医学检验学（PPT讲稿）Molecular diagnosis and monitoring of HPV infection

Molecular diagnosis andmonitoring of HPV infection2

Molecular diagnosis and monitoring of HPV infection 2

HPVPapillomaviridae familyNon-enveloped50-55 nm, icosahedral capsidLCRE6E7Circular genome, dsDNA virus7.905L1>100 HPV types7.0001.00D)-BasedonL1genesequenceE1HPV166.0002.000-HPVsubtypes2-10%3.0006.000-HPVvariants<2%4.000L2E2E4

HPV • Papillomaviridae family • Non-enveloped • 50-55 nm, icosahedral capsid • Circular genome, dsDNA virus • >100 HPV types – Based on L1 gene sequence – HPV subtypes 2-10% – HPV variants <2%

Mucosal HPV typesOncogenityHPV typesHigh risk HPV types16, 18,31,33,3539, 45, 52, 56, 58, 5967, 68, 70LowriskHPVtypes6,11,40,42,43,4454, 61, 70, 72, 74, 81,83, 84Probable high risk26, 51, 53, 56, 66, 6982types

Oncogenity HPV types High risk HPV types 16, 18, 31, 33, 35, 39, 45, 52, 56, 58, 59, 67, 68, 70 Low risk HPV types 6, 11, 40, 42, 43, 44, 54, 61, 70, 72, 74, 81, 83, 84 Probable high risk types 26, 51, 53, 56, 66, 69, 82 Mucosal HPV types

Productive infection- HPV replicationKeratinocytesrelease2N0Stratumcorneum一StratumgranulosumStratumspinosum+E1,E2Basalcells20-100HPVDNA/cell

Stratum corneum Stratum granulosum Stratum spinosum Basal cells E 1, E2, E4, E5,E6,E7 E1, E2 20-100 HPV DNA/cell E4, L 1, L 2 >1000 HPV DNA /cell Keratinocytes release Productive infection- HPV replication

HPV associated cancers12,000FemalesMales10,000asie8,0006.0004,0002,000PenisCervixVulvaVaginaAnusHeadandNeck*CancerSite

HPV associated cancers

Prevalence of HpV cervical infectionIn women in the world:25-HPV infection prevalence 2-44%-HR HPV prevalence 15.1%202Age (years)-≥ 30 age HR HPV prevalence 5-10%HPV 16 is most common type inwomen with normal cervical cytology But cervical cancer is a rarecomplication of HPV infectionBasemanJG,etal.JClinVirol2005,32S;16-24

Prevalence of HPV cervical infection • In women in the world: –HPV infection prevalence 2-44% –HR HPV prevalence 15.1% – ≥ 30 age HR HPV prevalence 5-10% • HPV 16 is most common type in women with normal cervical cytology • But cervical cancer is a rare complication of HPV infection Baseman JG, et al. J Clin Virol 2005, 32S;16-24

HPV associated Cervical CancerPersistentHPVInfectionTransientInfectionMild cytologicHPVabnormalitiesInitialinfection10-15yProgressionInvasionNormal cervixHPV-infected cervixPrecancerousCancerlesionRegressionClearance80%25201b20(%)rd00oood12HPV15Cancer100500443n095-24o655NEJM348:518-527.200315-50354050-683Age (years)

HPV associated Cervical Cancer NEJM 348:518-527, 2003 80% 10-15 y

Head and neck cancersEpidemiology of HNSCC-50,000newcases/y- 13,000 deaths/ySubdivision by locationNasal Cavity-Nasopharynx-Oral CancerTongueOropharynx- Laryngeal CancerEsophagusLarynx- Nasopharyngeal CancerTracheaHistology types- SCC. Keratinized·Non-keratinized- NPC

Head and neck cancers • Epidemiology of HNSCC – 50,000 new cases/y – 13,000 deaths/y • Subdivision by location – Oral Cancer – Laryngeal Cancer – Nasopharyngeal Cancer • Histology types – SCC • Keratinized • Non-keratinized – NPC

Biological and clinical characteristics of HNScCHNSCC20%HPV80%HPVE6andE7positiveMostlyoropharynx65%highCIN15%lowCINMainlywild-typeTP53FavourableprognosisMany numerical changesFewnumerical changesMainlyaneuploidNeardiploidMainlymutatedTP53Mainlywild-typeTP53Favourableprognosis?LessfavourableprognosisTable1|Different clinicaland biological characteristicsof HPV-negativeand HPV-positiveHNSCCRefsFeatureHPV-negative HNSCCHPV-positiveHNSCCIncidenceDecreasingIncreasing138,13931AetiologyOralsexSmoking,excessivealcoholuseAge138Above60yearsUnder60yearsYesUnknown49,136FieldcancerizationTP53mutationsFrequentInfrequent26,27,140NonePredilection siteOropharynx21,141PoorFavourablePrognosis5,142HNSCC,headandnecksquamouscellcarcinoma;HPV,humanpapillomavirus

Biological and clinical characteristics of HNSCC

Anal cancer~0.16% of men and women born today willhave cancer of the anus, anal canal, oranorectum sometime during their life·Approx5260new cases annuallyin US- 2000 in men and 3260 in w0men· Anal canal lesions may have more aggressivebiology

Anal cancer • ~0.16% of men and women born today will have cancer of the anus, anal canal, or anorectum sometime during their life • Approx 5260 new cases annually in US – 2000 in men and 3260 in women • Anal canal lesions may have more aggressive biology