Human papillomavirus DNA detection in women with primary abnormal cytology of the cervix: prevalence and distribution of HPV genotypes

OBJECTIVES: In this study, we focus on the prevalence and occurrence of different anogenital human papillomavirus (HPV) genotypes in a first abnormal cervical screening test, and correlate HPV genotyping with the cytological diagnosis on thin-layer liquid-based preparations in routine gynaecological screening. METHODS: Out of 780 abnormal smears, 513 tested positive for HPV. All 25 different HPV types were identified by Line Probe Assay. RESULTS: The prevalence of high-risk HPV types increased from 72% in atypical squamous cell of undetermined significance to 94.5% in high-grade intra-epithelial lesion (HSIL). Co-infection with multiple HPV types was predominantly found in HSIL (35.8%). In the HSIL group the most common HPV types were 16, 52, 51 and 31; type 18 was rarely present. CONCLUSION: The role of types 31, 51 and 52 should be considered in future studies on vaccine development.     

Human papillomavirus (HPV) type 50, a type associated with epidermodysplasia verruciformis (EV) and only weakly related to other EV-specific HPVs.

The cloning and partial characterization of the genome of human papillomavirus type 50 is presented. Alignment of the genomic map with that of human papillomavirus type 5, with which it is only weakly related, was permitted by partial DNA sequence analysis.     

川西高原地区妇女人乳头瘤病毒感染现状及其与阴道微环境改变的关系

【背景】人乳头瘤病毒(human papillomavirus,HPV)感染与宫颈癌及癌前病变的发生密切相关,HPV疫苗是预防感染的重要手段,但HPV亚型分布具有明显的区域差异。【目的】了解川西高原地区妇女宫颈HPV感染现状,探讨其与阴道微环境改变之间的关系,为该人群HPV疫苗使用和宫颈癌预防工作提供指导。【方法】选取2017年11月至2019年5月在成都三六三医院体检和就诊的3 816例川西高原地区妇女,进行HPV基因分型、薄层液基细胞学检测(thinprep cytologic test,TCT)和阴道微环境检查,分析HPV感染率和基因型分布,并探讨高危型HPV (high risk HPV,hrHPV)感染与阴道微环境改变之间的关系。【结果】3 816例妇女的HPV总感染率为19.81%(756/3 816),hrHPV感染率为16.48%(629/3 816),HPV52在hrHPV感染中占比最高,达17.20%(135/785),后面依次为HPV58 (92/11.72%)、HPV16 (89/11.34%)、HPV53 (88/11.21%)、HPV18 (55/7.01%...     

Human papillomavirus (HPV) infection in Southern Africa: prevalence,immunity, and vaccine prospects

Human papillomavirus (HPV) associated cancers are more prevalent in developing countries compared to developed countries. The major cancer caused by HPV is cervical cancer. The humoral immune response to HPV can be a marker of past infection but may also reflect persistent infection and cervical disease. IgA antibodies to HPV in oral fluid were also found to be markers of cervical disease. Cell mediated immunity is important in clearing HPV infection and for regression of the associated lesions: this means that women infected with HIV have a high prevalence of co-infection with HPV. Good cervical screening programmes can control HPV associated cervical neoplasia. However, in countries such as South Africa, where these programmes are inadequate, there is a need for an HPV vaccine. The development of HPV vaccines is reviewed. There is a call for an inexpensive vaccine that will be accessible to the women that do not have access to adequate screening programmes and are therefore at the greatest risk of cervical cancer.     

Prevalence of human papillomavirus (HPV) type 16 variants and rare HPV types in the central Amazon region

Infection by human papillomavirus (HPV) is one of the primary causes of mortality by cancer in northern Brazil. Sexually active women from Manaus, Amazonas, without cytological alterations and women with pre-malignant and malignant cytological alterations were examined for HPV virus, identified via PCR and sequencing. The target region for this study was part of the L1 capsid gene of HPV. Twenty-three samples that were PCR-positive were sequenced. Analysis of 336 bp demonstrated a high incidence of high-risk HPV types in the population of Manaus, identified as HPVs 16, 33, 58, 66, 68. HPV type 16 was the most prevalent, presenting two variants similar to the Asian-American (AA) and East-Asian type (As) variants. A rare HPV type 13 related to "Heck's disease" was also detected. This preliminary provides important information about the HPV circulating in Amazonas State.     

中国大陆女性HPV感染危险因素的Meta分析

了解评价中国大陆女性HPV感染的相关危险因素, 为预防和控制提供参考依据。

采用系统评价法综合评价1995年1月1日至2020年12月31日在PubMed、CNKI、VIP和WanFang数据库收录的所有关于中国女性人群中发表的有关HPV感染相关危险因素的相关研究。由2位研究者独立筛选文献、提取数据资料和评价纳入研究的文献质量后, 采用Stata 12.0软件进行分析。

共有48篇文献纳入研究, 总人数为210 009人, HPV感染病例26 653例, 分析模型结果显示: 孕次 > 1次为1.14(1.07~1.20), 产次 > 1次为1.35(1.06~1.74), 流产次数 > 1次为1.30(0.97~1.74), 避孕药为1.11(0.91~1.34), 避孕套为0.56(0.35~0.89), 宫内节育器避孕为1.02(0.91~1.13), 滴虫性阴道炎为1.33(1.04~1.69), 宫颈糜烂为2.2(1.03~4.70), 吸烟为1.28(1.09~1.51), 饮酒为1.15(1.07~1.24), 文化程度初中及以下为1.03(0.74~1.44), 无工作为0.94(0.73~1.21), 已婚为0.60(0.47~0.78), 结婚次数 > 1次为1.47(1.25~1.73), 性伴侣数 > 1个为1.96(1.46~2.62), 丈夫婚外性行为1.68(1.35~2.09), 丈夫性伴侣数 > 1个为2.14(1.45~3.15), 性生活频率 > 2次/周为1.37(0.79~2.37), 绝经为1.65(1.11~2.46), 初次性生活年龄≤20岁为1.48(1.23~1.78)。

HPV感染主要危险因素为多孕, 多产, 滴虫性阴道炎, 宫颈糜烂, 吸烟, 饮酒, 结婚次数过多, 多个性伴侣, 丈夫婚外性行为, 丈夫有多个性伴侣, 绝经, 初次性生活年龄过早, 而避孕套和已婚是其保护因素。

     

High-risk human papillomavirus (HPV) in parotid lesions

Although several studies have reported that oropharyngeal infection with HPV may predispose to tumorigenesis, little is known about the etiological factors of salivary gland tumors and the presence of HPV. We studied 9 parotid lesions for HPV infection including an oncocytoma, an acinic cell carcinoma, a high-grade adenocarcinoma, a low-grade polymorphous adenocarcinoma, a Warthin's tumor and 2 pleomorphic adenomas, a lymphoepithelial cyst and a lipoma of the parotid gland. DNA was extracted from formalin-fixed and paraffin-embedded tissue sections. Solution PCR for HPV detection was performed using the GP5+/GP6+ primers, while HPV typing was carried out by multiplex PCR for HPV6, 11, 16, 18, and 33; positive samples were recorfirmed by PCR with specific primers for each type. Quantitative real-time PCR for the high-risk HPV genotypes 16, 18, 31, 33, 35, 52, 58 and 67 was also performed to quantitate the viral load. Finally, in situ PCR was employed with HPV16-specific primers by direct-detection method. Seven of the 9 parotid lesions were HPV positive while 6 of these 7 had been infected by HPV16 and/or HPV18 oncogenic types. High viral load of highrisk genotypes of HPV was found in the oncocytoma, in one of the pleomorphic adenomas, and in the Warthin's tumor. Finally, in situ PCR indicated that HPV16 amplification occurred in the salivary gland tumors. This is the first time that highrisk HPV genotypes are detected in these histological types of parotid lesions, suggesting the possible involvement of the virus in the disease.     

Cervical secretory immunoglobulin A to human papillomavirus type 16 (HPV16) from HPV16-infected women inhibit HPV16 virus-like particles-induced hemagglutination of mouse red blood cells

Secretory immunoglobulin A (sIgA) antibodies are the first line of defence at the genital mucosa, and are thought to hinder viral infections by binding to conformational epitopes on the viral capsid. To investigate if cervical sIgA binds to conformational epitopes of the Human papillomavirus type 16 (HPV16), cervical mucus samples from 109 HPV16-infected patients were examined in a HPV16 virus-like particles-induced hemagglutination inhibition assay. 48 (44.1%) patients were able to inhibit hemagglutination. Inhibition of hemagglutination was associated with the presence of sIgA (P=0.001). In conclusion, naturally occurring cervical anti-HPV16 sIgA binds to and hinders conformational epitopes on the viral capsid, suggesting that these antibodies might have a neutralizing capacity.     

cis-Acting components of human papillomavirus (HPV) DNA replication: linker substitution analysis of the HPV type 11 origin.

Papillomavirus DNA replication requires the viral trans-acting factors E1 and E2 in addition to the host cell's general replication machinery. The origins of DNA replication in bovine and human papillomavirus genomes have been localized to a specific part of the upstream regulatory region (URR) which includes recognition sites for E1 and E2 proteins. To fine map cis-acting elements influencing human papillomavirus type 11 (HPV-11) DNA replication and to determine the relative contributions of such sites, we engineered consecutive linker substitution mutations across a region of 158 bp in the HPV-11 origin and tested mutant origins for replication function in a cell-based transient replication assay. Our results both confirm and extend the findings of others. E2 binding sites are the major cis components of HPV-11 DNA replication, and there is evidence for synergy between these sites. Differential capacity of the three E2 binding sites within the origin to affect replication may be attributed, at least in part, to context. At least one E2 binding site is essential for replication. The imperfect AT-rich palindrome of the E1 helicase binding site is not essential since replication occurs even in the absence of this sequence. However, replication is enhanced by the presence of the palindromic sequence in the HPV-11 origin. Sequence components adjacent to the E1 and E2 binding sites, comprising AT-rich and purine-rich elements and the consensus TATA box sequence, probably contribute to the overall efficiency of replication, though they are nonessential. None of the other cis elements of the HPV-11 origin region analyzed seems to influence replication significantly in the system described. The HPV-11 origin of DNA replication therefore differs from those of the other papovaviruses, simian virus 40 and polyomavirus, inasmuch as an intact helicase binding site and adjacent AT-rich components, while influential, are not absolutely essential.     

A retrospective analysis of human papillomavirus (HPV) prevalence and genotype distribution among 25,238 women in Shanghai,China revealed the limitations of current HPV-based screening and HPV vaccine

BackgroundTo determine the human papillomavirus (HPV) type-specific prevalence and distribution among women with various age and cervical lesions in Shanghai, China. And to evaluate the carcinogenicity of different high-risk HPV (HR-HPV) and the efficacy of HR-HPV testing and HPV vaccine.MethodsThe clinical data from 25,238 participants who received HR-HPV testing (HPV GenoArray test kit, HybriBio Ltd) at the Affiliated Hospital of Tongji University from 2016 to 2019 were reviewed and analyzed using SPSS (version 20.0, Tongji University, China).ResultsThe overall prevalence of HPV was 45.57% in the study population, of which 93.51% were found HR-HPV infection. The three most prevalent HR-HPV genotypes were HPV 52 (22.47%), 16 (16.4%) and 58 (15.93%) among HPV-positive women, and HPV 16 (43.30%), 18 (9.28%) and 58 (7.22%) in women with histologically confirmed cervical cancer (CC). 8.25% of CC were found to be HPV negative. Only 83.51% of CC cases were related to the HPV genotypes covered by nine-valent HPV vaccine. HPV prevalence and genotype distribution varied with age and cervical histology. The odds ratios (OR) of HR-HPV for CC were also different, among which the top three types were HPV 45 [OR= 40.13, 95% confidence intervals (CI) 10.37–155.38], 16 (OR=33.98, 95%CI 15.90–72.60) and 18 (OR=21.11, 95%CI 8.09–55.09). The increase in the types of HPV infection did not increase the risk of CC correspondingly. As the primary cervical screening method, HR-HPV testing showed the high sensitivity (93.97%, 95%CI 92.00–95.49) but low specificity (42.82%, 95%CI 41.81–43.84).ConclusionsOur study provide the comprehensive epidemiological data on HPV prevalence and genotype distribution among Shanghai women with various cervical histology, which can not only serve as a significant reference for clinical practice, but also implicated the need of more effective CC screening methods and HPV vaccine covering more subtypes.     

Induction of an antibody response in mice against human papillomavirus (HPV) type 16 after immunization with HPV recombinant Salmonella strains

 Human papillomaviruses (HPV) are present in approximately 95% of all cervical carcinomas and the HPV E6 and E7 genes are continuously expressed in these lesions. There is also circumstantial evidence that often natural immunity against HPV is generated and that this is of influence on HPV-induced lesions. Stimulation of the immune system by proper presentation of relevant HPV antigens might, therefore, lead to a prophylactic or therapeutic immunological intervention for HPV-induced lesions. For this purpose we have expressed the E6 and E7 protein of HPV 16 in an attenuated strain of Salmonella typhimurium (SL3261, aroA mutation), which has been used extensively as a live vector. Live recombinant Salmonella vaccines have the ability to elicit humoral, secretory and cell-mediated immune responses, including cytotoxic T cells, against the heterologous antigens they express. This report describes the construction of recombinant Salmonella strains expressing the HPV 16 E6 and E7 proteins, and the induction of an HPV-16-specific immune response in mice after immunization with these live vectors. Received: 25 June 1996 / Accepted: 6 August 1996     

Preclinical model to test human papillomavirus virus (HPV) capsid vaccines in vivo using infectious HPV/cottontail rabbit papillomavirus chimeric papillomavirus particles

A human papillomavirus (HPV) vaccine consisting of virus-like particles (VLPs) was recently approved for human use. It is generally assumed that VLP vaccines protect by inducing type-specific neutralizing antibodies. Preclinical animal models cannot be used to test for protection against HPV infections due to species restriction. We developed a model using chimeric HPV capsid/cottontail rabbit papillomavirus (CRPV) genome particles to permit the direct testing of HPV VLP vaccines in rabbits. Animals vaccinated with CRPV, HPV type 16 (HPV-16), or HPV-11 VLPs were challenged with both homologous (CRPV capsid) and chimeric (HPV-16 capsid) particles. Strong type-specific protection was observed, demonstrating the potential application of this approach.     

Human papillomavirus type 48.

The cloning and partial characterization of the genome of human papillomavirus (HPV) type 48 is presented. Hybridization and short DNA sequence analyses permitted the alignment of the genome to the HPV genetic map.     

人乳头瘤病毒16型L1蛋白的克隆及表达

采用PCR技术从宫颈癌组织中扩增人乳头瘤病毒16型(Human papillomavirus type16,HPV16)L1全长基因片段,目的片段克隆到pMD18T载体后经酶切鉴定及测序确认。构建重组原核表达质粒pGEX4T1-L1,转化大肠杆菌E.coliBL21,IPTG诱导表达出以非可溶性蛋白形式存在的表达蛋白,该重组蛋白的表达量占菌体总蛋白的17%,免疫印迹检测表明,表达蛋白与宫颈癌病人血清出现特异性反应。成功构建了重组原核表达质粒pGEX4T1-L1,并且在原核细胞中得到表达,为进一步研究L1蛋白的免疫学活性及疫苗的研发奠定了基础。     

Human papillomavirus type 53.

The cloning and partial characterization of the genome of human papillomavirus type 53 is presented. The virus is a distinct type and is most closely related to human papillomavirus type 30.     

Human papillomavirus type 29 (HPV-29), an HPV type cross-hybridizing with HPV-2 and with HPV-3-related types.

The cloning and partial characterization of human papillomavirus (HPV) type 29 is presented. By hybridization analyses, this virus appears to be related to HPV types associated with common warts and HPV types associated with flat warts.     

HLA types in women with cervical human papillomavirus (HPV) lesions prospectively followed up for 10 years

Certain genotypes of HPV have been recently implicated in the etiology of carcinoma of the uterine cervix. In order to determine whether HLA antigen‐controlled immunoregulatory functions have a role in the pathogenesis of HPV infections, class I and II HLA antigen typing was carried out on a series of 96 randomly selected women who were part of a cohort of 530 women prospectively followed up for cervical HPV infections in our clinic since 1981. The frequency of the DQ3 antigen, which has previously been reported to be increased among cervical cancer patients, was decreased in our HPV patients compared with the control group of Finnish women, but it was slightly increased in HPV16‐infected women ( P =0.0812). However, we were able to demonstrate that HLA‐DR5 antigen is significantly increased (i) in patients with high grade cervical intraepithelial neoplasia (CIN) ( P <0.02), and (ii) in women harbouring the high risk HPV type 16 ( P =0.0003), thus confirming earlier reports of an association of this HLA antigen and cervical cancer. Such a close association between the high risk HPV type 16 with an HLA antigen might have important implications in the possible immunogenetic basis of the increased risk for squamous cell carcinoma of the uterine cervix.     

Replication of human papillomavirus (HPV) DNAs supported by the HPV type 18 E1 and E2 proteins.

Transient replication of human papillomavirus (HPV) type 18 DNA was shown to require the viral E1 and E2 proteins. A 108-bp sequence within the long control region (nucleotides 12 to 119) was sufficient to function as the origin, but maximal replication required a region of 177 bp from positions 7800 to 7857 and 1 to 119 of HPV-18. The E1 and E2 proteins of HPV-18 also supported transient replication of plasmids containing the origins of HPV-1a and bovine papillomavirus type 1 to low levels. Interestingly, the level of replication observed with the HPV-6b origin was higher than that obtained with the homologous HPV-18 origin.