Cervix uteri

1. Cervix uteri

2. Cervix uteri • anatomy • histology • ectopy / ectropion • Nabothiancysts • cervicitis • precancerouslesions • carcinoma

3. Anatomy

4. Cervix uteri - anatomy • vaginalportion • projectsintothecavityofthe vagina • ectocervix / exocervix–thepart of the cervix visible from inside the vagina during a gynecologic examination • endocervix (endocervicalcanal) – a tunnelthroughthe cervix • supravaginalportion • the part ofthe cervix abovethevaginalvault

5. Cervix - histology • ectocervix – covered by stratifiednoncornifiedsquamousepithelium • endocervicalcanal– lined by single layerof mucin-secretingcolumnarepithelium • squamocolumnarjunction= thejunctionoftheendocervicalmucosawiththesquamousepithelium • transformationzone= part ofthecercixcovered by metaplasticsquamousepithelium

6. Endocervicalepithelium • is not exclusively limited to theanatomic area ofendocervix • occupiessignificantregionsoftheanatomicectocervix: • - especiallyatbirth • - thenafteronsetof puberty (mechanicalreasons – swellingofthe stroma in response to hormonalstimulation) • - duringpregnancy • - whenusingcontraceptivepills • - afterthedelivery • - remains on theectocervixuntilnearthemenopause

7. Squamous cell metaplasia • mucin-secretingendocervicalepitheliumisgraduallyreplaced by squamousepithelium • this area isknown as thetransformationzone • constant exposure to acidic vaginal pH levels are triggers of the squamous metaplasia process (hyperplasiaofthereservecells – immaturesquamousmetaplasia – maturesquamousmetaplasia) • transformationzoneisthe most common area ofpathologicalchanges (dysplasia, inflammation, erosion)

8. Definitionofmetaplasia • metaplasiais process by which one fully differentiated type of epithelium changes into another • It is usually an adaptive change which occurs in in reaction to longstanding (chronic) irritation of any kind, or in response to hormonal stimuli • metaplasticchange is reversible and theoreticallytransformed epithelium should revert to its original form  after the stimulus is removed but this does not always happen • metaplasiaoccurs at many body sites eg.gastric mucosa, bladder,bronchi etc.

9. Nabothiancysts • mucinousretentioncysts • developwithinthe TZ secondary to squmousmetaplasia, covering and obstructingendocervicalglands • up to 1.5 cm in diameter • usuallydisappear, somecanpersistindefinitely • rarelycanbesymptomatic

10. Cervicitis Noninfectiouscervicitis Infectiouscervicitis - commondisease - central role in thepathogenesisofpelvicinflammatorydisease and endometrilainfections etiology: - bacteria - viruses - fungi - protozoa, parasites • chemicalormechanical in nature • inflammatory response isnonspecific • commoncauses: • - chemicalirritation (douching) • - local trauma (foreignbodies – tampons, pessaries, IUD)

11. Bacteria Chlamydiatrachomatis Neisseriagonorrhoeae Mycoplasmahominis Ureaplasmaureolyticum Gardnerellavaginalis Actinomycesisraeli Treponema pallidum Mycobacteriumtuberculosis Group B Streptococcus Viruses Humanpapillomavirus - HPV Herpes simplex virus Fungi Candidaalbicans Aspergillus Protosoa and parasites Trichomonasvaginalis Ameba Schistosomes Microorganismcausinginfectiouscervicitis

12. Infectiouscervicitis • initialeventof PID • primaryinfectiousfocus in postpartum and postabortal endometritis • concurrentbacterialinfectionhavebeendirectlyrelated to: • - spontaneousabortion • -prematuredelivery • - chorioamniitis • - stillbirth • - neonatalpneumonia and septicemia

13. Precancerouslesionsofthe cervix

14. Humanoncogenicviruses • viruses are associatedwithnearly 20% ofthehumancancercasesworldwide • the most common virus-associatedcancer : 1) cervicalcarcinoma 2) liver carcinoma

15. HPV includesabout 130 genotypes to date 13 anogenitalHPVshavebeenclassified (by the IARC) as oncogenic– most commontypes: 16, 18, 31, 33, 51, 52, 53, 58 HPV • the most common cause ofsexuallytransmitteddiseases (STD) • infection by high-riskgenotypes HPV plays a critical role in thepathogenesisofcancer: • - cervix uteri • - vagina • - vulva • - anus • - penis • - orofacial region

16. Epidemiology of HPV infection • most womenbecomeinfectedwith HPV • frequentpattern: multipleserialinfectionswithdifferenttypesof HPV, eachinfectiousepisodebeingofrelativelyshortduration • majority of HPV infections are transient – undergoclearenceorbecomelatentwithin 1-2 years • high risk HPV tend to clear more slowly – theinfectionthatpersistfortwoor more yearsposethegratest risk – since these are theinfectionsthatmayprogress to a high grade cervicalprecursorlesionsorevenaninvasivecancer

17. Epidemiology of HPV infection • developmentofinvasivecancer - after 10 or more yearsofhigh-risk HPV persistentinfection • high-grade CIN (CIN2, CIN3) – 30-50% ofuntreatedlesionsprogress to invasivecancerover a 30-year follow-up period

18. Molecular mechanismsof HPV-induced carcinogenesis • high-risk typescanintegrateintothe host genome • two viral genes (E6 and E7) may be over-expressed • E6 protein inhibits p53 (p53 controlsresponses to differenttypesofcellular stress including DNA damage) • E7 protein binds and inactivatesRb (Rbcontrols cell cycleprogression) • selectivegrowthadvantage • continuousexpression of these proteins can lead to the accumulation of mutations in the cellulargenome that are required for malignant conversion

19. Cervicalcancerprevention Primaryprevention Secondaryprevention screening - early detection and treatmentofprecanceror early invasivelesions PAP-smear colposcopy HPV test • HPV vaccine • preventionofcontactwith HPV • promotion, education

20. Pathologicfindings (dysplasia) • abnormalcellularproliferation • abnormalmaturation • cytologicatypia: • - nuclearpleomorphism • - increased N/C ratio • - hyperchromaticnuclei • - koilocytes • - increasedmitoticactivity

21. Pseudotumors CIN1,CIN2, CIN3, CIS Tumorsoftheuterine cervix • Precursorlesions • ancerouslesions • endocervicalpolyp • Benigntumors • Malignanttumors • fibroepithelial polyp • squamous cell papilloma • condylomaaccuminatum • leiomyoma • epithelial • squamous cell carcinoma • adenocarcinoma • mesenchymal • leiomyosarcoma

22. Carcinomaofthe cervix

23. Invasivecervicalcancer - risk factors • infectionwithhigh-risk typesof HPV • cigarette smoking • oral contraceptives • Chlamydiatrachomatisinfection • lowsocioeconomic status • protectivefactors: vegetable (tomatoes – lycopene, carrots – carotenoids, folates…?)

24. Incidence and mortality (Czech Republic 2007) source: http://www.uzis.cz

25. Worldwide incidence ofcervicalcancer • cervicalcanceris second only to breastcancer • most frequent type ofcancer in somedevelopingcountries • thirdleading cause ofcancer mortality source: http://info.cancerresearchuk.org

26. Squamous cell carcinoma • keratinizing • non-keratinizing • intercellularbridges • nuclearatypias • largerpolygonalor oval cells • eosinophiliccytoplasm • usuallynumerousmitoticfigures

27. Adenocarcinoma • mucinous • endometrioid • clear cell • serous • histologicalfeatures: • - glandulararchtecture • - mucusproduction (depends on histotype)

28. Prognosticfactors • stageisthe most importantprognosticfactor • histologic type and grade – little direct influence on survival • otherprognosticfactors: • - lymphvascularinvasion (LVSI) • - tumor size (volume) • - depthofinvasion • - parametrialinvolvement • - nodal status