Gynaecological cancer Flashcards
What are the cell types of cervical cancer?
80% squamous cell carcinoma
next MC is adenocarcinoma
what cancer is HPV associated with?
cervical
anal, vulval, vaginal, penis, mouth and throat cancers
what are the 2 important strains of HPV?
type 16 and 18, vaccine targets them
cause 70% of cervical cancer
what is the pathophysiology of HPV causing cervical cancer?
P53 and pRb are tumour suppressor genes.
HPV (types 16 and 18) produces two proteins (E6 and E7) that inhibit these tumour suppressor genes.
The E6 protein inhibits p53
E7 protein inhibits pRb. Therefore, HPV promotes the development of cancer by inhibiting tumour suppressor genes.
less common risk factors of cervical cancer?
Smoking
HIV (patients with HIV are offered yearly smear tests)
Combined contraceptive pill use for more than five years
Increased number of full-term pregnancies
Family history
Exposure to diethylstilbestrol during fetal development (this was previously used to prevent miscarriages before 1971)
what appearance of the cervix makes you think cancer?
Ulceration Inflammation Bleeding Visible tumour --> urgent refer for colposcopy
How do you diagnose CIN?
Cervical intraepithelial neoplasia (CIN) is a grading system for the level of dysplasia (premalignant change) in the cells of the cervix. CIN is diagnosed at colposcopy (not with cervical screening)
TOM TIP: Try not to get mixed up between dysplasia found during colposcopy and dyskaryosis on smear results.
3 grades of CIN
CIN I: mild dysplasia, affecting 1/3 the thickness of the epithelial layer, likely to return to normal without treatment
CIN II: moderate dysplasia, affecting 2/3 the thickness of the epithelial layer, likely to progress to cancer if untreated
CIN III: severe dysplasia, very likely to progress to cancer if untreated
CIN III is sometimes called cervical carcinoma in situ.
How often do you screen for cervical cancer? what are the exceptions?
Every three years aged 25 - 49
Every five years aged 50 - 64
Women with HIV are screened annually
Women over 65 may request a smear if they have not had one since aged 50
Women with previous CIN may require additional tests (e.g. test of cure after treatment)
Certain groups of immunocompromised women may have additional screening (e.g. women on dialysis, cytotoxic drugs or undergoing an organ transplant)
Pregnant women due a routine smear should wait until 12 weeks post-partum
what can the cytology results from cervical smear show?
Inadequate Normal Borderline changes Low-grade dyskaryosis High-grade dyskaryosis (moderate) High-grade dyskaryosis (severe) Possible invasive squamous cell carcinoma Possible glandular neoplasia
infections may be identified
what organism is discovered in women with the coil?
Actinomyces-like organisms are often discovered in women with an intrauterine device (coil). These do not require treatment unless they are symptomatic. Where the woman is symptomatic (e.g. pelvic pain or abnormal bleeding), removal of the intrauterine device may be considered.
What is Colposcopy?
It involves inserting a speculum and using equipment (a colposcope) to magnify the cervix. This allows the epithelial lining of the cervix to be examined in detail. During colposcopy, stains such as acetic acid and iodine solution can be used to differentiate abnormal areas.
A punch biopsy or large loop excision of the transformational zone can be performed during the colposcopy procedure to get a tissue sample.
what does acetic acid and iodine do on colposcopy?
Acetic acid causes abnormal cells to appear white = acetowhite.
–> This occurs in cells with an increased nuclear to cytoplasmic ratio (CIN, cancer)
Schiller’s iodine test involves using an iodine solution to stain the cells of the cervix. Iodine will stain healthy cells a brown colour. Abnormal areas will not stain.
What is a LLETZ procedure?
A large loop excision of the transformation zone aka a loop biopsy.
- under LA on colposcopy
- use a loop of wire with electrical current (diathermy) to remove abnormal epithelial tissue on the cervix. The electrical current cauterises the tissue and stops bleeding.
Bleeding and abnormal discharge can occur for several weeks following a LLETZ procedure. This varies between women. Intercourse and tampon use should be avoided after the procedure to reduce the risk of infection. Depending on the depth of the tissue removed from the cervix, the procedure may increase the risk of preterm labour.
what obstetric complication can occur after a LLETZ procedure?
preterm labour - depend son depth of tissue removed
What is a cone biopsy used for?
treatment forCIN and very early-stage cervical cancer.
- under GA
The surgeon removes a cone-shaped piece of the cervix using a scalpel. This sample is sent for histology to assess for malignancy.
Main risks of a cone biopsy
Pain
Bleeding
Infection
Scar formation with stenosis of the cervix
Increased risk of miscarriage and premature labour
what staging is used for cervical cancer?
The International Federation of Gynaecology and Obstetrics (FIGO) staging system is used to stage cervical cancer:
Stage 1: Confined to the cervix
Stage 2: Invades the uterus or upper 2/3 of the vagina
Stage 3: Invades the pelvic wall or lower 1/3 of the vagina
Stage 4: Invades the bladder, rectum or beyond the pelvis
what strains does the HPV vaccine protect against?
NHS - Gardasil
6, 11, 16, 18
Strains 6 and 11 cause genital warts
Strains 16 and 18 cause cervical cancer
what is the most common cell type of endometrial cancer?
80% adenocarcinoma
oestrogen-dependent cancer, meaning that oestrogen stimulates the growth of endometrial cancer cells.
postmenopausal and bleeding =
endometrial cancer until proven otherwise
- key risk factors = obesity and DM
What is endometrial hyperplasia?
Precancerous condition = thickening of the endometrium.
The risk factors, presentation and investigations of endometrial hyperplasia are similar to endometrial cancer.
Most cases of endometrial hyperplasia will return to normal over time.
< 5% –> become endometrial cancer.
2 types of endometrial hyperplasia to be aware of:
Hyperplasia without atypia
Atypical hyperplasia
how can you treat endometrial hyperplasia?
progestogens,
--> Intrauterine system (e.g. Mirena coil)
Continuous oral progestogens (e.g. medroxyprogesterone or levonorgestrel)
what hormone causes endometrial cancer?
oestrogen-dependent cancer, meaning that oestrogen stimulates the growth of endometrial cancer cells.
risk factors of endometrial cancer
Primary risk factor is unopposed estrogen (i.e. no progesterone) exposure w/ resultant hyperplasia.
- inc age
- oestrogen only HRT
- Tamoxifen
- Early Menarche
- Late menopause
- Anovulatory cycles (so no progesterone from corpus lutem) (PCOS, perimenopause)
- Nulliparity
- Obesity
- Diabetes
- HNPCC or Lynch syndrome
- Gallbladder Disease
- Physical Inactivity
- High-fat, low-fiver diet
- Hypertension
- Family history
what should women with PCOS be managed with for endometrial protection?
one of:
- COCP
- Mirena coil
- Cyclical progestogens to induce a withdrawal bleed.
why is obesity a risk factor for endometrial cancer?
Adipose tissue (fat) is a source of oestrogen. Adipose tissue is the primary source of oestrogen in postmenopausal women. Adipose tissue contains aromatase, which is an enzyme that converts androgens such as testosterone into oestrogen. --> make more oestrogen
This extra oestrogen is unopposed in women that are not ovulating (e.g. PCOS or postmenopause), because there is no corpus luteum to produce progesterone.
what effect does tamoxifen have on breast tissue and endometrium?
anti-oestrogenic effect on breast tissue, but an oestrogenic effect on the endometrium. This increase the risk of endometrial cancer.
protective factors against endometrial cancer
COCP
Mirena coil
Increased pregnancies
Cigarette smoking
Smoking appears to be anti-oestrogenic. (only on endometrium so not breast)
referral criteria for endometrial cancer
2-week-wait urgent cancer referral for endometrial cancer is: Postmenopausal bleeding (more than 12 months after the last menstrual period)
NICE also recommends referral for a transvaginal ultrasound in women over 55 years with:
Unexplained vaginal discharge
Visible haematuria plus raised platelets, anaemia or elevated glucose levels
3 investigations to diagnose endometrial cancer
- Transvaginal ultrasound for endometrial thickness (normal is < 4mm post-menopause)
- Pipelle biopsy, which is highly sensitive for endometrial cancer making it useful for excluding cancer
- outpt clinic
- tube into uterus, take endometrial sample
- quick, less invasive - Hysteroscopy with endometrial biopsy
Depending on local guidelines, a normal transvaginal ultrasound (endometrial thickness < 4mm) and normal pipelle biopsy are sufficient to demonstrate a very low risk of endometrial cancer and discharge the patient.
Staging of endometrial cancer
The International Federation of Gynaecology and Obstetrics (FIGO) staging system is used to stage endometrial cancer:
Stage 1: Confined to the uterus
Stage 2: Invades the cervix
Stage 3: Invades the ovaries, fallopian tubes, vagina or lymph nodes
Stage 4: Invades bladder, rectum or beyond the pelvis
what is management of endometrial cancer?
total abdominal hysterectomy with bilateral salpingo-oophorectomy, = TAH + BSO (removal of uterus, cervix and adnexa).
Other treatment options depending on the individual presentation include:
A radical hysterectomy involves also removing the pelvic lymph nodes, surrounding tissues and top of the vagina
Radiotherapy
Chemotherapy
Progesterone may be used as a hormonal treatment to slow the progression of the cancer
Why does ovarian cancer have a poor prognosis?
Specific signs rarely appear until after secondary tumors have developed
presents late due to the non-specific symptoms, resulting in a worse prognosis. More than 70% of patients with ovarian cancer present after it has spread beyond the pelvis.
what’s the most common type of ovarian cancer?
epithelial cell tumour
- subtype serous tumours MC
also subtypes: Endometrioid carcinomas Clear cell tumours Mucinous tumours Undifferentiated tumours
what is a Krukenberg tumour and its sign on histology?
metastasis in the ovary, usually from a gastrointestinal tract cancer, particularly the stomach.
Krukenberg tumours have characteristic “signet-ring” cells on histology
risk factors for ovarian cancer
Age (peaks age 60) BRCA1 and BRCA2 genes (consider the family history) Increased number of ovulations Obesity Smoking Recurrent use of clomifene
Factors that increase the number of ovulations, increase the risk of ovarian cancer. These include:
Early-onset of periods
Late menopause
No pregnancies
why can you get hip or groin pain with ovarian cancer?
An ovarian mass may press on the obturator nerve and cause referred hip or groin pain. The obturator nerve passes along the inside of the pelvic, lateral to the ovaries, where an ovarian mass can compress it.
referral criteria for ovarian cancer? 2 WW and also initial Ix in primary care
Refer directly on a 2-week-wait referral if a physical examination reveals:
Ascites
Pelvic mass (unless clearly due to fibroids)
Abdominal mass
Carry out further investigations before referral in women presenting with symptoms of possible ovarian cancer, starting with a CA125 blood test. This is particularly important in women over 50 years presenting with:
New symptoms of IBS / change in bowel habit
Abdominal bloating
Early satiety
Pelvic pain
Urinary frequency or urgency
Weight loss
Staging of ovarian cancer
(FIGO) staging system is used to stage ovarian cancer. A very simplified version of this staging system is:
Stage 1: Confined to the ovary
Stage 2: Spread past the ovary but inside the pelvis
Stage 3: Spread past the pelvis but inside the abdomen
Stage 4: Spread outside the abdomen (distant metastasis)
managed with surgery and chemo, MDT
what are cell types of vulval cancer?
90% are squamous cell carcinomas.
Less commonly, they can be malignant melanomas.
vulval cancer risk factors
Advanced age (particularly over 75 years)
Immunosuppression
HPV infection
Lichen sclerosus (5% develop)
what is VIN
premalignant condition affecting the squamous epithelium of the skin that can precede vulval cancer. (similar to CIN)
High grade squamous intraepithelial lesion
- type of VIN associated with HPV infection that typically occurs in younger women aged 35 - 50 years.
Differentiated VIN
- alternative type of VIN associated with lichen sclerosus and typically occurs in older women (aged 50 - 60 years)
management of VIN
A biopsy is required to diagnose VIN.
Treatment options include: Watch and wait with close followup Wide local excision (surgery) to remove the lesion Imiquimod cream Laser ablation
where does vulval cancer most frequently affect?
labia majora, giving an appearance of: Irregular mass Fungating lesion Ulceration Bleeding
management of vulval cancer
2 ww diagnose: - biopsy - sentinel node biopsy (for LN spread) - stage with CT AP --> FIGO stage
Management depends on the stage, and may involve: Wide local excision to remove the cancer Groin lymph node dissection Chemotherapy Radiotherapy
