Cervix uteri

Cervix uteri

• anatomy• histology• ectopy / ectropion• Nabothian cysts• cervicitis• precancerous lesions• carcinoma

Anatomy

Cervix uteri - anatomy vaginal portion projects into the cavity of the vagina ectocervix / exocervix – the part of the cervix visible

from inside the vagina during a gynecologic examination

endocervix (endocervical canal) – a tunnel through the cervix

supravaginal portion the part of the cervix above the vaginal vault

• ectocervix – covered by stratified noncornified squamous epithelium

• endocervical canal – lined by single layer of mucin-secreting columnar epithelium

• squamocolumnar junction = the junction of the endocervical mucosa with the squamous epithelium

• transformation zone = part of the cercix covered by metaplastic squamous epithelium

Cervix - histology

• ectocervix – covered by stratified noncornified squamous epithelium

• endocervical canal – lined by single layer of mucin-secreting columnar epithelium

• squamocolumnar junction = the junction of the endocervical mucosa with the squamous epithelium

• transformation zone = part of the cercix covered by metaplastic squamous epithelium

Cervix - histology

• ectocervix – covered by stratified noncornified squamous epithelium

• endocervical canal – lined by single layer of mucin-secreting columnar epithelium

• squamocolumnar junction = the junction of the endocervical mucosa with the squamous epithelium

• transformation zone = part of the cercix covered by metaplastic squamous epithelium

Cervix - histologyEctopy/ectropion appears red and ulcerated to the naked eye – it also has been interpreted (mistakenly) as an erosion. But erosion is a different process accompanied by wearing away of the mucosal tissue.

causes of erosion:- trauma- chemicals- infections- carcinoma

Endocervical epithelium• is not exclusively limited to the anatomic area of endocervix• occupies significant regions of the anatomic ectocervix:• - especially at birth• - then after onset of puberty (mechanical reasons – swelling

of the stroma in response to hormonal stimulation)• - during pregnancy• - when using contraceptive pills• - after the delivery• - remains on the ectocervix until near the menopause

Squamous cell metaplasia• mucin-secreting endocervical epithelium is gradually

replaced by squamous epithelium• this area is known as the transformation zone• constant exposure to acidic vaginal pH levels are

triggers of the squamous metaplasia process (hyperplasia of the reserve cells – immature squamous metaplasia – mature squamous metaplasia)

• transformation zone is the most common area of pathological changes (dysplasia, inflammation, erosion)

Definition of metaplasia• metaplasia is 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

• metaplastic change is reversible and theoretically transformed epithelium should revert to its original form after the stimulus is removed but this does not always happen

• metaplasia occurs at many body sites eg. gastric mucosa, bladder, bronchi etc.

Nabothian cysts• mucinous retention cysts• develop within the TZ

secondary to squmous metaplasia, covering and obstructing endocervical glands

• up to 1.5 cm in diameter• usually disappear, some

can persist indefinitely• rarely can be

symptomatic

Cervicitis

Noninfectious cervicitis• chemical or mechanical in

nature• inflammatory response is

nonspecific• common causes:• - chemical irritation

(douching)• - local trauma (foreign

bodies – tampons, pessaries, IUD)

Infectious cervicitis• - common disease

• - central role in the pathogenesis of pelvic inflammatory disease and endometrial infections

• etiology:

• - bacteria

• - viruses

• - fungi

• - protozoa, parasites

Microorganism causing infectious cervicitis

• Bacteria• Chlamydia trachomatis• Neisseria gonorrhoeae• Mycoplasma hominis• Ureaplasma ureolyticum• Gardnerella vaginalis• Actinomyces israeli• Treponema pallidum• Mycobacterium tuberculosis• Group B Streptococcus

• Viruses• Human papillomavirus - HPV• Herpes simplex virus• Fungi• Candida albicans• Aspergillus• Protosoa and parasites• Trichomonas vaginalis• Ameba• Schistosomes

Infectious cervicitis• initial event of PID• primary infectious focus in

postpartum and postabortal endometritis

• concurrent bacterial infection have been directly related to:

• - spontaneous abortion• -premature delivery• - chorioamniitis• - stillbirth• - neonatal pneumonia and

septicemia

Precancerous lesions of the cervix

HPV• the most common cause of

sexually transmitted diseases (STD)

• infection by high-risk genotypes HPV plays a critical role in the pathogenesis of cancer:

• - cervix uteri• - vagina• - vulva• - anus• - penis• - orofacial region

• HPV includes about 130 genotypes to date

• 13 anogenital HPVs have been classified (by the IARC) as oncogenic – most common types:

• 16, 18, 31, 33, 51, 52, 53, 58

Epidemiology of HPV infection• most women become infected with HPV• frequent pattern: multiple serial infections with different

types of HPV, each infectious episode being of relatively short duration

• majority of HPV infections are transient – undergo clearence or become latent within 1-2 years

• high risk HPV tend to clear more slowly – the infection that persist for two or more years pose the gratest risk – since these are the infections that may progress to a high grade cervical precursor lesions or even an invasive cancer

Epidemiology of HPV infection• development of invasive cancer - after 10 or more years of

high-risk HPV persistent infection• high-grade CIN (CIN2, CIN3) – 30-50% of untreated lesions

progress to invasive cancer over a 30-year follow-up period

Molecular mechanisms of HPV-induced carcinogenesis

• high-risk types can integrate into the host genome• two viral genes (E6 and E7) may be over-expressed• E6 protein inhibits p53 (p53 controls responses to different

types of cellular stress including DNA damage)• E7 protein binds and inactivates Rb (Rb controls cell cycle

progression)

• selective growth advantage• continuous expression of these proteins can lead to the

accumulation of mutations in the cellular genome that are required for malignant conversion

high-risk HPV infection

viral integration

inactivation p53

inactivation Rb

loss of function (apoptosis, cycle cell checkpoints control)

loss of function(G1 to S phase transition, apoptosis)

transformation of the squamous (glandular) cells, genetic instability

precancerous lesions invasive carcinoma

80% transient infection

Cervical cancer prevention

Primary prevention• attempts to reduce the risk

of the actual development of HPV infection

• HPV vaccine• prevention of contact

with HPV• promotion, education

Secondary prevention• early detection and cure• screening• - early detection and

treatment of precancer or early invasive lesions

• PAP-smear• colposcopy• HPV test

Pathologic findings

• abnormal cellular proliferation

• abnormal maturation• cytologic atypia:• - nuclear pleomorphism• - increased N/C ratio• - hyperchromatic nuclei• - koilocytes• - increased mitotic activity

Carcinoma of the cervix

Invasive cervical cancer - risk factors

• infection with high-risk types of HPV• cigarette smoking • oral contraceptives• Chlamydia trachomatis infection• low socioeconomic status

• protective factors: vegetable (tomatoes – lycopene, carrots – carotenoids, folates…?)

Squamous cell carcinoma

• keratinizing• non-keratinizing• intercellular bridges• nuclear atypias• larger polygonal or oval cells• eosinophilic cytoplasm• usually numerous mitotic

figures

Adenocarcinoma

• mucinous• endometrioid • clear cell • serous

• histological features:• - glandular archtecture• - mucus production

(depends on histotype)

Prognostic factors

• stage is the most important prognostic factor• histologic type and grade – little direct

influence on survival• other prognostic factors:• - lymphvascular invasion (LVSI)• - tumor size (volume)• - depth of invasion• - parametrial involvement• - nodal status