51. Inflammations, tumourlike lesions and tumours of the cervix. Carcinoma of the cervix (pathogenesis, pathomorphology, screening)

Cervix?

Neck of uterus, divided into:

- Exocervix - covered by stratified squamous epithelium

- Endocervix - simple columnar epithelium

= Junction between them is called squamocolumnar junction

Cervicitis?

Inflammation of the cervix

- Can be infectious or non-infectious

- Most frequently caused by STD

Most important causes for cervicitis?

Infectious:

- Chlamydia trachomatis

- Neisseria Gonorrhea

- HSV-2

- Trichomonas vaginalis

Non-infectious:

- Local trauma

- Chemical irritation

How does cervicitis present?

- Red swollen cervix

- Vaginal discharge

- Pain during sex

Infection may spread to upper genital tract, causing pelvic inflammatory disease

Cervical cancer?

Virtually all cases are caused by HPV

- Virus infects the lower genital tract -> especially at the squamocolumnar junction

What can HPV infection of the cervix lead to?

Most are cleared by the immune system

- Some are not cleared, and will progress into Cervical Intraepithelial Neoplasia - CIN

Risk factors for cervical cancer?

Same as for HPV-infection:

- Early onset of sexual activity

- Multiple sexual partners

- Immunosuppression

- Smoking

HPV subtypes associated with cervical cancer?

High-risk HPV:

- 16, 18, 21 and 33

They integrate their genome into the host cell genome, and start expressing proteins

- HPV produce two potent oncoproteins: E6 and E7

What does E6 and E7 do in papillomavirus?

- E6 inhibit p53

- E7 inhibit pRb

Will promote growth and increase the susceptibility to additional mutations that may eventually lead to CIN -> invasive cancer

The progression of CIN into invasive cancer?

HPV is necessary for the development of CIN, but the virus cannot progress CIN into invasive cancer

- Smoking

- Immune status

- Hormonal status

- Mutations in genes like LKB

... plays a role in the progression of CIN -> invasive cancer

CIN grading?

CIN I

- Low-grade dysplasia

- In the lower 1/3 of the exocervix are dysplastic

CIN II and later III

- High-grade dysplasia

- 2/3 and then all layers are dysplastic

Major sign of HPV infection?

Koilocytic change

- Presence of koilocytes - squamous epithelial cells that have been infected by HPV

- They have irregular nucleus

- Clear area around the nucleus -> called perinuclear halo

How many of CIN II and III will progress into invasive carcinoma?

Only 10% will progress into invasive carcinoma within 10 years

What type of cancers affect the cervix?

- Squamous cell carcinoma - 75%

- Adenocarcinoma & mixed adenosquamous - 20%

- Neuroendocrine - less than 5%

Pap smear?

Detects presence of atypical cells and koilocytes

- Spatula scrape epithelial cells from ectocervix and endocervix

- Screen women bw. 20-60y/age

Test should be performed every 3-5 years

Is better at detecting squamous cell carcinoma than adenocarcinoma

Specificity of pap smear?

The pap smear has high specificity, but low sensitivity

(Means that there are few false positive results, but there may be false negatives)

- So the test should be repeated every few years

What should be done if the pap smear yields positive results?

- HPV testing

- Colposcopy

- Biopsy

may be performed

Cone biopsy?

Surgical removal of a cone-shaped section of the cervix

- Performed on women with high-grade CIN

HPV vaccine?

Protect against HPV subtypes 16 and 18

Effective for protecting against genital warts and cervical cancer

Has lately been offered to young boys as well, to prevent HPV-induced cancers of penis, rectum and upper respiratory tract

Why does the HPV-vaccine not remove the need for routine screening?

- 16 and 18 are not the only high-risk strains of HPV

- If you are already infected by HPV before vaccination, it does not give significantly protection

Invasive cervical cancer develops in?

Women who never had a Pap smear

or

Who have not been screened for many years

What does invasive cervical cancer present with?

- Unexpected vaginal bleeding

- White vaginal discharge

- Painful sexual activity

- Dysuria

Treatment - cervical cancer?

- Hysterectomy

- Lymph node dissection

(If the cancer is small/barely invades - it can be treated with cone biopsy)

Common cause of death with cervical cancer?

Renal failure due to obstruction of the urinary bladder or ureters