口腔黏膜人乳头瘤病毒感染的研究现状

人乳头瘤病毒(HPV)在人类广泛传播,与许多人类常见病有关,已证实HPV感染是导致宫颈癌的主要病因。随着分子生物学技术的发展,已在多种口腔黏膜病损中检测出不同型别的HPV感染,越来越多研究表明HPV可能是引起多种口腔病损的致病因素。HPV在口腔黏膜的感染情况及其引起的口腔黏膜病损日益受到关注。本文对HPV的生物学特性、口腔黏膜HPV感染的途径、检测方法、HPV相关口腔黏膜损害及其可能的致病机制等进行综述。     

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。     

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。     

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。     

桂林地区口腔黏膜白斑中人乳头瘤病毒的检测

目的:探讨桂林地区口腔黏膜白斑与人乳头瘤病毒(HPV)亚型的关系。方法:运用PCR-反向斑点杂交法,检测桂林地区15例口腔黏膜白斑患者和21例正常口腔黏膜标本的DNA,对两组的阳性率进行χ2检验。结果:口腔黏膜白斑组,15例病人5例HPV呈阳性,均为16型。21例正常口腔黏膜标本中,4例HPV呈阳性,均为16型。两组比较,χ2=0.3429,P>0.05。结论:口腔黏膜白斑的发生与HPV无确切关系,但不排除HPV是口腔黏膜白斑的发病因素之一。     

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。     

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。     

口腔鳞状细胞癌高危型人乳头状瘤病毒感染的检测

目的 观察口腔鳞癌及口腔粘膜高危型人乳头状瘤病毒（HPV）感染情况,探讨HPV感染与临床及病理资料的关系。方法 用多聚酶链反应（PCR）检测73例口腔鳞癌及40例正常口腔粘膜石蜡包埋组织中HPV16、HPV18的DNA。统计分析其与临床及病理资料的关系。结果 口腔鳞癌HPV16／HPV18 DNA阳性率为74％（54／73）,正常口腔粘膜为55％（22／40）。口腔鳞癌与正常口腔粘膜HPV阳性率存在显著性差异（P＝0．040）。统计分析显示：HPV感染与患者的性别、年龄有关,与其它因素（肋瘤发生部位、嗜烟酒情况、肿瘤病理分级、临床分期）无关。结论 高危型HPV感染与口腔鳞癌的发生有关。口腔粘膜中HPV感染普遍存在,提示HPV在口腔肿瘤的发生中并非独立发挥作用。     

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.     

PL7Oral viral infections that could be transmitted oro‐genitally

Orogenital transmission has been suggested for several viruses, e.g. herpes simplex virus‐1 and ‐2 (HS‐1 and HSV‐2), Epstein‐Barr virus (EBV), cytomegalovirus (CMV), human herpesvirus‐8 (HHV‐8), human papillomavirus (HPV) and HIV. Most studies have focused on HIV, HSV and HPV. Unprotected orogenital contact, especially receptive oral intercourse, is associated with greater risk of HIV transmission than previously thought. Factors potentially associated with increased risk of HIV transmission through oral sex include poor oral health, the salivary anti‐HIV properties such as peroxidases and thrombospondin‐1, the local and systemic immunological responses, concomitant sexually transmitted infections, ejaculation in the mouth, local mucosal integrity, and the level of infectious HIV present at the oral mucosa. The probability of per act transmission in oral intercourse with ejaculation is 0.04%. HSV‐2 has been regarded as a sexually transmitted virus while HSV‐1 is causing primary herpetic gingivo‐stomatitis, muco‐cutaneous oro‐facial disease and ocular disease. Also HSV‐2 might be detected occasionally in oro‐facial area. Recent data on young women with a primary genital infection indicate that HSV‐1 is much more frequent than HSV‐2. Oro‐genital route of transmission is more common than expected in genital HSV‐1 infections. EBV is a tumorigenic herpes virus that is carried as a persistent infection by more than 90% of adults. Most persistently infected people produce EBV in their saliva, and transmission is through close contact. There is a significant association between sexual intercourse and EBV seropositivity, increasing with numbers of sex partners. Because EBV has been found in genital secretions from healthy seropositive men and women, direct spread of virus during sexual intercourse is possible. Today, 106 HPV types have been sequenced of which almost 40 have been detected also in oral mucosa, causing benign epithelial lesions (papillomas, condylomas, warts and focal epithelial hyperplasia, or FEH). Recent meta‐analyses of the case‐control studies have confirmed HPV as an independent risk factor for oral SCC with odds ratios (OR) 3.7 to 5.4. HPV16 is the overwhelmingly most frequent type. HPV has been regarded as a sexually transmitted disease but this view is challenged by frequent detection of HPV in children. Unlike in genital tract, natural history of oral HPV infection is poorly studied. As part of the Finnish HPV Family Study we evaluated natural history of oral HPV in within family members. The detection rate of HR HPVs varied from 15% to 27%. Our results indicate that natural history of HPV infection in oral mucosa mimics that of genital HPV infections. Oral sex had no association to oral HPV infection, but a persistent oral HPV infection of the spouse increased the risk of persistent oral HPV infection in the other spouse 10‐fold.     

Acetowhite staining and its significance in diagnosis of oral mucosal lesions in women with genital HPV infections

White staining of genital mucosa after acetic acid application (3-5%) (acetowhiteness) has been commonly regarded as a sign of HPV infection, and acetic acid application is widely used as a routine diagnostic means to screen the HPV infections. However, the sensitivity and specificity of acetowhite staining to detect HPV infections has not been properly studied. The usefulness of acetic acid application in detecting oral HPV infections is not established. In this communication, the oral mucosal changes after acetic acid application were systematically recorded in 315 women prospectively followed-up for genital HPV infections, with special reference to smoking, alcohol consumption, histology, cytology and presence of HPV DNA. Strong and weak acetowhite staining were found in 2% and 38% of the patients, respectively. The mean age of these patients was 30.8 yr in contrast to 37.3 yr of the patients without acetowhite lesions, the difference being significant. In most cases, the staining was widely distributed over the buccal mucosa. Acetowhiteness on oral mucosa was seen significantly more frequently in smokers, but the staining did not show any correlation with alcohol consumption, histologic and cytologic findings, presence of HPV DNA or with glycogen content. The specificity of acetowhite staining to detect HPV DNA was 50%. Vacuolized cells were found significantly more often in PAS-positive biopsies. The mean day of the menstrual cycle of the acetic acid--positive and -negative patients at examination was 14.9 and 11.9, respectively. The results suggest that positive acetic acid staining in oral cavity should not be regarded as a diagnostic criteria for HPV infection.(ABSTRACT TRUNCATED AT 250 WORDS)     

Human papillomavirus (HPV) infections and their associations with oral disease

More than 65 distinct types of human papillomavirus (HPV) have been identified to date. Several of the HPV types have been proposed as etiologic agents of squamous cell carcinoma. In the oral cavity, HPVs have been found associated with several benign squamous cell proliferations. Evidence from histology and DNA hybridization studies suggests that HPV is also involved in oral carcinogenesis. It is apparent, however, that substantial amount of confusion exists in the diagnosis of oral HPV infections. The keratotic, papillary lesions in the oral cavity are usually small and easily overlooked. The gross appearance of these viral lesions is not distinct enough to be readily diagnosed by the clinicians. Degenerative changes found on oral mucosa frequently simulate koilocytosis. Thus, caution should be exercised to avoid overdiagnosis of HPV infection in the oral cavity. The present review summarizes the current evidence available on HPV infections in general and on oral HPV infections in particular. The diagnostic techniques available as well as the problems encountered in the distinction of these lesions are also discussed in short.     

Human papillomavirus infection and its association with HIV

Human papillomavirus (HPV) can infect oral mucosa, causing asymptomatic infection or warty lesions. Several case-control studies have confirmed HPV as an independent risk factor for squamous cell carcinoma. HPV-related cancers seem to have better prognoses and different risk factors than do HPV-negative ones. HIV-infected patients are known to be at increased risk for persistent genital and anal high-risk HPV infections and intraepithelial neoplasm. Since the era of highly active antiretroviral therapy, the prevalence and persistence of warty lesions in oral mucosa have increased. Oral squamous cell carcinoma was recently added in the case definitions for common HIV-related oral mucosa lesions. The increased risk of HPV infection in HIV patients has been associated with impaired immune response to HPV, highly active antiretroviral therapy, aging of the HIV-infected patients, and direct interaction between the 2 viruses. HPV32 seems to be much more prevalent in asymptomatic HPV infections and warts among those infected with HIV than among those in the general population. Regarding HIV genes, there is evidence of an interaction between HPV and tat, rev, and vpr. HIV might play a role in HPV-associated pathogenesis by exhorting oncogenic stimuli via tat and rev or visa versa.     

Dot blot hybridization in detection of human papillomavirus (HPV) infections in the oral cavity of women with genital HPV infections

The presence of human papillomavirus (HPV) types 2, 6, 7, 11, 13 and 16 DNA in cytologic scrapings of oral mucosa was studied in 309 women with genital HPV infections. The objective was to test the usefulness of oral mucosal scrapings (3 sequential swabs) in HPV DNA detection by dot blot hybridization. Based on hybridization with the 32P-labelled Alu-repeat probe, most samples contained more than 10(5) cells, which is an adequate number of cells for dot blot hybridization. Hybridization with 32P-labelled HPV DNA probes showed that 3.8% of the 309 women had an oral HPV infection. Of these, only 2 had clinical lesions indicative of HPV. All other oral HPV positive subjects had clinically healthy mucosa. HPV 6 was the most common (3.1%) type, followed by HPV 11 and 16 (1.1%). In 3 cases the genital mucosa harboured the same HPV type as found in the oral cavity. The results indicate that oral mucosal scraping results in adequate number of cells for dot blot hybridization with HPV DNA. Although the method is likely to result in an underestimation of latent and subclinical HPV infections, it is useful for studying the clinical HPV infections as well as other viral infections known to be present in exfoliated cells.     

Low prevalence of human papillomavirus infection in the healthy oral mucosa of a Northern Italian population

J Oral Pathol Med (2012) 41 : 16–20 Background: Oral cancer is the sixth most common malignancy in developed countries, representing almost 3% of malignant tumors. Tobacco use and alcohol consumption are well‐established risk factors. However, the observation that most patients with oral cancer have not been exposed to these risk factors suggests that additional causes may promote oral carcinogenesis. A link has been suggested between human papillomavirus (HPV) and oral cavity cancer but the significance of HPV contribution to oral carcinogenesis as well as the prevalence of HPV infection in normal oral cavity mucosa remains debated. Methods: In this study, the prevalence of oral HPV infection was evaluated in 81 randomly selected Northern Italian subjects with clinically normal oral mucosa using a nested PCR on DNA extracted by oral smears. Results and conclusions: No HPV‐related lesions were detectable in any of the smears analyzed by cytological approach. nPCR identified HPV DNA in only one (1.2%) of the specimens obtained from clinically healthy oral mucosa and subsequent characterization assigned the positive case to HPV type 90. These data suggest that the incidence of HPV infection in the healthy population might be very low and that other risk factors are likely responsible to promote oral carcinogenesis.     

WHO is in and WHO is out of the mouth,salivary glands,and jaws sections of the 4th edition of the WHO classification of head and neck tumours

This review of changes to the 4th edition of the WHO classification of head and neck tumours focuses on their impact on the surgical care of diseases that affect the salivary glands, jaws, and oral cavity. Updates to the chapter on the salivary glands include the addition of secretory carcinoma and sclerosing polycystic adenosis. The odontogenic cysts are back, and the odontogenic keratocyst is listed among them, as it has now lost its brief and confusing designation as a neoplasm. The newly-defined sclerosing odontogenic carcinoma and primordial odontogenic tumour have been added. Oropharyngeal tumours have been separated from those of the oral cavity, which reflects the importance of HPV in carcinoma of the tonsils. The problems of grading oral epithelial dysplasia persist.     

Human papillomavirus (HPV): making the case for ‘Immunisation for All’

Human papillomavirus (HPV) contributes to the most common sexually transmitted infections, with repeated and persistent infection with particular types causing disease in both men and women. Infection with low‐risk HPV types can lead to genital warts and benign lesions of the oral cavity, while high‐risk types can cause various HPV‐related malignancies. The incidence of head and neck cancers has been rising in the past number of decades mostly due to oropharyngeal cancer linked to HPV infection. HPV vaccination has been shown to be effective for cervical and other anogenital HPV‐related cancers, and there is significant potential for HPV vaccination to prevent oropharyngeal cancers, given that the HPV types implicated in this disease can be protected against by the HPV vaccine. Few countries have implemented a universal HPV vaccination programme for males and females, with many countries arguing that female‐only vaccination programmes protect males via herd immunity and that men who have sex with men will be protected via targeted vaccination programmes. We argue these may be limited in their effectiveness. We propose that the most effective, practical, ethical and potentially cost‐effective solution is universal HPV vaccination that might lead to control of HPV‐related diseases in men and women alike.     

Association between proliferative verrucous leukoplakia and infection with human papillomavirus type 16

Proliferative verrucous leukoplakia (PVL) is a recently described clinical entity characterized by multifocal oral lesions that frequently progress to oral cancer despite abstinence from tobacco use by most patients. To determine if this condition is associated with human papillomavirus (HPV), a polymerase chain reaction (PCR) for HPV DNA was performed on 9 lesions from 7 patients with PVL, histologically diagnosed with focal keratosis (1), papilloma (1), epithelial dysplasia (5) and squamous cell cancer (2). Eight (89%) were HPV positive, 7 for HPV 16. For comparison, we studied 55 non-PVL-associated oral specimens, including 24 oral squamous cell cancers. Of the cancers, 8 (33%) were HPV positive, 4 for HPV 16. These data suggest that HPV 16 infection may play an important role in the pathogenesis of PVL-associated oral dysplasia and possibly cancer, but is found in only a small proportion of the more common, non-PVL associated-oral lesions.