Cancer - done Flashcards
Who does cervical cancer typically affect?
Younger women, peaking in reproductive years
What are the common types of cervical cancer?
Squamous cell carcinoma (80%)
Adenocarcinoma
Small cell cancer
What virus is cervical cancer typically associated with?
Human papillomavirus
When are children typically vaccinated against HPV?
Aged 12-13
What is the purpose of smear tests?
To screen for precancerous and cancerous changes to the cells of the cervix
What type of cancer is HPV associated with?
Cervical
Anal
Vulval
Vaginal
Penis
Mouth
Throat
What strains of HPV are responsible for cervical cancers?
Types 16 and 18
What is the treatment for HPV infection?
No treatment (most infections resolve within 2 years)
How does HPV cause cancer?
HPV produces two proteins E6 and E7 which inhibit tumour supressor genes p53 and pRb respectively
What are the types of risks for cervical cancer?
- Increased risk of catching HPV
- Later detection of precancerous or cancerous changes (non-engagement with screening)
- Other risk factors
What are the risks of catching HPV?
- Early sexual activity
- Increased number of sexual partners
- Sexual partners who have had more partners
- Not using condoms
What are the other risk factors for cerival cancer?
- Smoking
- HIV (patients with HIV are offered yearly smear tests)
- COCP use for more than 5 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 are the presenting symptoms of cervical cancer?
- Abnormal vaginal discharge (intermenstrual, postcoital or post-menopausal bleeding)
- Vaginal discharge
- Pelvic pain
- Dyspareunia (pain or discomfort with sex)
After taking a history suspicious of cervical cancer, what is the next step?
Examine the cervix with a speculum (during examination swabs can be taken to exclude infection)
What appearance on speculum is suggestive of cervical cancer?
- Ulceration
- Inflammation
- Bleeding
- Visible tumour
Urgent cancer referral for colposcopy should be made to assess further
If a smear test returns normally can that rule out cervical cancer?
No
What is cervical interaepithelial neoplasia?
A grading system for the level of dysplasia (premalignant change) in the cells of the cervix, its diagnosed at colposcopy (not with cervical screening)
What are the different grades of cervical intraepithelial neoplasia?
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
What is CIN III also known as?
Cervical carcinoma in situ
What is the difference between dysplasia found during colposcopy and dyskaryosis on smear results?
Who performs a smear test?
A practise nurse
What are precancerous cells also known as?
Dyskaryosis
What is the mode of transporting smear cells also known as?
Liquid-based cytology
What are the smear samples initially tested for?
High-risk HPV before the cells are examined, if the HPV test is negative then the person does not have HPV and the cells are not examined and the smear is considered negative
How often is the smear test done?
Every 3 years for those ages 25-49
Every 5 years for those aged 50-64
What are the exceptions to the smear screening schedule?
- 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 undergoing a routing smear should wait until 12 weeks post-partum
What are the possible cytology results to the smear test?
Inadequate
Normal
Borderline changes
Low-grade dyskaryosis
High-grade dyskaryosis (moderate)
High-grade dyskaryosis (severe)
Possible invasive squamous cell carcinoma
Possible glandular neoplasia
What other infections may be reported on the smear result?
- Bacterial vaginosis
- Candidiasis
- Trichomoniasis
When are actinomyces-like organisms found on a smear? Do they need treating?
Women with intrauterine devices (coil)
Do not require treatment unless they are symptomatic (e.g. pelciv pain or abnormal bleeding) - removal of the device may be considered
What are the possible management options of the smear test?
Inadequate sample – repeat the smear after at least three months
HPV negative – continue routine screening
HPV positive with normal cytology – repeat the HPV test after 12 months
HPV positive with abnormal cytology – refer for colposcopy
What does a colposcopy involve?
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 this stains such as acetic acid and iodine solution can be used to differentiate abnormal areas
What types of cells does acetic acid target and what is the colour change?
Cells with an increased nuclear to cytoplasmic ratio (more nuclear material) e.g. cervical intraepithelial neoplasia and cervical cancer cells
Abnormal cells appear white (acetowhite)
What does Schiller’s iodine test involve?
Using an iodine solution to stain the cells of the cervix - iodine will stain healthy cells a brown colour, abnormal cells will not stain
How can a tissue sample be obtained from a smear test?
Punch biopsy or large loop excision of the transformational zone can be performed during the colposcopy procedure
What is a large loop excision of the transformation zone (LLETZ) also known as?
Loop biopsy
How is a LLETZ performed?
Under local anaesthetic during a colposcopy with a loop diathermy to remove abnormal epithelial tissue on the cervix cauterising the tissue and stopping it from bleeding
What is the after care advice after a LLETZ?
Bleeding and abnormal dischage can occur for several weeks following a LLETZ procedure
Intercourse and tampons should be avoided to reduce the risk of infection
Increased risk of preterm labour
When is a cone biopsy done?
As a treatment for CIN and very early-stage cervical cancer under general anaesthetic
How is a cone biopsy done?
Surgeon removes a cone-shaped piece of the cervix using a scalpel - sent to histology to assess for malignancy
What are the main risks of a cone biopsy?
- Pain
- Bleeding
- Infection
- Scar formation with stenonsis of the cervix
- Increased risk of miscarriage and premature labour
What is the international federation of Gynaecology and Obstetrics (FIGO) staging system for 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 is the usual treatment for cervical intraepithelial neoplasia and early-stage 1A cervical cancer?
LLETZ or cone biopsy
What is the treatment for:
Stage 1B – 2A
Stage 2B – 4A
Stage 4B cervical cancer?
Stage 1B – 2A: Radical hysterectomy and removal of local lymph nodes with chemotherapy and radiotherapy
Stage 2B – 4A: Chemotherapy and radiotherapy
Stage 4B: Management may involve a combination of surgery, radiotherapy, chemotherapy and palliative care
What is the range of 5 year survival depending on stage of cervical cancer?
98% with stage 1A
15% with stage 4
When is pelvic exenteration used?
Advanced cervical cancer
What is pelvic extenteration?
Operation to remove most or all of the pelvic organs, including the vagina, cervix, uterus, fallopian tubes, ovaries, bladder and rectum (vast operation and has significant implcations on the quality of life)
What chemotherapy agent is used in the treatment of metastatic or recurrent cervical cancer?
Bevacizumab (avastin) a monoclonal antibody
What is the MOA of bevacizumab?
Targets vascular endothelial growth factor A (VEGF-A) which is responsible for the development of new blood vessels
What else is Bevacizumab used for?
Wet age-related macular degeneration - where it is injected directly into the patients eye to stop new blood vessels forming on the retina
What is the current NHS vaccine against HPV?
Gardasil (protects against stains 6, 11, 16 and 18)
Which strains of HPV cause genital warts?
6 and 11
Which strains of HPV cause cervical cancer?
16, 18 and 33
What helps when counselling parents for HPV vaccination?
It needs to be given before their child is sexually active and it protects them from cervical cancer and genital warts.
HPV is very common and infection is the number one risk factor for cervical cancer.
What is endometrial cancer?
Cancer of the endometrium, the lining of the uterus
What type of cancer are most endometiral cancers?
Adenocarcinoma
What stimulates the growth of endometrial cancer?
Oestrogen
What is the most likely diagnosis of a woman with postmenopausal bleeding?
Endometrial cancer
What is endometrial hyperplasia?
Precancerous condition involving thickening of the endometrium
What % of endometrial hyperplasias go on to become endometrial cancer?
5%
What are the two types of endometrial hyperplasias?
- Hyperplasia without atypia
- Atypical hyperplasia
How is endometrial hyperplasia treated?
By a specialist using progestogens with:
- Intrauterine system (e.g. Mirena coil)
- Continuous oral progestogens (e.g. medroxyprogesterone or levonorgestrel)
What is unopposed oestrogen?
Oestrogen without progesterone
What exposure puts a patient at risk of endometrial cancer?
Exposure to unopposed oestrogen
What are some causes of increased unopposed oestrogen?
- Increased age
- Earlier onset of mensturation
- Late menopause
- Oestrogen only HRT
- No or fewer pregnancies
- Obesity
- Polycystic ovarian syndrome
- Tamoxifen
How does polycystic ovarian syndrome lead to increased exposure to oestrogen?
Lack of ovulation
How does PCOS cause the endometrium to have more exposure to unopposed oestrogen?
What can be given to women with PCOS for endometrial protection
Combined contraceptive pill
Intrauterine system
Cyclical progesterones
Why is obesity a risk factor for endometrial cancer?
Adipose tissue is a source of oestrogen
What is the primary source of oestrogen in post menopausal women?
Adipose tissue
How does adipose tissue cause increases in oestrogen?
Contains aromatase which is an enzyme which converts androgens such as testosterone into oestrogen
Where are androgens mainly produced?
How does tamoxifen increase the amount of unopposed oestrogen?
Anti-oestrogenic effect on breast tissue but an oestrogenic effect on the endometrium
What are some risk factors for endometrial cancer which are not related to unopposed oestrogen?
Type 2 diabetes
Hereditary nonpolyposis colorectal cancer or lynch syndrome
How may type 2 diabetes increase the risk of endometrial cacner?
Increased production of insulin which stimulates the endometrial cells, causing hyperplasia and possibly cancer
What is the relationship between PCOS and insulin?
PCOS is associated with insulin resistance and increased insulin production
What are some protective factors for endometrial cancer?
COCP
Mirena coil
Increased pregnancies
Cigarette smoking
How is smoking protective against endometrial cancer?
Anti-oestrogenic
What oestrogen dependent cancer is smoking not protective against?
Breast cancer
How does smoking have an antioestrogenic effect?
- Oestrogen may be metabolised differently in smokers
- Smokers tend to be leaner and so have less adipose tissue and aromatase enzyme
- Smoking destroys oocytes (eggs) resulting in an earlier menopause
What is the main presenting symptom for endometrial cancer?
Post-menopausal bleeding
How else may endometrial cancer present?
Postcoital bleeding
Intermenstrual bleeding
Unusually heavy menstrual bleeding
Abnormal vaginal discharge
Haematuria
Anaemia
Raised platelet count
When is a 2WW referral needed for suspected endometrial cancer?
Postmenopausal bleeding (more than 12 months since last menstrual period)
When is a transvaginal ultrasound required for women over 55 years old?
Unexplained vaginal discharge
Visible haematuria (plus raised platelets, anaemia or elevated glucose levels)
What are the three investigations for diagnosing and excluding endometrial cancer?
What is a pipelle biopsy?
Speculum examination with a thin tube inserted into the uterus through the cervix - tube fills with a sample of endometrial tissue that can be examined for endometrial hyperplasia or cancer
Why is a pipelle biopsy better than a hysteroscopy for excluding cancer in lower-risk women?
It’s a quicker and less invasive alternative to hysteroscopy
What investigations are sufficient to rule out endometrial cancer and dischage a patient?
- Normal transvaginal ultrasound (endometrial thickness < 4mm)
- Normal pipelle biopsy
What is the FIGO staging for 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 the usual treatment for stage 1 and 2 endometrial cancer?
Total abdominal hysterectomy with bilateral salpingo-oophorectomy (TAH and BSO - removal of cervix, uterus and adnexa)
What are the other treatments for endometrial cancer?
Radical hysterectomy (also removing the pelvic lymph nodes, surrounding tussue and top of the vagina)
Radiotherapy
Chemotherapy
Progesterone for hormonal treatment to slow the progression of the cancer
Why does ovarian cancer often present late?
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 are some different types of ovarian cancers?
What is the most common type of ovarian cancer? And some subsets?
Epithelial cell tumours
- Serous tumours (the most common)
- Endometrioid carcinoma
- Clear cell tumour
- Mucinous tumour
- Undifferentiated tumour
Are dermoid cysts / germ cell tumours benign or malignant?
Benign
What kind of tumours are dermoid cysts and germ cell tumours?
Teratomas (they come from germ cells)
What do teratomas contain?
Various tissue types such as skin, teeth, hair and bone
What are germ cell tumours associated with?
Ovarian torsion
What tumour markers may be raised in germ cell tumours?
Alpha-fetoprotein
Human chorionic gonadotrophin
Are sex cord-stromal tumours cancerous?
Can be benign or malignant
What are some types of sex cord-stromal tumours?
Sertoli-leydig cell tumours
Granulosa cell tumours
What is a krukenberg tumour?
Metastasis in the ovary, usually from a gastrointestinal tract cancer particularily the stomach
How do Krukenberg tumours appear on histology?
“Signet ring” cells on histology
What are some risk factors for ovarian cancer?
Age (peaks at 60)
BRCA1 and BRCA2 genes (consider the family history)
Increased number of ovulations
Obesity
Smoking
Recurrent use of clomifene
What are the factors which increase the number of ovulations (and thus the risk of ovarian cancer)?
- Early onset of periods
- Late menopause
- No pregnancies
What are some factors which are protective against ovarian cancer?
- Combined contraceptive pill
- Breastfeeding
- Pregnancy
How can ovarian cancer present?
Abdominal bloating
Early satiety (feeling full after eating)
Loss of appetite
Pelvic pain
Urinary symptoms (frequency / urgency)
Weight loss
Abdominal or pelvic mass
Ascites
(have a low threshold for referring older women)
Why does hip/groin pain occur in ovarian cancer?
Due to compression on the obturator nerve (as it passes along the inside of the pelvis, lateral to the ovaries)
When should a 2WW referral be made for suspected ovarian cancer?
- Ascites
- Pelvic mass (unless clearly due to fibroids)
- Abdo mass
What symptoms should prompt further investigations for ovarian cancer (starting with CA125)?
Women older than 50 presenting with:
New symptoms of IBS / change in bowel habit
Abdominal bloating
Early satiety
Pelvic pain
Urinary frequency or urgency
Weight loss
What are the inital investigations for ovarian cancer in primary or secondary care?
CA125 blood test (>35 is significant)
Pelvic ultrasound
What is the risk of malignancy index (RMI) calculating?
Risk of an ovarian mass being malignant
What is the RMI based on?
Menopausal status
Ultrasound findings
CA125 level
What are some other further investigations in secondary care to include?
CT scan to establish the diagnosis and stage cancer
HIstology (tissue sample) using a CT guided biopsy, laparoscopy or laparotomy
Paracentesis (ascitic tap) - assesses ascitic fluid for cancer cells
What tumour markers are required for a woman under 40 with a complex ovarian mass?
α-FP
hCG
What cancer is CA125 a marker for?
Epithelial cell ovarian cancer
What are the non-malignant causes of a raised CA125?
- Endometriosis
- Fibroids
- Adenomyosis
- Pelvic infection
- Liver disease
- Pregnancy
What are the stages of the FIGO system used for ovarian cancer?
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)
How is ovarian cancer managed?
Specialist gynarcology oncology MDT usually involving a combination of surgery and chemotherapy
Is vulval cancer common?
Rare (compared with other gynarcological cancers)
What is the most common type of vulval cancers?
90% are squamous cell carcinoma (less commonly malignant melanoma)
What are some risk factors for vulval cancers?
- Advanced age (over 75)
- Immunosuppression
- HPV (human papillomavirus) infection
- Lichen sclerosus
What percent of women with lichen sclerosus get vulval cancer?
5%
What is vulval intraepithelial neoplasia?
Premalignant condition affecting the squamous epithelium of the skin preceding vulval cancer
What is a high grade squamous intraepithelial lesion?
Type of VIN associated with HPV infection that typically occurs in younger women aged 35-50 years
What is differentiated VIN?
Alternative type of VIN associated with lichen sclerosus, typically occuring in older women (aged 50-60 years old)
How is VIN diagnosed?
A biopsy
What are the treatment options for VIN?
Watch and wait with close follow up
Wide local excision (surgery) to remove the lesions
Imiquimod cream
Laser ablation
How may vulval cancer present?
Symptoms of:
Vulval lump
Ulceration
Bleeding
Pain
Itching
Lymphadenopathy in the groin
Where does vulval cancer commonly affect?
Labia majora
How to establish diagnosis of vulval cancer and stage?
Biopsy of the lesion
Sentinel node biopsy to demonstate lymph node spread
Further imaging for staging (CT abdo and pelvis)
What staging system is used for vulval cancer?
FIGO
What is the management of vulval cancer?
Wide local excision to remove the cancer
Groin lymph node dissection
Chemotherapy
Radiotherapy
