronic medical records were examined for past diagnosis of herpes, HSV serology prior to or after cytology, and if the patient received treatment after cytologic diagnosis of HSV. Of the 470 anal Pap smears (Thin‐prep) examined, seven had cellular changes consistent with HSV infection. All patients were asymptomatic human immunodeficiency virus (HIV) positive males with no prior HSV serology tests. Two patients had prior diagnoses of HSV infection. Cytologic abnormalities were identified in 86% ranging from atypical squamous cells of undetermined significance to high grade squamous intraepithelial lesion. Three patients were treated after the HSV cytologic diagnosis. The frequency of HSV changes in anal Pap smear is low (1.48%), but the presence of concomitant cytologic abnormalities is high (86%). While our findings suggest the possible role of HSV as a HPV co‐factor in ASILs, larger studies are needed to support this. Identification of HSV infection on anal Pap smear is important for institution of patient treatment and subsequent reduction of transmission. Diagn. Cytopathol. 2014;42:487–490. © 2013 Wiley Periodicals, Inc.     

Molecular detection of human papillomavirus in 594 uterine cervix samples from Moroccan women (147 biopsies and 447 swabs).

Uterine cervix cancer is the second most frequent female cancer after breast cancer in Morocco and represents a public health problem. Cervical cancer is highly linked to human papillomavirus (HPV) especially types 16 and 18 which are the highly oncogenic genotypes. To identify the contribution of HPV testing in the prevention of cervical cancer in Morocco, 147 biopsies collected at the Institut National d'Oncologie and 447 swabs from pathology laboratories and gynaecologist offices in Rabat were HPV analysed. HPV testing were made without any presumption of the histopathological diagnosis. A total of 147 paraffin-embedded biopsies and 447 exfoliated cervical samples were included. Based on histopathology results of the 147 biopsies, most cervical lesions were invasive carcinomas and non specific inflammations (NSI). With the molecular assay, HPV was detected in 91/147 (62%) patients. The high risk types 16 and 18 were found in 45% of the cases (41/91) and HPV 18 in 19% of the cases (17/91). Double infection with HPV 16 and 18 was found in 3 cases. Among the 447 swabs tested, 28 were HPV positives. Cytology results showed that 46% were inflammations (13/28). Among them, 10 patients had a NSI and only 3 patients had a cytology diagnosis of HPV infection. Based on these data, HPV testing should be associated to cervical cytology screening according to two algorithms established in function of the age of the patient and viral natural history. Combination of cytology and HPV testing allow identification of patient with high risk for development of high grade cervical lesions and improve cervical cancer prevention.     

Adjuvant targeted therapy with trastuzumab may decrease metastatic capacity in specific group of oropharyngeal cancer patients: downregulation of E-cadherin-catenin complex by cooperative effect of erbB-2 and human papillomavirus type 16 E6/E7 protooncogenes

Human papillomavirus (HPV) type 16 is causally associated with a subset of oral cancers, predominantly those cancers arising in the oropharynx (OP). Increased HPV16 E6 and E7 oncogene expressions are responsible for the malignant transmission in these cancers. ErbB-2 is the family member most closely implicated in human cancer, where it is overexpressed in about 30% of carcinomas including head and neck squamous cell carcinoma. Coexpressions of E6/E7 and ErbB-2 downregulate E-cadherin and catenin expression, therefore induces metastatic process. Trastuzumab is a humanized monoclonal antibody that recognizes the ErbB-2 protein receptor and breakthrough in the treatment of metastatic breast cancer in combination with chemotherapeutic agents. This antibody is also in clinical testing for adjuvant treatment of breast cancer. We propose that trastuzumab as an adjuvant treatment may decrease process of tumor metastasis in oropharyngeal cancer patients who completed primary treatment (surgery and/or radiotherapy) and show expression of both HPV16 E6/E7 and erbB-2 oncoproteins. In vitro and in vivo studies with trastuzumab in these subgroup of patients may support our hypothesis.     

Human papillomavirus-positive tonsillar carcinomas: a different tumor entity?

Human papillomavirus (HPV) infections are thought to be one of the causal factors in the development of head and neck squamous cell carcinomas (HNSCC), particularly in tumors arising from the Waldeyer's tonsillar ring. We screened 98 carefully stratified HNSCC and different control tissues for the presence of HPV DNA by nested polymerase chain reaction (PCR) specific for genital- and Epidermodysplasia verruciformis (EV)-associated HPVs and by HPV16-specific single step PCR. Typing was performed by direct sequencing and/or sequencing of cloned amplimers. On average HNSCC showed rather low HPV DNA prevalences; 18% of the oral cavity cancers, 8% of nasopharyngeal cancers, 25% of hypopharyngeal cancers and 7% of laryngeal cancers were HPV DNA positive. In contrast, HPV sequences could be detected in 45% of the oropharyngeal cancers, particularly tonsillar carcinomas (58%). Tonsillar carcinomas were significantly more likely to be HPV positive than tumors from any other site ( P<0.001). All tonsillar cancers contained oncogenic HPV types, predominantly HPV16 (13 of 14; 93%). Unaffected tonsils were available from two of these patients, but both tested negative for HPV DNA. Furthermore, no HPV DNA could be found in tonsillar biopsy specimens from control groups. Localization and load of HPV DNA was determined in HPV16-positive tonsillar carcinomas, their metastases and in unaffected mucosa using laser-assisted microdissection and subsequent real time fluorescence PCR. We demonstrated that the HPV genome is located in the cancer cells, whereas the infection of normal mucosa is a rare event. Quantification of HPV16 DNA in samples of seven patients yielded viral loads from 6 to 153 HPV DNA copies per beta-globin gene copy and the load values in both locations were roughly comparable. These loads are comparable with data shown for other HPV-associated lesions. Statistical evaluation of data related to clinicopathological parameters showed a significant correlation of the HPV positivity of tonsillar carcinomas with tumor grading ( P=0.008) and alcohol consumption ( P=0.029). Taken together our findings show a preferential association of HPV DNA with tonsillar carcinomas. Furthermore our results argue for HPV-positive tonsillar carcinomas representing a separate tumor entity, which is less dependent on conventional HNSCC risk factors.     

Lack of evidence for an association between seminoma and human papillomavirus infection using GP5+/GP6+ consensus primers

Testicular germ cell tumors account for about 1% of all cancers. The incidence of these tumors is increasing and they represent the most common solid malignancies of young men aged 15–40 years with seminoma being one of the most common histotype. Pathogenesis of testicular germ cell tumors remains unknown and, although cryptorchidism is considered the main risk factor, there is evidence of an association with environmental and genetic risk factors. Human papillomaviruses (HPV) are a family of DNA viruses and represent a major risk factor for cervical cancer. In addition, they have been associated with other human non‐malignant and malignant diseases, including breast and head and neck cancer. HPV sequences have been detected throughout the male lower genitourinary tract as well as in seminal fluid and an increased testicular tumorigenesis has been reported in HPV transgenic mice. Aim of this study was to evaluate the potential involvement of HPV in human testicular tumorigenesis. Real‐time PCR employing GP5+/GP6+ consensus HPV primers was used to examine the presence of HPV sequences in a subset of human seminoma (n = 61) and normal testicles (n = 23). None of the specimens tested displayed the presence of HPV DNA. These findings do not support an association between HPV and human seminoma and warrant further studies to assess definitively the role of these viruses in human testicular tumorigenesis. J. Med. Virol. 85:105–109, 2012. © 2012 Wiley Periodicals, Inc.     

Impact of HPV infection on the development of head and neck cancer

Human papillomavirus (HPV)-related head and neck squamous cell carcinoma (HNSCC) is considered to be a distinct clinical entity with better prognosis than the classical tobacco- and alcohol-associated tumors. The increasing incidence of this neoplasia during the last decades highlights the need to better understand the role of HPV in the development of these cancers. Although the proportion of HNSCC attributed to HPV varies considerably according to anatomical site, overall approximately 25% of all HNSCC are HPV-DNA positive, and HPV-16 is by far the most prevalent type. In this review we discuss the existing evidence for a causal association between HPV infection and HNSCC at diverse anatomical head and neck subsites.     

头颈部小圆细胞恶性肿瘤临床特点分析

目的 探讨头颈部小圆细胞恶性肿瘤的临床、影像学、病理特点,为临床早期诊断提供理论依据。方法 回顾青岛大学附属医院耳鼻咽喉科2008年6月~2018年5月诊治的组织病理学特点为小圆细胞的恶性肿瘤290例患者的病历资料,总结其临床特点、影像学及病理特点。结果 ①头颈部小圆细胞恶性肿瘤主要好发于鼻腔、鼻窦、鼻咽及颅底区,耳及喉部极少见,可向颅内、眼眶等临近部位浸润,也可转移至颈部淋巴结或远处转移。临床症状以鼻塞、鼻出血、嗅觉减退等为主;②小细胞神经内分泌癌和非角化性癌以男性多见,恶性黑色素瘤和小细胞神经内分泌癌见于40岁以上的中老年人群。横纹肌肉瘤各年龄段均可发生;③所有肿瘤影像学上均可见软组织占位及骨质破坏,病理组织形态学均表现为分化差的小圆细胞肿瘤。结论 头颈部小圆细胞恶性肿瘤发病率低,其发病部位及症状无明显特异性,病理学形态、影像学及临床特征多无明显特异性,难以鉴别,容易误诊。目前免疫组织化学检测仍是小圆细胞恶性肿瘤确诊的主要方法,而此类疾病恶性程度较高、侵袭性强,往往确诊时病变范围已较大,影响治疗及预后,早期诊断早期治疗可以提高患者生存率。     

Abnormal cell-cycle expression of the proteins p27, mdm2 and cathepsin B in oral squamous-cell carcinoma infected with human papillomavirus

Since the role of human papillomavirus (HPV) infection in oral carcinogenesis is still unclear, the purpose of this study was to verify the association between the expression of p27, mdm2 and cathepsin B and by HPV-related oral lesions. Fifty-five oral biopsies were studied and HPV detection and typing (6/11, 16, 18, 31 and 33) were performed using polymerase chain reaction techniques. The distribution p27, mdm2 and cathepsin B was determined by immunohistochemistry. Twenty-one (38%) out of the 55 oral lesions tested positive for HPV, of which 6 (33%) were HPV 6/11, 1 (5%) was HPV 16, 14 (72%) were HPV 18 and none was HPV 33/31. Among the 55 biopsies, immunopostivity for p27, mdm2 and cathepsin B was observed in 17 (30.9%), 37 (67.2%) and 37 (67.2%), respectively. Among 21 HPV-positive oral lesions, immunopostivity of mdm2, p27 and cathepsin B was found, respectively, in 6 (33%) out of 18 benign lesions (BL), 4 (22%) out of 18 potential malignant epithelial lesions (PMEL) and 11 (57.9%) out of 19 malignant lesions (ML). High-risk HPV types may be associated with oral carcinoma, by cell-cycle control dysregulation, contributing to oral carcinogenesis and the overexpression of mdm2, p27 and cathepsin B.     

Development and clinical evaluation of a highly sensitive DNA microarray for detection and genotyping of human papillomaviruses

Human papillomavirus (HPV) has been found in cervical cancer, tonsillar cancer, and certain types of head and neck cancers. We report on a DNA microarray-based method for the simultaneous detection and typing of HPVs. The genotype spectrum discriminated by this HPV DNA microarray includes 15 high-risk HPV genotypes and 12 low-risk HPV genotypes. The HPV DNA microarray showed high degrees of specificity and reproducibility. We evaluated the performance of the HPV DNA microarray by application to three HPV-positive cell lines (HeLa, Caski, and SiHa cells) and two HPV-negative cell lines (C33A and A549 cells). The HPV DNA microarray successfully identified the known types of HPV present in the cell lines. The detection limit of the HPV DNA microarray was at least 100-fold higher than that of PCR. To assess the clinical applicability of the HPV DNA microarray, we performed the HPV genotyping assay with 73 nonmalignant and malignant samples from 39 tonsillar cancer patients. Twenty-five of the 39 (64.1%) malignant samples were positive for HPV, whereas 3 of 34 (8.8%) nonmalignant samples were positive for HPV. This result shows a preferential association of HPV with tonsillar carcinomas. The correlations of the presence of HPV with the grade of differentiation and risk factors were not significant. Our data show that the HPV DNA microarray may be useful for the diagnosis and typing of HPV in large-scale epidemiological studies.