HIV感染者HPV相关口腔损害研究现状

艾滋病病毒（HIV）的感染尤其是高效抗逆转录病毒治疗,使口腔人类乳头状瘤病毒（HPV）感染的感染率增加。本文旨在对HIV感染相关的HPV口腔流行病学特征和基因型分布等方面的国内外的研究进展进行综述。     

艾滋病感染者口腔疣状肿块人类乳头状瘤病毒感染与P53,Ki-67蛋白过度表达

目的 :了解艾滋病感染者口腔黏膜疣状肿块细胞生物学特性。方法 :应用免疫组织化学法、PCR对艾滋病感染者口腔黏膜疣状肿块、非艾滋病感染者口腔黏膜癌前病变和鳞癌组织中P5 3和Ki 67蛋白、人类乳头状瘤病毒 (HPV ) ,巨细胞病毒 (CMV)和EB病毒 (EBV )进行检测。结果 :( 1)艾滋病感染者口腔黏膜疣状肿块中P5 3蛋白阳性表达率为 2 3 % ,Ki 67蛋白阳性表达率为 76% ,二者均低于非艾滋病感染者口腔黏膜鳞癌(P <0 .0 5 ) ,但与非艾滋病感染者口腔黏膜癌前病变无明显差别 (P >0 .0 5 ) ;( 2 )艾滋病感染者口腔黏膜疣状肿块中 ,HPV感染率为 88.2 % ,明显高与非艾滋病感染者口腔黏膜癌前病变和口腔黏膜鳞癌 (P <0 .0 1)。没有检测到EBV、CMV病毒感染。结论 :艾滋病感染者口腔疣状肿块和HPV感染有关 ,存在抑癌基因突变和细胞过度增殖现象。     

口腔黏膜病

艾滋病感染者口腔疣状肿块人类乳头状瘤病毒感染与P53，Ki-67蛋白过度表达；口腔异常增生上皮PCNA及细胞核面积分层计数的临床意义；艾滋病毒感染患者口腔黏膜疣状肿块人类乳头状瘤病毒感染的分型研究；口腔黏膜下纤维性变临床分析；儿茶解毒冲剂与昆明山海棠片治疗烂糜型口腔扁平苔藓的临床比较。     

湖北地区HIV阳性人群口腔内HPV感染状况研究

目的：对HIV感染者口腔黏膜乳头状瘤病毒（HPV）感染进行研究,并对比其中女性宫颈的感染状况,了解湖北地区HIV感染者口腔内HPV感染的流行和分布,证实HPV与HIV之间及相关疾病的相互关系。方法：收集40例自愿接受检查的HIV感染者的一般情况,检测其CD4＋T细胞计数,并对受检者中的女性进行宫颈检测,使用PCR方法检测口腔及宫颈处HPV亚型,采用SPSS 17．0软件进行统计分析。结果：有1例（2．5％）患者检测出口腔HPV52型,10例女性患者（38．5％）在宫颈黏膜样本中检测出HPV感染,且有2例同时检测出2种以上HPV基因型。结论：HIV感染者口腔内HPV感染率远低于宫颈黏膜HPV感染率,两区域间HPV感染状况没有明显联系。     

口腔鳞癌中HPV16、18型感染和p53蛋白表达的检测研究

目的探讨人类乳头状瘤病毒(human papillomavirus, HPV)感染、p53蛋白表达在口腔鳞状细胞癌发生、发展中的作用与相互关系.方法采用聚合酶链反应(PCR)检测HPV16、18型DNA;采用免疫组织化学LSAB法检测p53蛋白产物在细胞核中的表达.结果口腔鳞癌组中HPV16、18 DNA总阳性率为48.89%(22/45),p53蛋白表达阳性率为62.22%(28/45).HPV16、18型感染组及p53蛋白过度表达组的平均生存期、生存率均低于无HPV感染组(P>0.05)及无p53过度表达组(P<0.05).结论 HPV16、18型感染、p53基因突变与口腔鳞癌的发生密切相关.口腔鳞癌患者的预后在一定程度上与HPV感染、p53表达状况有关.     

正常口腔黏膜和口腔鳞癌中人乳头瘤病毒感染率的研究进展

黏膜高危型HPV-16、HPV-18感染是宫颈癌的主要致病因素,且与口腔鳞癌的发生密切相关,但目前对口腔鳞癌中HPV的感染率和亚型的分布尚不十分清楚。作者系统查阅了目前已经发表的有关HPV在正常口腔黏膜或口腔鳞癌中感染率和亚型分布的文献资料,对正常口腔黏膜、口腔鳞癌中人乳头瘤病毒的感染率的研究进展进行了综述。     

人乳头状瘤病毒致口腔鳞癌发生的研究进展

人乳头状瘤病毒(HPV)感染与人类许多疾病有关,它与口腔鳞癌的关系也已受到关注.目前研究认为,高危型HPV的E6、E7蛋白分别作用于p53和Rb,继而影响其它调节因子,使细胞周期发生紊乱,引起细胞恶变.本文对人乳头状瘤病毒感染引起的细胞周期调节因子改变在口腔鳞癌发生发展过程中的作用机制作一综述.     

人乳头瘤病毒感染与口腔黏膜疾病

人乳头状病毒（human papillomavirus,HPV）是一类双链闭合环状DNA病毒,属于乳头状瘤病毒科,与人类疾病紧密相关,对它的研究已经持续了百年之久,但在口腔黏膜病领域尚属起步阶段。该文就口腔黏膜病的HPV感染情况、HPV+口腔黏膜病的发病机制、预防和治疗等问题的研究情况进行述评。     

人乳头状瘤病毒口腔鳞癌发生的研究进展

人乳头状瘤病毒（HPV）感染与人类许多疾病有关,它与口腔鳞癌的关系也已受到关注。目前研究认为,高危型HPV的E6、E7蛋白分别作用于p53和Rb,继而影响其它调节因子,使细胞周期发生紊乱,引起细胞恶变。本文对人乳头状瘤病毒感染引起的细胞周期调节因子改变在口腔鳞癌发生过程中的作用机制作一综述。     

人乳头状瘤病毒感染与儿童口腔黏膜良性上皮增生

目的 探讨儿童口腔黏膜良性上皮增生性病损与人乳头状瘤病毒(human papillomavirus，HPV)感染及其类型的关系。方法 选取四川大学华西口腔医学院病理科近10年30例儿童口腔黏膜良性上皮增生性病损的病例，复习其临床病理特征及切片，并采用免疫组织化学及原位杂交方法检测HPV共同抗原及其类型。结果 口腔鳞状细胞乳头状瘤(squamous cell papilloma，SCP)20例(66．7％)，尖锐湿疣(condyloma acuminatum，CA)6例(20．0％)，口腔黏膜局灶性上皮增生(focal epithelial hyperplasia，FEH)4例(13．3％)。HPV检测结果显示：HPV共同抗原阳性者占73．3％(22／30)，其中SCP占75．0％(15／20)，6例CA HPV共同抗原均为阳性，4例FEH中仅1例HPV共同抗原为阳性；HPV类型以高危型HPV16／18为主，占77．3％(17／22)，其次是HPV6和HPV11。结论 儿童口腔黏膜良性上皮增生性病损与HPV感染关系密切，病毒类型以高危型HPV16／18为主，其病毒类型是否与成人(以HPV6、11为主)不同尚待进一步研究。     

Detection of human papillomavirus DNA in benign oral squamous epithelial lesions in Venezuela

The polymerase chain reaction (PCR) was applied to the detection of human papillomavirus (HPV) infection in biopsies taken from clinically normal oral mucosa of 20 subjects and clinical lesions of 40 patients. PCR for HPV-DNA amplification was performed using consensus primers MYO9/MYO11 and subsequent typing for HPV of high and low oncogenic risk HPV types were identified by restriction enzyme analysis (restriction fragment length polymorphism, RFLP). The HPV viral genome was present in 55% (22/40) of the oral benign lesions (OBL) and in 10% (2/20) of the control samples. In the PCR+ OBL, we observed 90.9% of low oncogenic risk types (HPV-6 -13 and -32) and 9.1% of the samples had a mixed infection with low and high oncogenic types (HPV-6 and -16). In the control samples, we observed one patient with HPV-6 and another with HPV-6 and -16 in the same sample. All of the eight focal epithelial hyperplasia cases were positive for low risk HPV types (88% HPV-13 and 12.5% HPV-32). In conclusion, this study demonstrates a high incidence of HPV in oral benign lesions from Venezuelan patients.     

Design of a unique PCR primer for detection of oral HPV infection

Human papillomavirus (HPV) has been known as a pathogen of oral dysplasia. However, suitable PCR primers for the detection of oral HPV infection have not been reported. The aim of this study was to design unique consensus primers. The consensus primers were designed by homologues analyses between subtypes 2, 6, 11, 13, 16, 18, 30, 32 and 58, which frequently infect the oral membrane. PCR, with our designed primer, detected HPV DNA subtypes 2, 6, 11, 16, 18 and 58, and also showed PCR product from a clinical papilloma sample. These results indicate that our designed consensus primer can be used for the study of the relationships between oral disease and HPV infection.     

Oral and Genital Human Herpesvirus 8 and Human Papillomavirus in heterosexual partners

Background: The purpose of this study was to verify a possible co‐infection of human herpesvirus 8 (HHV‐8) in commonly associated human papillomavirus (HPV) penile lesions and to determine the frequency of detection of these viruses in the oral mucosa of their female counterparts. Methods: Thirty‐one male subjects underwent penile swabs from clinical HPV‐related lesions. Their female counterparts underwent swabs of the vagina, uterine cervix, and oral mucosa. HPV and HHV‐8 detection was performed by polymerase chain reaction using the consensus primers MY11/MY09 and KS1/KS2, respectively. Results: HPV DNA was detected in 31/31 penile lesions. HPV DNA was also detected in 18/31 (58%) female genital brushings and 17/31 (54%) female oral brushings. HHV‐8 DNA was detected in 1/31 (3.2%) male genital brushings and 3/31 (9.6%) female oral mucosa brushings. None of the female genital brushings were HHV‐8 DNA‐infected. Conclusions: Based upon the results of this study, co‐infection between HPV and HHV‐8 in malignant and pre‐malignant penile lesions is an unlikely finding.     

Human papillomavirus (HPV) types 2 and 57 in oral verrucae demonstrated by in situ hybridization

Twenty-one cases of verrucae vulgaris (oral warts) were investigated for human papillomavirus (HPV)-group specific antigen by immunocytochemistry and for HPV types 1, 2, 4, 6, 11, 16, 18 and 57 by DNA in situ hybridization with biotinylated probes. Twelve (57%) cases demonstrated the presence of HPV-group specific antigen. Fifteen (71%) cases showed the presence of HPV DNA, 13 of which (87%) demonstrated both HPV types 2 and 57 in the same cells and 2 of which (13%) demonstrated only HPV 2. Six cases were negative for HPV 2 and 57 and all 21 cases (100%) were negative for HPV types 1, 4, 6, 11, 16 and 18. Results indicate the association of a new and as yet unidentified HPV type, closely related to HPV 2 and 57, with oral warts. The identification of both cutaneous type HPV 2 and another type closely related to HPV 2 and 57 in oral verrucae on keratinized and non-keratinized mucosal surfaces indicates the possibility of a latent infection; three patients had a history of warts on their hands, suggesting autoinoculation. This study indicated that future investigations of oral warts, based on a correlation of clinical and histological features with HPV types by DNA in situ hybridization, are called for.     

Human papillomavirus as a risk factor in oral carcinogenesis: a study using in situ hybridization with signal amplification

Introduction:  It is still controversial whether human papillomavirus (HPV) can be considered a risk factor in oral carcinogenesis. The aim of this study was to detect HPV DNA in 50 cases diagnosed as oral leukoplakias, with different degrees of epithelial dysplasia, and as oral squamous cell carcinomas, using in situ hybridization with signal amplification (CSA-ISH).
Methods:  HPV DNA was assessed in paraffin sections using CSA-ISH with a wide-spectrum biotinylated DNA probe. In HPV-positive cases, genotyping with specific probes to HPV types 6/11, 16/18 and 31/33 was performed.
Results:  The overall prevalence of HPV infection was 24%, markedly higher than that found in the control group. Results showed a discrete proportional relationship in the indices found in leukoplakia with no dysplasia, leukoplakia with dysplasia, and squamous cell carcinoma, but this was not statistically significant. When separating the group of leukoplakia by degrees of dysplasia, this relation of proportion was not observed. In genotyping, HPV types 16/18 were the most prevalent, and types 6/11 were only found in groups of mild or no dysplasia.
Conclusion:  The results suggest that HPV is not likely to play a role in the progression of malignant transformation in oral lesions. Nevertheless, the increased prevalence of HPV infection compared to normal oral mucosa and the fact that high-risk HPV types were the most frequently identified do not allow the exclusion of HPV as a risk factor in oral carcinogenesis.     

Human papillomavirus and Epstein Barr virus in oral hairy leukoplakia among HIV positive Venezuelan patients

Oral hairy leukoplakia (OHL) is commonly found in individuals infected with HIV and represents the most frequent oral manifestation. The purpose of this study was to detect the presence of Human Papillomavirus (HPV) and Epstein Barr Virus (EBV) in OHL of HIV+ Venezuelan patients. We evaluated 21 HIV+ adult patients with clinically present OHL lesions: 11 under antiretroviral therapy, 10 without therapy, and 10 oral mucosal samples as controls. Nested-PCR was used to detect EBV and HPV infection. The INNO-LiPA HPV Genotyping v2 was applied to determine the HPV genotype. The EBV genome was found in 16/21 (76%) of the HIV+ patients with OHL. No difference was observed in EBV+ and EBV- patients related to antiretroviral therapy viral load and CD4+ Tcell coant. HPV-DNA was observed in 7/21 HIV positive cases (33%). The HPV genotypes detected were: 6, 11, 31, 33, 52, and 56/74. The most frequently HPV found was genotype 6 in 7/7, while two cases were HPV-11 and two HPV-52. Of the positive cases, 5/7 (71%) presented co-infection with more than one HPV genotype and 4/7 (57%) had HPV coinfection with high and low risk types. No case was EBV or HPV positive in the control group. In this study, a higher EBV prevalence was observed in OHL-HIV+ patients, confirming the etiologic role in this entity. A considerable number of cases were positive for HPV infection, and many patients presented coinfection with more than one HPV genotype as well as the presence of high oncogenic risk HPV in OHL.     

Human papillomavirus infection in cyclosporin-induced gingival overgrowth in renal allograft recipients.

BACKGROUND: Host immunity plays an important role in the development of human papillomavirus (HPV)-associated disease. The HPV infection in oral cyclosporin-induced gingival overgrowth in renal transplant recipients has not been investigated previously. The aim of this study was to establish the HPV infection of cyclosporin-induced gingival hyperplasia in renal transplant recipients through morphological changes and use of the in situ hybridization technique. METHODS: We examined 13 renal transplant recipient biopsies with gingival overgrowth lesions and 4 healthy mucosa samples of these patients. The histopathological diagnoses were established on the basis of widely accepted criteria, and the pathologist was not aware of the HPV result. An in situ molecular hybridization was carried out under low stringent conditions to detect HPV species with mixed biotin-labeled probes of HPV 6 and HPV 11, and under high stringent conditions with HPV 6, HPV 11, HPV 16, and HPV 18 probes for HPV typing. RESULTS: The HPV prevalence among the 13 samples studied was 92.31% (12/13), of which 4 tested positive for HPV 6-11 and 1 for HPV 16. The 4 biopsies of normal mucosa from gingival overgrowth patients were also reactive for HPV DNA. In 11/12 (91.7%) HPV-positive cases, koilocytotic atypia was found. CONCLUSIONS: The suppression of T-cell function by cyclosporin therapy can result in an increase of HPV infection, adding to the proliferative activity of cyclosporin in the oral mucosa.     

Human papillomavirus DMA in oral squamous cell carcinomas and normal mucosa

Human papillomavirus (HPV) infections in oral carcinomas and normal oral mucosa were studied by consensus primer screening and typing for HPV types 6/11,16 and 18 DNA. After polymerase chain reaction (PCR) the DNA species of interest were identified by Southern blot hybridization with digoxigenin-labeled oligonucleotide probes. Frozen tissue and scrapings were equally suitable for HPV testing and yielded high HPV detection rates in carcinomas. By comparison, HPV analysis of paraffin-embedded material was much less efficient. HPV were demonstrated in 61.5% (16/26) of oral squamous cell carcinomas, high risk HPV 16 and 18 being the preferential types. The frequency of HPV detection in non-neoplastic mucosa of tumor patients decreased clearly with increasing distance from the tumor (range 26.9–3.8%) suggesting focal HPV infections. In contrast, normal buccal mucosa of a group of healthy volunteers contained HPV DNA only in 1%(1/97).