Masaryk University Schol of Medicine and Brno University Hospital Department of Obstetrics and Gynecology Head: Prof. Pavel Ventruba, DrSc.,MBA General Medicine Obstetrics and Gynecology Seminary 2017 – 2018 – Autumn Semester Cervical dysplasia •founded 150 types of HPV •about 40 specific types of HPV - affinity the genitals (cervix, vulva, vagina, perianal area, penis) •500 000 new cases of invasive cervical cancer / year in the world (association with HR HPV positivity) Biology ØDNA viruses (papovaviridae) Øepiteliotrophia, proliferrative effect Øaccording to the specificity of tissue Ø - skin - mucosal Øaccording to the oncogenic potential Ø - LR (low risk) - 6,11 (42,43,44) Ø - HR (high risk) - 16,18 (31,33,35,39,45,51) Geographic distribution (cervical cancer) ØEurope, N. America, N. Africa - type 16 ØAsia - type 18 ØSub-saharan Africa - type 45 ØM. and S. Amerika - type 31 ØCzech republic - type 16(60-65%) Ø - type 18(15-20%) Ø - the others Ø - glandular precancerosis - type 18 The mechanism of action of oncogenic • inactivation of tumor suppressor genes • HPV genome encodes viral proteins E1- E7 E6 - nuclear protein p53 E7 - retinoblastom protein RB • viral DNA - benign lesions, precancerosis - episomal (extrachromosomal) - malignancies - integration to the genome Risk factors • risky sexual behaviour, early start of sexual life (infection of unmature metaplastic epithelium „high malignant potential“) • immunosuppression • smoking, STD, multiple parity • hormonal contraception (long term use) - persistence HPV, extensive TZ (transformation zone) Transmission of infection Ø: microtrauma, direct contact in places Ø transition epiteliums - cervix (nasopharynx, Ø epiglottis, anus..) Ø Øsexual intercourse (mostly) Øindirect contamination Øvertically (mother – fetus) Ø(transplacental transmission) Ø Ø Ø The fate of infection – regresion, persistence, progression : 70-80% of women - contact with HPV infection : spontaneous clearance of the virus (excluding from the body in women with latent infection is to a certain age) : 18-25 aged - 25% of women - HR HPV positive : 35 aged - 3-5% of women with persistense HR HPV positivity - high risk of precancerosis and cancer HPV in gynecology Ø Ø Forms of infection : Ø ØCLINICAL (MANIFEST) ØSUBCLINICAL ØLATENT Ø Ø Ø Ø A/ Clinical (manifest) form - genital warts - HPV 6,11 - vulva (vagina, cervix, perianal area) Morphology - condylomata accuminata - smooth papular warts - flat warts 223 225 227 228 Diagnosis - macroscopic finding - kolposcopy - histology NEED histological finding !!! Therapy - elimination of virus very difficult, persistence of HPV pozitivity up to 45% Conservative therapy ØImiguimod (Aldara) - unguent ØPhodophyllotoxin (Wartec) - unguent ØPodophyllin - local solution ØTrichloroacetic acid - local solution ØInterferon alfa - injection ØPhotodynamic therapy - sensitization Ø 5-aminolevul acid and effect certain wave- Ø lengths of the visible spectrum Surgical treatment Øablation (spoon, curette) Øexcision Øelectrocoagulation Ølaser B/ Subclinical form in the cervix - separately or associated with CIN or cancer (up to 98%) Dignosis: 1. COLPOSCOPY - a prominent JOD negative lesions - papilary, fingerely, flat (called brain-like area) 235 238 2. PAP test – KOILOCYT According to the BETHESDA system - SIL : LG SIL/HPV – genital warts, CIN I : HG SIL - CIN II, III LBC (Liquid Based Cytology) - possibility currently HR HPV testing 3.HISTOLOGY - acanthosis, hyperkeratosis, parakeratosis, presence of koilocyts C/ Latent form - without clinical manifestations - HPV DNA detection : amplification methods (PCR) - research : hybridization methods - qualitative determination of virus DNA, resoluton LR and HR (a smear of the cervix using the sampling kit) Therapy Øviral lesions separate or combined with Ø CIN I - 40-80% of spontanneous Ø regression Ø - observation Ø - destructive methods - electrocoagulation Ø - laser technology Ø - cryotherapy Ø INDICATION: exocervical lesions Ø HISTOLOGY FINDINGS ALWAYS Ø REQUIRED !!! Histological findings CIN II,III - excision methods - radio(electro)surgery : LETZ, LLETZ (disection of exocervix) : NETZ (dissection of endocervix) : SWETZ LETZ LETZ2 konizacejehlou cyldisendocerv Others excisional techniques - „cold knife“ cone - laser technology - combination of excision and destructive techniques Ø Thank you for your attention !