Disease Markers23(2007)273–281273 IOS Press
HPV detection methods
Antoinette A.T.P.Brink,Peter J.F.Snijders and Chris J.L.M.Meijer?
VU University medical center,Department of Pathology,Section Molecular Pathology,De Boelelaan1117,1081 HV Amsterdam,The Netherlands
Abstract.Given the causal relation between a persistent high-risk human papillomavirus(hrHPV)infection and the development of high-grade cervical intraepithelial neoplasia(CIN)and cervical cancer,hrHPV testing has been advocated in addition to cytology for the detection of clinically relevant cervical lesions.HrHPV testing is thought to improve cervical screening algorithms,the management of women with cytologically equivocal smears,and the management of women treated for high grade CIN.In this chapter we discuss different methods for HPV detection and genotyping and their respective applications. Keywords:Human papillomavirus,polymerase chain reaction,reverse hybridization,hybrid capture,real-time PCR,cervical carcinoma,NASBA,DNA probes,epidemiology
1.Introduction
Cervical cancer is preceded by premalignant lesions termed cervical intraepithelial neoplasia(CIN).Cervi-cal cancer screening largely relies on cytological detec-tion of these premalignant lesions,which can be treated relatively easily and with minor side effects.Given the causal relation between a persistent high-risk human papillomavirus(hrHPV)infection and the development of high-grade CIN and cervical cancer,hrHPV testing has been advocated in addition to cytology for the de-tection of clinically relevant cervical lesions.HrHPV testing is thought to improve cervical screening algo-rithms[1],the management of women with cytologi-cally equivocal smears[2,3],and the management of women treated for high grade CIN[4].In this chapter we elaborate on the different methods for HPV detec-tion and their respective applications.
1.1.HPV phylogeny
HPVs are associated with various benign and malig-nant epithelial proliferative diseases.Over100geno-
?Corresponding author:Prof.Dr.C.J.L.M.Meijer,Dept.Pathol-ogy,VU University medical center,PO Box7057,1007MB Amster-dam,The Netherlands.Tel.:+31204444070;Fax:+31204442964; E-mail:cjlm.meijer@vumc.nl.types of HPV are recognized.An HPV isolate is de-scribed as a novel type if the nucleotide sequence of its E6,E7and L1genes differs more than10%from that of any other HPV type.Based on tropism,a distinction can be made between cutaneous HPV types that infect the epidermis,and mucosal HPV types that infect the epithelia of the anogenital or the aerodigestive tract. In vitro studies showed that a group of phylogenet-ically related mucosal HPV types have oncogenic po-tential:their E6and E7proteins interfere with cell cy-cle regulation by mediating degradation of p53and pRb proteins,respectively[5,6].Exactly these HPV types are an important causal factor in carcinogenesis of the uterine cervix and are therefore designated“high-risk”(hr)[7].Epidemiological studies have shown that these hrHPVs include types16,18,31,33,35,39,45,51,52, 56,58,59,68,73and82,and probably also types26, 53and66[8].In the phylogenetic tree of HPV types, hrHPVs cluster in the groups designated A5,A6,A7, A9and A11[9].Non-oncogenic or low-risk genital HPVs(lrHPVs)are phylogenetically distant from the hrHPVs.They include HPV6,11,40,42,43,44,54, 61,70,72,81,and CP6108.Their E6and E7pro-teins are less competent in interfering with p53[10] and pRb[11]functions than the E6and E7proteins of hrHPVs.LrHPVs can cause benign proliferations such as condylomata acuminata(genital warts).For a number of mucosal HPV types,the risk has not been
ISSN0278-0240/07/$17.00 2007–IOS Press and the authors.All rights reserved
274 A.A.T.P.Brink et al./HPV detection methods
determined yet[8].However,some of them could be considered as potentially oncogenic due to their phylo-genetic relationship with known hrHPV types.For ex-ample HPV type67,which initially was isolated from a vaginal intraepithelial neoplasia(VIN)[12],clusters in the A9group that contains only hrHPVs such as HPV16[9].
1.2.The need for HPV genotyping
Many HPV tests rely on cocktails of probes repre-senting13or14of the most common hrHPV types. It has been suggested that the added value of less fre-quent hrHPV types to such probe cocktails would be small,probably irrelevant for screening programs,and resulting in a substantial decrease in screening speci-?city[13,14].However,the increasing need to distin-guish individual hrHPV types is illustrated by sever-al current developments in the?eld of HPV research. Firstly,there is growing evidence that certain hrHPV types confer increased risks for high-grade CIN and cervical carcinomas.This is discussed in more detail in the next paragraph.Secondly,20–30%of HPV in-fections involve multiple HPV types and in those cas-es typing is necessary to determine the contribution of the individual HPV types.Thirdly,there is an increas-ing interest in prophylactic HPV vaccination(reviewed in[15]),which entails studies of geographical distri-bution of HPV types and their associated diseases as a basis for prophylactic vaccination programs.Once vaccination has started,HPV typing remains necessary to monitor the changes in prevalence of the type(s) represented in the vaccines as a measure for vaccine ef?cacy.
HPV genotyping may also have some advantages and perhaps some prognostic value in monitoring of women who have been treated for CIN3or cervical cancer,although the treatment itself does not depend on the typing result.Demonstrating the same hrHPV type in the post-treatment specimen as in the primary CIN3lesion may indicate a recurrent hrHPV infection due to incomplete removal of the lesion or disability of the respective woman to clear a particular hrHPV type[16,17]and might require more intense follow-up or more aggressive treatment.
Finally,the number of known HPV types is still in-creasing.Although novel HPV types are often isolated from malignancies,their oncogenic potential can only be deduced from a combination of in vitro and epi-demiological studies,the latter of which should include typing.1.3.HrHPV types and risk of high-grade cervical
lesions
We showed that in the Dutch screened popula-tion[18],HPV types16and33are more preva-lent in women with a cytological reading of moderate dyskaryosis or worse and underlying CIN2or worse, than in women with normal cytology.This suggests that infection with these types confers an increased risk for development of high-grade cervical lesions[19]. Moreover,HPV type distribution in women with cer-vical carcinoma as compared with cytologically nor-mal women showed that HPV18is mainly a risk factor for the development of adenocarcinoma(AdCa)and its precursor adenocarcinoma in situ(ACIS),whereas HPV16is associated with both squamous cell carcino-ma(SCC)and AdCa[20].In line with the abovemen-tioned?ndings,an increased risk posed by HPV16and HPV18for cervical(pre)cancers of the squamous and adeno-histotypes was shown in a prospective screen-ing cohort of20810women followed for up to10 years[21].In addition,an increased risk for cervi-cal precancer posed by HPV16but not by HPV18was shown in a prospective trial of women with equivocal or mild cervical abnormalities[22].A likely expla-nation for increased prevalence of HPV18in invasive carcinoma but not in high-grade precursor lesions,is an association of HPV18with a cytopathological effect high in the endocervical canal that is likely to be missed by cytology.
These?ndings strongly suggest that in particular women who are HPV16or HPV18positive should be monitored very closely,even if their smears are cyto-logically normal.
2.HPV detection methods
Because HPV cannot be cultured,all HPV tests cur-rently in use rely on the detection of viral nucleic acids.HPV detection methods can be divided in target-ampli?cation methods and signal-ampli?cation meth-ods.In the following section,technical aspects of the different currently available HPV detection methods are described.
2.1.Target ampli?cation techniques
2.1.1.Consensus primer polymerase chain reaction
(PCR)
In most of the PCR-based HPV detection systems,a broad spectrum of HPV types is ampli?ed by consen-
A.A.T.P.Brink et al./HPV detection methods275
sus primers,followed by detection with type-speci?c probes.The consensus primers may be degenerate as in the MY09/11[23]and CPI/II[24]systems.Al-ternatively,they may contain mismatches that are ac-cepted under low-stringency PCR conditions as in the GP5+/6+system[25],they may contain inosine residues at ambiguous base positions such as in the IU/IWDO[26]and SPF[27]primers,or sets of over-lapping primers as is the case in the PGMY[28]and Amplicor[29]systems.
2.1.2.Detection and/or genotyping of consensus PCR
products
For group-speci?c detection of HPVs without high-resolution typing,an enzyme immuno assay(EIA)can be applied conveniently using cocktails of e.g.HR-or LR-HPV probes[30,31].
Typing of PCR products was traditionally done by means of dot blotting or Southern blotting and hy-bridization with type-speci?c oligonucleotides.More recently,reverse hybridization techniques were intro-duced.These methods rely on the hybridization of la-belled consensus PCR products to HPV-type speci?c oligos immobilized on?lters.Examples are reverse line blot(RLB)analysis following MY09/11[23]or GP5+/6+[25]consensus PCR,or a line probe assay (LiPa)following SPF PCR[27].Detection of the hy-bridized PCR product is done by a colorimetric reac-tion[23,27]or by chemiluminescence[25],the latter al-lowing repeated usage of the same?lter[25].Instead of ?lters,glass microarrays of HPV type-speci?c probes can also be used[32].Recently,a quantitative and high-throughput method was developed[33]based on Luminex suspension array technology.This method re-lies on detection of consensus primer PCR(GP5+/6+) products with type-speci?c oligonucleotide probes cou-pled to?uorescence-labelled polystyrene beads and al-lows detection of up to100different HPV types simul-taneously.
Two non-hybridization typing methods following consensus PCR are sequence analysis of the PCR prod-uct[34,35]and restriction fragment length polymor-phism(RFLP)analysis[36].RFLP implies the diges-tion of consensus PCR products with restriction en-donucleases,and comparison of the digestion pattern with those of known HPV types.These techniques are useful if unknown types of HPV are present in the spec-imens,but they have several drawbacks as compared with hybridization methods.For example,RFLP and sequence analysis are not suitable for the detection of infections with multiple HPV types:these will usually give an uninterpretable mix-up of digestion/sequence patterns.In addition,these two methods are less suit-able for high-throughput analyses because they are rel-atively laborious.Finally,RFLP and sequence analysis are less sensitive than hybridization methods because more PCR product is needed to generate a positive sig-nal.
As opposed to typing after consensus PCR,it is also possible to type during the reaction,in real time.Var-ious real-time PCR techniques are available(see also Section3.2.2),the best known being molecular bea-cons,the?uorescent5’exonuclease assay(e.g.Taq-man)and?uorescence energy resonance transfer assays (e.g.LightCycler).
At present the only real-time assay that allows con-sensus HPV-PCR with simultaneous typing is a molec-ular beacons assay[37].However,the multiplicity of this technique is limited because the current genera-tion of real-time thermocyclers do not allow for more than six differentially labelled probes.Hence,for typ-ing of multiple HPV infections,reverse hybridization methods are preferred over real-time assays.
2.1.
3.Type-speci?c PCR
If one is interested in a particular HPV type,type-speci?c PCR can be applied(described in[25,38] among others).Care should be taken when designing primers,because they may still react with other types if chosen in well-conserved regions.Con?rmation of the speci?city of type-speci?c PCRs,as with consensus primer PCRs,can be done by(regular or reverse)?lter hybridization or by EIA,but also in real-time[39–41].
A great advantage of real-time PCR assays is the pos-sibility to quantify the HPV in the specimen.Several studies have shown that the amount of hrHPV present in a cervical smear(the“viral load”)as measured by real-time PCR is predictive for the presence or develop-ment of high-grade cervical lesions[42–45];reviewed in[46].However,to obtain reliable quanti?cation data DNA extraction is usually necessary,thus increasing the work load.
2.1.4.mRNA ampli?cation
Several recent studies have shown that hrHPV test-ing can also be done through detection of the viral mR-NA.The most relevant transcripts to look for are those encoding the viral oncoproteins E6and E7.It is hy-pothesized that the presence of viral E6/E7mRNA in a cervical smear has a better positive predictive value for high-grade cervical lesions than the presence of viral DNA,because the E6/E7mRNA represents an active
276 A.A.T.P.Brink et al./HPV detection methods
infection with cell-transforming potential whereas the viral DNA may also be present in clinically irrelevant conditions.
Detection of viral mRNA in cervical smears can be done by reverse-transcriptase(RT-)PCR[47]or by nu-cleic acid sequence-based ampli?cation(NASBA)[48]. For the latter assay type,a commercially available sys-tem was recently developed that detects E6/E7tran-
screening and triage of women with smears showing minor cellular abnormalities.
An alternative method relying on hrHPV transcrip-tion is the detection of HPV-human fusion transcripts that arise from hrHPV genomes integrated into the host cell genome.This method was designated“am-pli?cation of papillomavirus oncogene transcripts”(APOT)[54].
Although this method is rather laborious and there-fore not suitable for large-scale hrHPV testing,it can give information that is not obtained using other mR-NA ampli?cation techniques.On the one hand,it re-veals viral integration,an event that is speci?c for a real precancerous lesion as opposed to a productive viral infection[55].On the other hand,it allows the iden-ti?cation of patient-speci?c fusion transcripts.This may be useful in monitoring of women who have been treated for high-grade lesions,because it will help to determine whether a high-grade lesion occurring after treatment is a recurrence or even a metastasis of the original lesion[56].
2.2.Signal-ampli?cation techniques
2.2.1.Liquid-phase signal ampli?cation techniques The best known technique in this category is the commercially available,FDA-approved and clinically validated Hybrid Capture2(HC2)method[57].This method uses a mixture of full-length RNA probes repre-senting hrHPV types16,18,31,33,35,39,45,51,52, 56,58,59,and68.Prior to the test,the clinical samples are heat-alkaline-denatured.Hybridization of one or more of the probes to HPV DNA present in the samples is detected by peroxidase-labelled antibodies that rec-ognize the RNA/DNA hybrid,and visualized by chemi-luminescence.The analytical sensitivity of this method is1pg/ml of cloned HPV16DNA,which corresponds to approximately105HPV16genome copies.This sen-sitivity is lower than that of most target-ampli?cation methods.Because a mixture of probes is used,HC2is at present not suitable for high-resolution typing.Some cross reactivity of the HC2probes with HPV types not represented in the probe mix,including non-oncogenic HPVs,has been described[58].
2.2.2.Morphological signal-ampli?cation techniques In addition to the abovementioned methods,hrH-PV detection can be performed by DNA in situ hy-bridization(ISH)to cytological slides[59,60]and his-tological preparations[61].This can be achieved by ?uorescent detection[61]or colored substrate deposi-tion and bright?eld microscopy.The relatively small size of the HPV genome(7.8kb)and thus of the probe precludes direct detection of hybrids in case of low viral genome copy numbers and therefore some type of signal ampli?cation is generally necessary.A commercially available HPV ISH system uses an indi-rect biotin-streptavidin method(Ventana Inform HPV) which at present lacks suf?cient sensitivity to detect high-grade cervical lesions[60].Alternatively,tyra-mide signal ampli?cation(TSA),also known as catal-ysed reporter deposition(CARD)can be used,both in ?uorescent[61,62]and bright?eld[62]applications. Also for the CARD method,a commercially available system exists(Dako GenPoint).CARD greatly en-hances sensitivity,but in general HPV ISH is too labo-rious to be used in high-throughput HPV testing.
3.Clinical specimens for HPV detection
The kind of clinical specimens available will deter-mine the choice of the HPV detection method.Most PCR methods mentioned above can be done with any type of clinical material,including formalin-?xed, paraf?n-embedded tissue and Pap-stained archival smears.The recent focus on liquid-based cytology (LBC)for cervical cancer screening has initiated nu-merous studies evaluating the feasibility of different HPV detection methods on cell suspensions destined for LBC,or cell suspensions remaining after LBC preparation.Some of the pros and cons of different types of clinical specimens are discussed below.
A.A.T.P.Brink et al./HPV detection methods277
3.1.Clinical specimen types suitable for target
ampli?cation methods
3.1.1.Specimen types for PCR-based methods
PCR-based HPV DNA detection methods can gen-erally be applied to all kinds of clinical specimens, provided the nucleic acids contained within are not heavily degraded or cross-linked and no putative PCR-inhibiting substances(https://www.doczj.com/doc/322767038.html,anic solvents)are present.Notably,the nucleic acids in formalin-?xed, paraf?n-embedded(FFPE)tissue are only ampli?ed in a reliable manner when PCR products are generated that are smaller than150bp due to?xative-induced cross links[63].On the other hand,this type of speci-men generally does not contain large amounts of PCR-inhibiting substances,as demonstrated by the fact that a relatively crude extract can be used in the PCR without laborious extraction protocols[64].
As opposed to FFPE material,cervical smears col-lected in LBC media may show excellent preservation of cell morphologyand integrity of nucleic acids.How-ever,to achieve this preservation they usually contain relatively high amounts of organic solvents which will inhibit the PCR and need to be removed by careful ex-traction.An exception are smears collected in Digene Universal Collection Medium(UCM)[65,66],which can be used directly in the PCR after a simple dilution and freeze-thaw protocol(Hesselink et al.,submitted). Pap-stained archival cervical smears can also be used for PCR purposes,but they also need extraction of nu-cleic acids to remove remnants of dyes.In addition, the nucleic acids in this type of specimen may also be degraded due to?xation artefacts.For all above-mentioned samples,careful analysis of the nucleic acid quality is recommended to exclude false negative HPV test results due to DNA degradation and/or PCR inhi-bition.This can be achieved e.g.by a PCR speci?c for a human single-copy gene[67].
For most reliable PCR results,it is recommended to standardize the amount of input DNA in the PCR.It is self-evident that this can only be done using puri?ed nucleic acids.
3.1.2.Specimen types for mRNA ampli?cation
methods
Until recently,hrHPV mRNA testing on cervical smears was hampered by the lack of suitable collection media.The poor RNA quality of samples collected in solutions such as
PBS precluded transcription anal-ysis.However,use of LBC is increasing and this is accompanied by the introduction of preservation media PreservCyt LBC medium are of suf?cient quality for HPV RT-PCR[68]and NASBA analysis[69]. Alternatively,cervical smears could be collected in a dedicated RNA-preservation buffer[51],but in gen-eral these contain chaotropic salts such as guanidinium isothiocyanate and thus destroy cellular morphology. When hrHPV mRNA is to be detected in cervical biopsy specimens,these should preferably be snap-frozen to guarantee mRNA integrity.However,several groups claim successful mRNA extraction from FFPE material(reviewed in[70]).Provided the use of proper quality controls,this is of course a very interesting source of material,especially for retrospective studies or in situations where snap-freezing is not an option.
3.2.Clinical specimen types suitable for
signal-ampli?cation methods
The Digene HC2method is FDA-approved for use on cervical smears and cervical biopsies collected in Digene’s Sample Transport Medium(STM).In addi-tion,the FDA-approval of HC2includes use on cer-vical smears collected in Cytyc’s ThinPrep medium. However,because this medium preserves cell integrity as opposed to STM,ThinPrep smears require an addi-tional pre-treatment to obtain full cell lysis and release of nucleic acids[71].With some modi?cations of the standard protocol,HC2can also be used on the residual material of cervical smears collected in SurePath?uid (i.e.the suspension that remains after the LBC slides have been prepared)[72–74].
An intermediate between the commercially available LBC media that preserve cell morphology but require pre-treatment steps prior to HC2,and Digene’s STM that does not require pre-treatment but destroys cell morphology,is Digene Universal Collection Medium (UCM).This medium can be used for sample trans-port[66],does not require additional steps prior to HC2 analysis,and because it preserves cell morphology it also allows LBC[65].
4.Considerations regarding test sensitivity and
speci?city
4.1.Considerations for primary screening and triage In general,the analytical sensitivities of HPV tests depend on the test system(target ampli?cation ver-
278 A.A.T.P.Brink et al./HPV detection methods
sus signal ampli?cation).The sensitivity of the HC2 method is approximately5,000copies of the HPV genome per reaction well according to the manufac-turer.PCR-based techniques have a much higher ana-lytical sensitivity than HC2,with a slight variation be-tween the methods(reviewed in[46]).For most PCR assays,less than100to1000HPV genome equivalents in a reaction tube are suf?cient to generate a positive PCR signal and to enable typing.
Despite these high analytical sensitivities,currently available hrHPV tests miss a subset of high-grade CIN lesions[75,76].This may be due to several factors. For PCR-based methods,modi?cation or loss of primer binding sites due to viral integration or naturally oc-curring sequence variants may be a problem.For HC2 where whole-genome probes are used this is generally not an issue,but then the lower analytical sensitivity of HC2might preclude detection of lesions with low viral loads.The ideal hrHPV test used in primary screen-ing should combine the high analytical sensitivity of PCR assays with the possibility to detect all con?gu-rations and variations of the hrHPV genome,including integrated genomes.Because the intact E6/E7region of the hrHPV genome is necessary for cellular trans-formation[77]and is invariably retained upon integra-tion[78],a PCR system detecting this region would be the method of choice[79].It is self-evident that ampli-?cation primers should then be chosen in such a way that they cover all known HPV genomic variations. On the other hand,a very sensitive hrHPV test con-sequently has a low clinical speci?city,and as a pri-mary screening tool it would result in a substantial in-crease in referrals for colposcopy and repeat smears.In the Dutch screening population,approximately5.0%of the women is hrHPV DNA-positive by the GP5+/6+ system[18].Because even women with hrHPV DNA-positive normal cytology have a210times greater risk to develop CIN3compared to women with hrHPV negative normal cytology[80],all5.0%hrHPV DNA-positive women would need follow-up.However,only 10%of them will actually develop CIN3[81].This calls for additional strati?cation of women who have a positive hrHPV DNA test,which can be achieved for example by viral load analysis or HPV mRNA analysis (see Sections2.1.3and2.1.4).
4.2.Considerations for situations not involving triage For several research questions,clinical speci?city of the hrHPV test is not an issue as it is in population-based screening and triage.Methods with high analytical sensitivity are especially suitable for studies in which any HPV infection should be detected,irrespective of its clinical relevance.Examples are epidemiological studies,and studies to determine vaccination ef?cacy. It is self-evident that HPV genotyping is desired in such studies.
5.Conclusions
As seen in the previous paragraphs,the aim of the study and the clinical material available will determine the choice of the HPV detection method.In general, consensus PCR followed by reverse hybridization is very sensitive and gives the most extensive typing infor-mation for many kinds of clinical specimens,including those containing multiple infections.
In general,it is to be expected that future ampli?ca-tion systems will become faster and more automated. References
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最佳答案 汽车制造业中的 HPV 即单车工时 含义—— 体现生产一台车实际投入了多少人时或者多少工作时间 HPV作用： 一、对于一个汽车制造商来说，单车工时（HPV)是企业整体竞争力的衡量指标。 单车工时（生产率）的情况反应了工程设计、制造执行和其他工人的执行效率。 1、如果单车工时（HPV)下降，则表明实际生产一台车投入人时减少，成本降低； 2、如果单车工时（HPV)上升，则表明实际生产一台车投入人时增加，成本加大。 3、体现实际生产时的效率，不能体现全员的数量，淡季的时候，产量小，员工轮休，配相应少的人员上班，只能体现上班人员的效率，单车工时（HPV)保持，但富余（轮休）人员的效率情况体现不了。 二、原则 1、原则上以车型为单位计算每款车型的单车工时情况，工艺分为焊装、 涂装、总装； 2、由于大部分是混型柔性生产线，按车型实际投入人时计算不易划分， 则混线各车型都使用该生产线人时计算 三、计算方式 整车单车工时（整车HPV)=∑一个月工厂总人员总工作时间/ ∑整车产量 车间： 焊装单车工时（焊装HPV)=∑一个月焊装车间人员总工作时间/ ∑焊装产量 涂装单车工时（焊装HPV)=∑一个月涂装车间人员总工作时间/ ∑涂装产量
总装单车工时（焊装HPV)=∑一个月总装车间人员总工作时间/ ∑整车产量 四、单车工时(HPV)影响因素 1、产量影响——班次、节拍： 由于产量的波动对班次和节拍产生了影响，导致HPV发生变化。 产量减少时： 1）由于工厂非一线人员不能按产量减少量同比减少，导致HPV增大； 2）节拍减少时，由于一线人员不能及时按产量减少量同比减少和对应， 导致HPV增大： 备注：因产量减少，轮休人员虽不影响HPV，但这部分人的效率体现不出来。 2、时间影响——稼动率： 计划停线：新品停线、参观停线、排空布线影响、生产管理部安排的计划、吃饭停线 计划固有停线：5S、交接班、点检、清洗自动机等 异常停线：设备、人员、技术质量（含产品设计类）、能源供应、其他（含物料影响）五个类别； 由于停线导致产量减少，人时不变，最终导致HPV增大； 3、人员影响——一线、辅助、业务人员数量： 一线人员： 1）由于一线人员节拍平衡影响或其他工艺影响，导致生产线人员 较多，导致生产线人时增加，HPV增大： 2）由于一线人员作业技能影响，导致生产线人员较多，导致生产线人时 增加，HPV增大： 辅助、业务人员数量影响
HPV常见问题 什么是HPV？ 回答：人乳头瘤病毒（Human Papilloma Virus，HPV），是一种常见的感染皮肤和黏膜组织的病毒，大约有100多种HPV型别。引起普通疣的HPV型别主要通过皮肤接触传染，常发生在手、足部位。与这类患者共用毛巾或其他物品也会感染这一类型的HPV。与生殖道相关的HPV大约有30种型别，主要分为两大类。一是高危型HPV ——即持续感染会引起某类癌症（最常见的是宫颈癌）；另一是低危型HPV ——不会引起癌变，但常引起生殖道疣。无论感染哪一种型别的HPV，唯一可以确定您是否携带HPV病毒的方法是进行检测。HPV感染有多常见？ 回答：和感冒一样，HPV感染也非常普遍。大约80%的女性一生都会感染HPV，但是，大部分的感染在一两年内可自动消除或被自身免疫力抑制，不会引起任何病变，无需治疗。 HPV的传播途径 回答：和生殖道相关的HPV型别，主要通过xing行为或皮肤的亲密接触传播，空气、日常生活的简单接触，诸如握手是不能传播的。避孕套有一定的保护作用，但由于它不能覆盖全部的生殖器，因此不能完全防止感染。多个xing伴侣会提高感染HPV的风险，但即便只有一个xing伴侣，女性也应当定期进行宫颈癌的筛查。这是因为，HPV可能在宫颈细胞中潜伏几个月甚至几年。在潜伏期间，病毒没有活性，无法检测到，不会传播，也不会致bing。然而，当机体免疫力下降时，此类感染可能会再次复活并引起细胞发生异常改变。目前还无法明确检测出，究竟是何时、何地、从谁那里感染到的HPV。 HPV会通过kou交传播吗？ 回答：这个问题还在研究中。某些研究发现25-35%的口腔癌与高危型HPV相关。然而按照普遍存在的口交行为，美国妇产科专家认为通过这个途径传播HPV的可能性是非常小的。 男性也会感染HPV吗？ 回答：会。和女性一样，男性感染HPV也不会有任何症状。尽管HPV感染在男性可能会引发阴jing癌或肛门癌，但非常少见。另外，没有可靠的方法，从男性生殖道皮肤采集样本用于HPV检测。目前还没有任何美国FDA许可的男性HPV检测方法。
人类乳突病毒（Human Papillomavirus，简称HPV）是一种嗜上皮性病毒，有高度的特异性，长期以来，已知HPV可引起人类良性的肿瘤和疣，如生长在生殖器官附近皮肤和粘膜上的人类寻常疣、尖锐湿疣以及生长在粘膜上的乳头状瘤。像乙肝病毒一样，HPV也是一种DNA病毒。它原是多瘤空泡病毒科的一员，1999年国际病毒分类委员会（ICTV）取消多瘤空泡病毒科，代之以乳头瘤病毒科，因此，HPV便归属此门下。 基本组成 HPV是一种具有种属特异性的嗜上皮病毒，属双链闭环的小DNA病毒，包含约8000个碱基对 人乳头瘤病毒(HPV)结构图 。其中包括8个早期开放读码框架（E1-E8）、2个晚期读码框架和1个非编码长控区。在早期开放读码框架中，E6和E7基因对细胞生长刺激最为重要，E6、E7编码的E6、E7蛋白引起宫颈上皮细胞永生化。而晚期读码框L1和L2基因分别编码HPV的主要和次要衣壳蛋白，组装成HPV的衣壳。将HPV“解剖”开来会发现，它由蛋白衣壳这层外衣和被包裹着的核心构成。衣壳的“原料”主要是衣壳蛋白（L1）和次要衣壳蛋白（L2）；褪掉衣壳，其核心是能引起人类疾病的真身——无包膜呈现小型双链环状的DNA。1949年，Strauss首先在电镜下观察到HPV颗粒，它呈球形，其20面体对称，直径约45-55nm。根据HPV 基因序列结构的不同，人们将HPV分为近130种基因型，其中近百种的基因序列已被摸清。人类是HPV的唯一宿主，它最喜欢把家安在皮肤和黏膜内，因此具有高度的宿主特异亲和力。[1] 传播途径 HPV是一种性传播微生物。它能通过皮肤或黏膜的微小损伤，进入接触者的皮肤黏膜，HPV刺激表皮基底细胞，产生分裂，使表皮产生增殖性损害。在1954年，HPV便被证实是性传播疾病的病原之一，与泌尿生殖系尖锐湿疣有关，并具有传染性。此外，HPV 还可通过母亲与婴儿间的亲密接触，而发生病毒的母婴传播。生活中，极少数的病例还可能因接触带有HPV的生活用品而感染，如内裤、浴盆或浴巾。医学研究表明，诸多因素可影响HPV的感染。比如，30岁以后的妇女HPV感染率低。丈夫阴茎若有HPV，可使妻子宫颈感染HPV的危险增加9倍。甚至男性性伴侣的数量，也与妇女HPV的感染相关。在
Home ? 2015 Issues, May 2015, Past Articles Negative Pap, positive hrHPV: what we know so far Rebecca Ocque, MD Chengquan Zhao, MD May 2015—Cervical cancer is the second most common cancer in women worldwide, and high-risk human papillomavirus (hrHPV) is considered the principal causative factor in the development of most cervical cancer and its precursor lesions. For this reason, screening algorithms that include testing for hrHPV are part of the new cervical cancer screening guidelines set forth by the American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for Clinical Pathology. Within the new guidelines, women age 30 and older can be screened with cytology alone and rescreened in three years if they have a negative result, or screened alternatively with both cytology and hrHPV testing every five years if both tests are negative.1 More than 150 HPV types have been fully characterized, with about 40 being transmitted through sexual contact and infecting the anogenital region. HPV types have been referred to as low risk or high risk, based on their associated risk for cervical cancer. Low-risk HPV (lrHPV) types (6, 11, 42, 43, 44, 54, 61, 62, 70, 72, 81) are virtually never found in cervical cancers, while hrHPV types (16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, 73, 82) have been identified in cancers of the cervix, vagina, vulva, anus, and penis. Currently there are five Food and Drug Administration-approved hrHPV tests for clinical samples. Digene Hybrid Capture 2 High-Risk HPV DNA Test was the first approved test that identifies 13 hrHPV types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68). The Cervista HPV HR and Genfind DNA Extraction Kit identifies DNA from 14 high-risk HPV types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68). Positive tests can then have reflex subtyping performed with Cervista HPV 16/18. The Cobas HPV Test, made by Roche, specifically identifies types HPV 16 and HPV 18 while concurrently detecting 12 other hrHPV types (31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68). In 2014, the FDA approved the Cobas HPV Test as the first cervical cancer screening test to be used alone without cervical Pap cytology for women age 25 and older. The most recent test to enter the U.S. market, Aptima HPV Assay, identifies HPV RNA from viral oncogenes E6 and E7 from 14 hrHPV types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68).
关于HPV的一些认识 人乳头瘤病毒（HPV）是一种属于乳多空病毒科的乳头瘤空泡病毒A属，是球形DNA病毒，能引起人体皮肤黏膜的鳞状上皮增殖.目前已分离出130多种，不同的型别引起不同的临床表现，根据侵犯的组织部位不同可分为: （1）皮肤低危型：包括HPV1、2、3、4、7、10、12、15等与寻常疣、扁平疣、跖疣等相关； （2）皮肤高危型：包括HPV5,8，14，,17,20,36,38与疣状表皮发育不良有关，其他还与可能HPV感染有关的恶性肿瘤包括：外阴癌、阴茎癌、肛门癌、前列腺癌、膀胱癌； （3）黏膜低危型如HPV-6，11，13，32，34，40，42，43，44，53，54等与感染生殖器、肛门、口咽部、食道黏膜； （4）黏膜高危型HPV-16、18、30、31、33、35、39与宫颈癌、直肠癌、口腔癌、扁桃体癌等。 生物学活性：HPV抵抗力强，能耐受干燥并长期保存，加热或经福尔马林处理可灭活，所以高温消毒和2%戊二醛消毒可灭活。[1-2] [3] 流行病学 皮肤型的HPV人群感染率非常普遍，如上述常见的寻常疣、趾疣、扁平疣等，无法得到具体的感染率，比较引起注意到是高危型的HPV感染和外生殖器的低危型HPV感染造成的生殖器疣和宫颈癌，据统计在全球的性病中，HPV感染引起的生殖器疣占15-20%。 关于女性生殖道感染HPV的流行情况，据2003-2004年来自美国的国家健康和营养研究课题的一个调查结果显示，14-59岁的HPV总感染率为26.8%,所以HPV感染在女性造成的负担超出之前的估计。我国的HPV 感染的流行病学筛查未见大样本的报告，但是由HPV感染造成的性病中的尖锐湿疣的发病率在迅速上升，估计发病率应该是性病中最多的，因为存在大量的漏报和不报。我国每年约有13.15万新发现的宫颈癌,报告中发病率和死亡率有增加趋势，且宫颈癌发病年龄年轻化，可以预见Hpv感染造成在我国造成的损失的巨大.[2] [3] [5] 感染途径 1、性传播途径； 2、密切接触； 3、间接接触：通过接触感染者的衣物、生活用品、用具等； 4、医源性感染：医务人员在治疗护理时防护不好，造成自身感染或通过医务人员传给患者； 5、母婴传播：是由婴儿通过孕妇产道的密切接触。[2] 临床表现 低危型HPV感染 1、良性皮肤表现 （1）寻常疣：米粒大小的丘疹，表面角化明显，粗糙不平、顶端刺状，质地坚硬，皮损可单个，也可多个，可自身接种而逐渐增多。多发生在手、足等 （2）特殊部位表现疾病： 甲周疣：发生在指、趾甲周围，表现为甲下增厚、角化。 跖疣：发生在足跖部位，皮损表面因受压可见出血点和黑点。 丝状疣：发生在颈部、眼睑的呈柔软丝状多个细小疣 扁平疣：多发生在面部，躯干部位也常见，多为2-5mm大小的扁平丘疹，肤色或淡褐色，表面光滑，圆形或类圆形，偶因瘙痒而搔抓形成自身接种，或沿皮肤损伤表面种植。 2、外生殖器疾病良性表现 （1）生殖器疣（尖锐湿疣）：包括三种状态：典型表现、亚临床感染、潜伏感染。
HPV:人乳头状瘤病毒。60％～70％的女性感染过hpv 病毒感染 一直以来，人们尤其是女性，对于子宫颈癌心里存在着相当大的恐惧。其实，子宫颈癌并不可怕，它是目前所有癌症当中，唯一可以能有效预防、早期及时发现、并且能早期治疗的癌症。对宫颈癌存有恐惧感的女性，多数是源于对宫颈癌相关知识方面的认识不足。 现代医学通过研究已经确认，女性患宫颈癌是子宫颈被人乳头状瘤病毒（HPV）感染所致。虽然宫颈癌和HPV之间存在着相关联系，但不是所有感染了HPV的女性都会患宫颈癌。 由于HPV广泛存在于自然界，人的皮肤、消化道、呼吸道等都携带有这种病毒。所以，凡是有性生活的女性，都有可能通过性接触，将HPV带到自己的生殖道内。医学工作者曾对18～28岁的女性进行过普查，发现HPV感染者并非少见。专家推测：就女性而言，hpv的终身感染率累积可高达60％～70％。也就是说，60％～70％的女性，在其一生中都感染过HPV，但这种感染通常是一过性的。 因为当人体感染了这种病毒以后，机体内会逐渐，少数患者会很快形成对该病毒的免疫力，当免疫能力足够强大时，HPV就会被清除。所以大量医学统计资料表明，虽然被HPV感染的人群比例很大，但大多为一过性，即在1年－2年时间病毒就会自然消失（泛指HPV感染）。大多数女性体内的免疫系统可以把进入体内的HPV消灭掉，只有少数免疫机能比较弱的女性，无法消灭进入体内的HPV，造成HPV持续感染，但这个过程大约需要8～12年时间，才可能发展成为子宫颈癌。 临床上发现的子宫颈癌患者，差不多都是30岁以上的妇女。所以，有性生活的女性可以在30岁以后开始进行HPV-DNA检查。检查结果为阴性的，说明没有被HPV感染，因而在很长一段时间内都不会有患子宫颈癌的危险。因此，可以隔3年再作此项检查。检查结果为阳性的，也不一定就会发展成子宫颈癌，因为体内的免疫系统有可能将病毒消灭掉。只是有发展成子宫颈癌的可能，所以，首先应该再作一个子宫颈涂片检查，看目前有没有已经异常的子宫颈细胞。如果没有，应每年复查这两项检查。一旦发现异常马上进行治疗，这样就可以将子宫颈癌消灭在萌芽状态。 因此，就女性而言，hpv的感染具有较强的广泛性和自限性。即使感染了HPV也没有什么可害怕的，通常人体自身都能够将其逐步清除，免疫力稍查的
综述 抗HPV治疗：现况&展望 在认识HPV为宫颈癌的病因至今已有25年，仍缺乏对HPV感染的有效治疗。仅仅在最近几年开始特异性的针对HPV感染的靶向综合治疗。对于HPV诱导的病变传统的物理消融术如冷冻治疗，光疗，LEEP，激光锥切和局部放疗，通过切除与含有HPV的转化角化细胞相连的病变组织从而对局部病变有一定的疗效。除了目前可获得的预防性疫苗可在暴露于病毒感染前接种从而阻止病毒入侵，现在开始研究治疗性的疫苗来治疗HPV感染。此外，免疫调节剂如干扰素和咪喹莫特被证实能诱发细胞因子来增强宿主对HPV感染的免疫。另外，抗病毒方法如RNA干扰核苷酸类似物，抗氧化剂和中草药衍生物被证实具有抗HPV感染的治疗潜能。这些在临床前和临床研究中都得到测试。非切除的抗HPV治疗手段不仅对于早期HPV病毒尚未整合入宿主细胞基因组具有清除HPV的作用，而且对于在转化之后HPV致癌基因异常调节宿主细胞周期的阶段，对于病毒致癌基因表达具有抑制作用。 导言 HPV基因型的多样性与其引起上皮增生病变的广谱性能力有关。与HPV 感染相关的疾病在全球疾病中所占比例非常高，估计在所有癌症中大约有5.17%与HPV感染有关。在HPV感染相关疾病中，宫颈癌作为世界女性第二常见癌症占首位。乳头瘤病毒对不同器官部位的鳞状上皮细胞展现出高的细
胞向性运动并与不同的临床疾病相关如良性的上皮增生性病变如疣，乳头瘤或浸润性癌症相关。基于所致疾病类型，乳头瘤病毒被分为高危型(HR)和低危(LR)型。HR-HPV(HPV16,18,31，39, 45, 51, 52, 56, 59, 66, 68, 69和73)通常与高级别病变和浸润性癌症相关，LR-HPV((HPV 6, 11, 40, 42, 43, 44, 54, 61, 70, 72, 81, CP6108)常见于低级别病变，生殖器或皮肤疣和尖锐湿疣。目前大约有15种高危型HPV被认为对HPV导致的癌症有100%的作用。其中HPV16和18是最普遍的致癌基因型，二者在HPV相关的癌症病变中占据80%。 特定的高危型HPV持续性感染尤其是16型和18型是CIN和宫颈癌发展的前提。尽管如此，HPV感染是一个短暂的现象。在感染之后，病毒可能持续一段时间，在病毒以非整合形式存在时导致低度宫颈病变发展，而发展为宫颈癌需要15—20年。尽管HPV感染的自然历程表现出很大比例的自发性清除，高危型HPV感染持续一年或更久标志着进展为癌症的风险增高。目前发现清除特定类型HPV感染需要大约2年的时间。尽管HPV基因型，一个8kb的环形DNA，编码大约6个早期基因（E1, E2, E4, E5,E6 和E7) 和两个晚期基因(L1 和L2)。HR-HPV的E6和E7在体外试验中能使人类鳞状上皮细胞永生化，这一发现建立了病毒在宫颈癌中的作用，病毒编码的E6和E7致癌蛋白与重要的细胞周期调节蛋白相互作用。生殖器部位的HPV的E7蛋白，同于腺病毒的E1A蛋白和多瘤病毒的大肿瘤抗原，能与视网膜母细胞瘤肿瘤抑制基因（pRB）形成复合体进而干扰pRB与E2F转录因子的结合,高危型HPV的E7蛋白如HPV16和18相比低危型HPV6型和11型的E7蛋白，与pRB结合的
HPV常见问题 什么是HPV 回答：人乳头瘤病毒（Human Papilloma Virus，HPV），是一种常见的感染皮肤和黏膜组织的病毒，大约有100多种HPV型别。引起普通疣的HPV型别主要通过皮肤接触传染，常发生在手、足部位。与这类患者共用毛巾或其他物品也会感染这一类型的HPV。与生殖道相关的HPV大约有30种型别，主要分为两大类。一是高危型HPV ——即持续感染会引起某类癌症（最常见的是宫颈癌）；另一是低危型HPV ——不会引起癌变，但常引起生殖道疣。无论感染哪一种型别的HPV，唯一可以确定您是否携带HPV病毒的方法是进行检测。 HPV感染有多常见 回答：和感冒一样，HPV感染也非常普遍。大约80%的女性一生都会感染HPV，但是，大部分的感染在一两年内可自动消除或被自身免疫力抑制，不会引起任何病变，无需治疗。 HPV的传播途径 回答：和生殖道相关的HPV型别，主要通过xing行为或皮肤的亲密接触传播，空气、日常生活的简单接触，诸如握手是不能传播的。避孕套有一定的保护作用，但由于它不能覆盖全部的生殖器，因此不能完全防止感染。多个xing伴侣会提高感染HPV的风险，但即便只有一个xing伴侣，女性也应当定期进行宫颈癌的筛查。这是因为，HPV可能在宫颈细胞中潜伏几个月甚至几年。在潜伏期间，病毒没有活性，无法检测到，不会传播，也不会致bing。然而，当机体免疫力下降时，此类感染可能会再次复活并引起细胞发生异常改变。目前还无法明确检测出，究竟是何时、何地、从谁那里感染到的HPV。 HPV会通过kou交传播吗 回答：这个问题还在研究中。某些研究发现25-35%的口腔癌与高危型HPV相关。然而按照普遍存在的口交行为，美国妇产科专家认为通过这个途径传播HPV的可能性是非常小的。 男性也会感染HPV吗 回答：会。和女性一样，男性感染HPV也不会有任何症状。尽管HPV感染在男性可能会引发阴jing癌或肛门癌，但非常少见。另外，没有可靠的方法，从男性生殖道皮肤采集样本用于HPV检测。目前还没有任何美国FDA许可的男性HPV检测方法。?
HPV病毒简介 湿疣是由人类乳头瘤病毒（HPV）感染引起的一种性传播疾病。主要类型为HPV1、2、6、11、16、18、31、33及35型等， HPV16和18型长期感染可能与女性宫颈癌的发生有关。 HPV病毒（人乳头瘤病毒缩写）是一种属于乳多空病毒科的乳头瘤空泡病毒A属，是球形DNA 病毒，能引起人体皮肤黏膜的鳞状上皮增殖.目前已分离出130多种，该病毒只侵犯人类，对其它动物无致病性，人体一旦感染会终生携带。 不同的型别引起不同的临床表现，根据侵犯的组织部位不同可分为： （1）皮肤低危型：包括HPV-1、2、3、4、7、10、12、15等与寻常疣、扁平疣、跖疣等相关； （2）皮肤高危型：包括HPV-5、8、14、17、20、36、38与疣状表皮发育不良有关，其他还与可能HPV感染有关的恶性肿瘤包括：外阴癌、阴茎癌、肛门癌、前列腺癌、膀胱癌；（3）黏膜低危型如HPV-6、11、13、32、34、40、42、43、44、53、54等与感染生殖器、肛门、口咽部、食道黏膜； （4）黏膜高危型HPV-16、18、30、31、33、35、39与宫颈癌、直肠癌、口腔癌、扁桃体癌等。 生物学活性：HPV抵抗力强，能耐受干燥并长期保存，加热或经福尔马林处理可灭活，所以高温消毒和2%戊二醛消毒可灭活。 HPV感染途径 1、性传播途径； 2、密切接触； 3、间接接触：通过接触感染者的衣物、生活用品、用具等； 4、医源性感染：医务人员在治疗护理时防护不好，造成自身感染或通过医务人员传给患者； 5、母婴传播：是由婴儿通过孕妇产道的密切接触。 低危型HPV感染 1、良性皮肤表现 （1）寻常疣：米粒大小的丘疹，表面角化明显，粗糙不平、顶端刺状，质地坚硬，皮损可单个，也可多个，可自身接种而逐渐增多。多发生在手足等。 （2）特殊部位表现疾病： 甲周疣：发生在指、趾甲周围，表现为甲下增厚、角化。
hpv是什么 60％～70％的女性感染过hpv 病毒感染 一直以来，人们尤其是女性，对于子宫颈癌心里存在着相当大的恐惧。其实，子宫颈癌并不可怕，它是目前所有癌症当中，唯一可以能有效预防、早期及时发现、并且能早期治疗的癌症。对宫颈癌存有恐惧感的女性，多数是源于对宫颈癌相关知识方面的认识不足。 现代医学通过研究已经确认，女性患宫颈癌是子宫颈被人乳头状瘤病毒（HPV）感染所致。虽然宫颈癌和HPV之间存在着相关联系，但不是所有感染了HPV的女性都会患宫颈癌。 由于HPV广泛存在于自然界，人的皮肤、消化道、呼吸道等都携带有这种病毒。所以，凡是有性生活的女性，都有可能通过性接触，将HPV带到自己的生殖道内。医学工作者曾对18～28岁的女性进行过普查，发现HPV感染者并非少见。专家推测：就女性而言，hpv的终身感染率累积可高达60％～70％。也就是说，60％～70％的女性，在其一生中都感染过HPV，但这种感染通常是一过性的。 因为当人体感染了这种病毒以后，机体内会逐渐，少数患者会很快形成对该病毒的免疫力，当免疫能力足够强大时，HPV就会被清除。所以大量医学统计资料表明，虽然被HPV
感染的人群比例很大，但大多为一过性，即在1年－2年时间病毒就会自然消失（泛指HPV感染）。大多数女性体内的免疫系统可以把进入体内的HPV消灭掉，只有少数免疫机能比较弱的女性，无法消灭进入体内的HPV，造成HPV持续感染，但这个过程大约需要8～12年时间，才可能发展成为子宫颈癌。 临床上发现的子宫颈癌患者，差不多都是30岁以上的妇女。所以，有性生活的女性可以在30岁以后开始进行HPV-DNA 检查。检查结果为阴性的，说明没有被HPV感染，因而在很长一段时间内都不会有患子宫颈癌的危险。因此，可以隔3年再作此项检查。检查结果为阳性的，也不一定就会发展成子宫颈癌，因为体内的免疫系统有可能将病毒消灭掉。只是有发展成子宫颈癌的可能，所以，首先应该再作一个子宫颈涂片检查，看目前有没有已经异常的子宫颈细胞。如果没有，应每年复查这两项检查。一旦发现异常马上进行治疗，这样就可以将子宫颈癌消灭在萌芽状态。 因此，就女性而言，hpv的感染具有较强的广泛性和自限性。即使感染了HPV也没有什么可害怕的，通常人体自身都能够将其逐步清除，免疫力稍查的女性只需要每年定期做妇检防癌筛查，就能够完全避免宫颈癌的发生。 人类乳头状瘤病毒（Human papillomavirus，HPV）是一种嗜上皮性病毒，有高度的特异性，长期以来，已知HPV可引
女性hpv有几种检查方法 当代社会女性的身体疾病越来越严重，种类也越来越多，女人总是先想着怎么照顾好家人以及孩子，却很少给自己做一个健康检查的计划。有时候为了家庭为了孩子就是身体有一点不舒服也没有放在心上，毕竟去趟医院就是就是一大笔的开销。今天小编就为您简单的说明一下女性疾病重的一种hpv那么女性hpv有几种检查方法呢？ 女性hpv有几种检查方法 首先要给您说明一下的是什么是hpv？hpv人乳头瘤病毒的简称。是一种属于乳多空病毒科的乳头瘤空泡病毒A属，是球形DNA病毒，能引起人体皮肤黏膜的鳞状上皮增殖。 第一种，原位杂交法（ISH）。这种方法可以检测出细胞内的hpv的DNA，可以准确定位感染病毒的细胞位置，特异性也很好，但是由于太准确了，每种类型的hpv都需要特定的探针和试剂，所以临床上并不能大面积开展使用，因为太贵了。 第二种，聚合酶链反应检测（PCR）中文可能并不熟悉，但是如果查过hpv病毒的人，检查单上估计也可以看见PCR的这三个字母，这是国内最常见，最广泛的一种检查。它的作用，就是通过检查hpv的DNA，来确定病毒的型号，也就是流传最广的hpv分型检测。但这种检测的方法缺点，就是不能检查病毒的量，只能查出分型。 第三种第二代杂交捕获实验检测（HC-2）这个也是很熟悉的了吧，在某些地区也是很盛行的，一来就HC-2的。但是这种检测法的缺点，就是只能检测高危组和低危组这2组一共含有的病毒数量，也就是说只有一个值，无法看出病毒的分型和具体哪种型号的载量多少。女性感染HPV就会得癌症吗 虽然当今社会好多宫颈癌患者都是因为感染了hpv，但是并不代表感染了hpv就一定会得癌症，只是高危hpv患者持续感染才会引发宫颈癌，一般多数人会被人体的免疫系统自动清除的。 每个人的身体机制都是不一样的，就连医生有时候也无法坚定的给出一个不变的答案，很多的时候我们不能一概而论。如今社会的科技在发展，我们高科技的产品越来越多，面对很多疾病也会游刃有余的。所以我们不必压力山大，给自己一点希望，世界会还你一个奇迹！
对于开展HPV16、18型检测的相关调查报告 一、文献引用： 目的：了解中国妇女不同子宫颈病变中人乳头瘤病毒（HPV）型别分布特点，估计HPVl6／18型预防性疫苗的应用前景。 方法：在18个用PCR方法检测子宫颈HPV型别分布的国内外研究中，共包括1335例浸润性子宫颈癌（ICC）、394例子宫颈鳞状上皮内高度病变（HSIL）、381例子宫颈鳞状上皮内低度病变（LSIL）和2584名正常对照组。建立非条件logistic回归模型，计算中国不同子宫颈病变的HPV总感染率，并计算18种HPV（6、16、18、31、33，35、39、45、51、52、56、58、59、66、68、70、73和82）型别感染率。 结果：在浸润性子宫颈癌、子宫颈鳞状上皮内高度病变、子宫颈鳞状上皮内低度病变和正常对照中，总HPV调整感染率分别为82．7％、88．5％、69．3％和13．1％。所有宫颈状态中，HPVl6型为最常见的HPV型别，在浸润性子宫颈癌中，占第2、3位的依次为HPV18型和58型；在子宫颈鳞状上皮内高度病变、子宫颈鳞状上皮内低度病变和正常组中分别为HPV58型和52型。在浸润性子宫颈癌中，HPVl6、18、58、52和31型是最常见的5种HPV型别。HPVl6／18型在浸润性子宫颈癌、子宫颈鳞状上皮内高度病变、子宫颈鳞状上皮内低度病变和正常子宫颈中的感染率依次为69．6％、59．1％、32．3％和4．4％。 结论：估计HPVl6／18型疫苗对中国的子宫颈癌有高达69．6％的预防作用
——《中国妇女子宫颈人乳头瘤病毒型别分布的Meta分析》 2007年10月，中华流行病学杂志上海地区尖锐湿疣以HPV6和HPV11感染为主。高危型HPV感染中最常见的3种亚型依次为HPV16、HPV52和HPV18。 由于高危型HPV 感染与癌症的关系密切，并且不同地区人群HPV 亚型的分布不同，因此了解HPV基因型的分布情况对疫苗的研制有重要意义。本研究发现，高危型HPV通常存在于多重感染中，如HPV16多与HPV6、11、52混合感染，HPV52多与HPV11、16混合感染，HPV18则多与HPV6、31混合感染。在法国，常见的高危型有HPV16、18、3；在韩国，常见的高危型是HPV16、58、33、31。本研究发现，上海地区主要的高危型为HPV16、52、18，与亚洲地区HPV52、58感染率较高的报道相符，为上海地区HPV疫苗的研制提供了相关信息。 ——《应用液相芯片技术对上海地区尖锐湿疣患者进行人乳头瘤病毒分型》 2009年《上海医学》贺国丽等对海南300例宫颈癌妇女进行了HPV检测发现：HPV阳性率商达94．oo％，且均为高危型，其中以16 和1 8型占绝对优势，分别占69．68％、16．49％。 ——《人乳头瘤病毒检测在宫颈病变筛查中的作用》二、结论
附件3 人乳头瘤病毒（HPV）核酸检测及基因分型、 试剂技术审查指导原则 本指导原则旨在指导注册申请人对人乳头瘤病毒（HPV）核酸检测及基因分型试剂注册申报资料的准备及撰写，同时也为技术审评部门审评注册申报资料提供参考。 本指导原则是针对人乳头瘤病毒（HPV）核酸检测及基因分型试剂的一般要求，申请人应依据产品的具体特性确定其中内容是否适用，若不适用，需具体阐述理由及相应的科学依据，并依据产品的具体特性对注册申报资料的内容进行充实和细化。 本指导原则是供申请人和审查人员使用的指导性文件，不涉及注册审批等行政事项，亦不作为法规强制执行，如有能够满足法规要求的其他方法，也可以采用，但应提供详细的研究资料和验证资料。应在遵循相关法规的前提下使用本指导原则。 本指导原则是在现行法规、标准体系及当前认知水平下制定的，随着法规、标准的不断完善和科学技术的不断发展，本指导原则相关内容也将适时进行调整。 一、范围 人乳头瘤病毒（Human Papillomavirus, HPV）属于乳头瘤病毒科，是一种小分子的、无被膜包被的1、环状双链DNA病毒，基因组
长约8000碱基对（bp），分为3个功能区，即早期转录区（E区）、晚期转录区（L区）和非转录区（长控制区，LCR）。HPV通过直接或间接接触污染物品或性传播感染人类。该病毒不但具有宿主特异性，而且具有组织特异性，只能感染人的皮肤和粘膜上皮细胞，引起人类皮肤的多种乳头状瘤或疣及生殖道上皮增生性损伤。 对于感染生殖道和肛门的HPV，根据各基因型别致病力大小或致癌危险性大小可分为低危型和高危型两大类。在有性生活史的女性中生殖道HPV感染具有普遍性，据统计70%～80%的女性在其一生中会有至少一次的HPV感染，但大多数感染为自限性，超过90％的感染的女性会出现一种有效的免疫应答，在没有任何长期的健康干预时在6到24个月之间可以清除感染。而持续性的高危型HPV感染则是导致宫颈上皮内瘤变及宫颈癌的主要原因。全球范围的研究结果显示，在%的宫颈癌患者体内检测到高危型HPV DNA的存在，其中HPV16型、18型、45型和31型感染占80%。低危型HPV一般与尖锐湿疣或低度鳞状上皮内病变相关，极少引起浸润癌。关于高危型与低危型的划分，国际上许多机构都给出了参考建议，依据WHO国际癌症研究机构（IARC）及其他国际组织的研究成果，本指导原则建议将HPV16、18、31、33、35、39、45、51、52、56、58、59、68等13种基因型列为高危型别，26、53、66、73、82等5种基因型列为中等风险型别，本指导原则中所述的检测试剂及其要求均只针对用于宫颈癌
含山县人民医院 人乳头瘤病毒（HPV）基因分型检测报告 姓名：陈俊科室：妇产科病历号： 性别：女房/床号：339床标本编号： 年龄： 44 送检医生：陈开芳接收日期：2015/12/24 电话：门诊/住院号：标本条码号： 临床诊断： 标本类型：宫颈脱落细胞标本状态：正常 检测方法：分子杂交法 检测内容：高危型：HPV16、18、31、33、35、39、45、51、52、53、56、58、59、66、68、 73、83、82 低危型：HPV6、11、42、43、81 检测结果： 高危型：阴性 低危型：阴性 结果分析及提示： ●HPV感染是宫颈癌的主要病因,大部分HPV感染会自行消退,与年龄及个人免疫能力有关。 ●HPV基因分型检测是宫颈病变及宫颈癌筛查的重要手段。 ●低危型HPV感染能引起良性病变，如生殖器湿疣。 ●高危型HPV感染可导致恶性病变，最终可发展为浸润性宫颈癌。 检测日期：2015/12/26 检测者： 审核者： 备注：本报告仅对所检测标本负责。 含山县人民医院 人乳头瘤病毒（HPV）基因分型检测报告 姓名：杨艳科室：妇产科病历号： 性别：女房/床号：标本编号： 年龄： 28 送检医生：陈开芳接收日期：2015/12/28 电话：门诊/住院号：标本条码号： 临床诊断： 标本类型：宫颈脱落细胞标本状态：正常 检测方法：分子杂交法 检测内容：高危型：HPV16、18、31、33、35、39、45、51、52、53、56、58、59、66、68、 73、83、82
低危型：HPV6、11、42、43、81 检测结果： 高危型：阴性 低危型：阴性 结果分析及提示： ●HPV感染是宫颈癌的主要病因,大部分HPV感染会自行消退,与年龄及个人免疫能力有关。 ●HPV基因分型检测是宫颈病变及宫颈癌筛查的重要手段。 ●低危型HPV感染能引起良性病变，如生殖器湿疣。 ●高危型HPV感染可导致恶性病变，最终可发展为浸润性宫颈癌。 检测日期：2015/12/31 检测者： 审核者： 备注：本报告仅对所检测标本负责。 含山县人民医院 人乳头瘤病毒（HPV）基因分型检测报告 姓名：黄传红科室：妇产科病历号： 性别：女房/床号：标本编号： 年龄： 38 送检医生：陈开芳接收日期：2015/12/28 电话：门诊/住院号：标本条码号： 临床诊断： 标本类型：宫颈脱落细胞标本状态：正常 检测方法：分子杂交法 检测内容：高危型：HPV16、18、31、33、35、39、45、51、52、53、56、58、59、66、68、 73、83、82 低危型：HPV6、11、42、43、81 检测结果： 高危型：阴性 低危型：阴性 结果分析及提示： ●HPV感染是宫颈癌的主要病因,大部分HPV感染会自行消退,与年龄及个人免疫能力有关。 ●HPV基因分型检测是宫颈病变及宫颈癌筛查的重要手段。 ●低危型HPV感染能引起良性病变，如生殖器湿疣。 ●高危型HPV感染可导致恶性病变，最终可发展为浸润性宫颈癌。 检测日期：2015/12/31 检测者： 审核者： 备注：本报告仅对所检测标本负责。
A Introduction of HPV Vaccine By 曹瑞灿 刘庆刚 吴宗龙 张丽萍
Abstract A vaccine is a biological preparation that provides active acquired immunity to a particular disease. The administration of vaccines is called vaccination. Vaccination is the most effective method of preventing infectious diseases .As long as the vast majority of people are vaccinated, it is much more difficult for an outbreak of disease to occur, let alone spread. HPV vaccine was first developed by the University of Queensland in Australia .The two main kinds of HPV vaccine are Gardasil and Cervarix. In July 18, 2016, Cervarix had been approved by China Food and Drug Administration (CFDA), therefore became the first approved HPV vaccine in China. Cervarix is mainly aimed at HPV16 and 18 prevention.HPV16, 18 infection can lead to cervical cancer and precancerous lesions. More than 70% of cervical cancer is caused by these two viruses .So far ,HPV vaccine is the only vaccine that can prevent cancer The part four mainly introduces the indications and the contraindication efficiency of HPV vaccine. Key words: HPV vaccine; HPV; Cervarix; cervical cancer