3- Reproductive cancer Flashcards
Cervical cancer background
- 3rd most common gynae in England
- More common in developing
- Bimodal age distribution
- Low socioecomic groups
- 50% with cervical cancer have never had a smear
types of cervical cancer
- 2/3 squamous cell carcinoma
- 15% adenocarcinoma
Pre- cancerous condition of cervical cancer
Cervical intraepithelial neoplasia (CIN)
cervical cancer risk factors
- HPV- believed to be exclusively caused by this virus
- Young age at first intercourse
- Multiple partners
- Exposure
- Smoking
- COCP
- Immunosuppression/ HIV
- Non-compliance with cervical screening
- Family history
cervical cancer metastasis
lymph nodes, liver, lungs and bones.
refferal cervical cancer
An individual must be referred to colposcopy and should be seen within 2 weeks of referral (≥93% of cases) if the appearance of the cervix is suspicious or they have symptoms consistent with cervical cancer e.g. intermenstrual (post coital) bleeding
Protective factors for cervical cancers
- HPV vaccine
- Cervical screening compliance
Presentation of cervical cancer
- Post coital bleeding
- PMH
- IMB
- Dyspareunia
- Blood stained vaginal discharge
- If advanced
o Fistulae
o Renal failure
o Nervous root pain
o Lower limb oedema
examination findings for cervical cancer
Ulceration, inflammation, bleeding, visible tumour
Red flags for cervical cancer
- Intermenstrual bleeding including post-coitally
- Changes to vaginal discharge
- Pain during sex
HPV background
- Most women will be infected at some time
- HPV infection is common in late teens and early twenties
- Infection lasts on average 8 months
- Prevalence 5% by age 50
o Immunological clearance of virus
o Reduced opportunities for re-infection - HPV is an accepted necessary (but not sufficient) cause of cervical cancer
- Cervical cancer could be viewed as a rare complication of a common infection
- A vaccine can reasonably be expected to prevent most cases of cervical carcinoma
- Biggest implication is in developing nations
types of HPV
- Oncogenic types: 16 and 18
- Low risk HPV types (warts): 6 and 11
pathophysiology of HPV
HPV (esp subtypes 16 & 18): produce proteins (E6&7) which suppress the products of ‘p53’ tumour suppressor gene in keratinocytes
presentation of HPV
Presentation
* Asymptomatic
* Can be cleared or persist or cause CIN
HPV vaccine
The HPV vaccine is ideally given to girls and boys before they become sexually active. The intention is to prevent them contracting and spreading HPV once they become sexually active. The current NHS vaccine is Gardasil, which protects against strains 6, 11, 16 and 18:
* Strains 6 and 11 cause genital warts
* Strains 16 and 18 cause cervical cancer
Cervical intraepithelial neoplasia (CIN) background
.
- pre- cancerous condition
- 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). The grades are:
- 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.
* Asymptomatic and pre-malignant
* Can regress, persist or progress to cancer
* Best Estimates
* 60% CIN1 regress spontaneously
* 30% of CIN3 progress to invasion over 5-10 years
cervical screening
Smear test
Aim: to pick up precancerous changes
- Starts at 25 years old
- Every 3 years from 25-50
- 5 years from 50-65
- After 65 selected patients only
cervical screening: what happens
- Speculum examination
- Cells collected from cervix (transformation zone) and exfoliated morphology examined
- Samples initially tested for high risk HPV and then Liquid based cytology- UK
Classification / reporting
* Normal
* Inadequate
* Borderline- HPV test
* Mild Dyskaryosis- HPV test
* Moderate Dyskaryosis- coloscopy
* Severe Dyskaryosis- coloscopy
* Possible Invasion
Management of smear results
- 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
investigations for cervical cancer
colposcopy + stains
biopsy
Colposcopy
If HPV positive and abnormal cytology
- Involves inserting a speculum, and using a colposcope to magnify the cervix.
- During stains such as acetic acid and iodine are used to differentiated between abnormal areas
Acetic acid
- Causes abnormal cells to appear white. This appearance is described as acetowhite. This occurs in cells with an increased nuclear to cytoplasmic ratio (more nuclear material), such as cervical intraepithelial neoplasia and cervical cancer cells.
Schiller 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.
types of biopsy
large loop excision of transformational zone (LLETZ)
punch biopsy
cone biopsy for CIN
Large loop excision of transformational zone (LLETZ)
o Under local anaesthetic during colposcopy
o Loop of wire with electrical current (diathermy) used to remove abnormal tissue
o Risk of infection and preterm labour
cone biopsy for CIN
- For treatment of CIN and early cervical cancer
- Surgeon removes a cone-shaped piece of the cervix using a scalpel (pain, bleeding, infection, stenosis of cervix)
cone biopsy for CIN
- For treatment of CIN and early cervical cancer
- Surgeon removes a cone-shaped piece of the cervix using a scalpel (pain, bleeding, infection, stenosis of cervix)
Staging of 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
Management of cervical cancer
Screening very important- management and prognosis depends on the stage of the disease
- Cervical intraepithelial neoplasia and early-stage 1A: LLETZ or cone biopsy
- 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
management of advanced cervical cancer
- Pelvic exenteration: involves removing most or all of the pelvic organs including the vagina, cervix, uterus, fallopian tubes, ovaries, bladder and rectum
- Significant implications on QoL
metastatic cervical cancer management
Metastatic cervical cancer
- Bevacizumab (Avastin): monoclonal antibody
- Targets VEGF-A- reducing development of new blood vessels
prognosis of cervical cancer
- Early detection= better outcomes
- 98% survival with stage 1A, 15% with stage 4
complications of cervical cancer treatment
ovarian cancer
- 2nd commonest gynae cancer
- Incidence rising
- Peak age 70-74
- No pre-malignant stage
o THEREFORE NO SCREENING PROGRAMME
ovarian cancer metastasis
- Peritoneal
- More than 70% of patients with ovarian cancer present after it has spread beyond pelvis
ovarian cancer risk factors
Risk factors
- Obesity
- Nulliparity
- Factors which increase no. of ovulations: Early men/ late men
- Unopposed oestrogen
- Family history
o BRCA1/2
- Endometriosis
- Clomiphene recurrent use
protective factors for ovarian cancer
- COCP
- Pregnancy
- Breastfeeding
- Hysterectomy
- Oophorectomy
- Sterilisation
presentation of ovarian cancer
Presentation- late due to non specific
- Abdominal swelling and ascites
- Pelvic mass
- Pain
- Anorexia
- N and V
- Weight loss
- Vaginal bleeding
- Bowel/urinary symptoms
- Hip/groin pain- mass pressing on obturator nerve
Referral for ovarian cancer
Referral
Refer directly on a 2-week-wait referral if a physical examination reveals:
* Ascites
* Pelvic mass (unless clearly due to fibroids)
* Abdominal mass
ovarian tumours can be
benign
borderline
malignnat
Named according to cell line
most common ovarian tumours
Epithelial
* Serous (most common)
* Mucinous
Germ cells
* Teratoma (dermoid)
Sex cord-stromal tumours
* Benign or malignant
* Arise from connective tissue or sex cords
* E.g. Sertoli-leygid cell tumours and granulosa
Metastasis
* Krukenberg tumour– usually from GI cancer
* Signet ring cells on histology
staging of ovarian cancers
investigations for ovarian cancer
- H and E
- FBC and U&E
- Tumour marker
o CA125 >35 IU/mL
o AFP/LDH/ HCG (<40 years) - Pelvic US
- Pelvic CT
- Paracentesis
- Surgical exploration
- Histopathology
tumour markers for ovarian cancer
o CA125 >35 IU/mL
o AFP/LDH/ HCG (<40 years)
Ca125
This is particularly important in women over 50 years presenting with:
o New symptoms of IBS / change in bowel habit
o Abdominal bloating
o Early satiety
o Pelvic pain
o Urinary frequency or urgency
o Weight loss
causes of raised Ca125
Endometriosis
Fibroids
Adenomyosis
Pelvic infection
Liver disease
Pregnancy
Tumour markers for women under 40 years with complex ovarian mass which could be a germ cell tumour
- Alpha-fetoprotein (α-FP)
- Human chorionic gonadotropin (HCG)
The risk of malignancy index (RMI)
estimates the risk of an ovarian mass being malignant, taking account of three things:
* Menopausal status
* Ultrasound findings
* CA125 level
Staging of ovarian cancer
- CXR
- CT to assess peritoneal, omental and retroperitoneal disease
- Cytology of ascitic tap (paracentesis)
management: eptihelial ovarian cancer
- Surgery + chemotherapy
- Staging laparotomy, TAH PLUS BSO and debulking
- Platinum (Cisplatin, carboplatin) and Taxane (paclitaxel)
- In women of reproductive age, where the tumour is confined to one ovary, oophorectomy only may be considered
Management non-epithelial ovarian cancers:
often occur in young women and can be extremely chemo-sensitive (e.g. germ cell). Often treated with combination of ‘conservative’ surgery and chemo
management of recurrent ovarian cancer
palliative chemotherapy
Endometrial cancer
- Commonest
- Rare before 35 and rare after 80
- More common in postmenopausal
- Common in western world
- Types of endometrial cancer
o Endometrial hyperplasia (pre-cancerous)
o Endometrial carcinoma (adenocarcinoma)
o Sarcoma
endometrial metastases
- Rare at presentation of type 1 cancers
- Intraperitoneal, lung, bone, brain
causes/RF for uterine cancer
- Obesity huge risk- adipose is source of oestrogen
o Primary source of oestrogen in postmenopausal women
o Adipose contain aromatase -> converts androgens such as testosterone into oestrogen
o Unopposed in women not ovulation e.g. PCOS or post-men - T2DM due to increased insulin resistance
- Early menarche/ late meno
- Nulliparity
- PCOS- increased exposure to unopposed oestrogen due to lack of ovulation (due to less likely to ovulate and form CL, which produces progesterone)
- Unopposed oestrogen e.g. tamoxifen
o Anti-oestrogenic in breast, opposite in uterus - Previous breast or ovarian cancer (BRCA ½)
- Endometrial polyps
- Diabetes- due to increased production of insulin in T2
uterine cancer protective factors
Protective
- Continuous combined HRT
- COCP/ mirena
- Multiparety
- Smoking- antiestrogenic- WHATTT
- Coffee/ Tea
- Healthy lifestyle/ PT
Presentation of uterine
- Post menopausal bleeding
- PCB/ intermenstrual bleeding
- Abnormal discharge
- Haematuria
- Anaemia
- Raised platelet count
Referral for uterine cancer
- 2-week wait urgent cancer referral
o Postmenopausal bleeding (>12 months after LMP) - Transvaginal US in women >55 with
o Unexplained vaginal discharge
o Visible haematuria
staging of uterine cancer
Investigations for uterine cancer
One stop postmenopausal bleeding clinic
- H and E
- FBC, UEs, LFT
- Transvaginal ultrasound for endometrial thickness (normal is less than 4mm post-menopause)
- Pipelle biopsy, which is highly sensitive for endometrial cancer making it useful for excluding cancer (quicker and less invasive than hysteroscopy)
o <4mm and normal pipelle biopsy -> discharge patient
- Hysteroscopy with endometrial biopsy
- CT CAP
- MRI pelvis
Transvaginal ultrasound for endometrial thickness
normal is less than 4mm post-menopause
pipelle biopsy
Pipelle biopsy
It involves a speculum examination and inserting a thin tube (pipelle) through the cervix into the uterus. This small tube fills with a sample of endometrial tissue that can be examined for signs of endometrial hyperplasia or cancer. Pipelle biopsy is a quicker and less invasive alternative to hysteroscopy for excluding cancer in lower-risk women.
management of uterine cancer depends on
- Stage
- Age
- Fitness
management of uterine cancer
Preferred treatment: Surgical
Non surgical
- progestagens
- primary radiotherapy
surgical management of uterine cancer
Surgical treatment 80% of patients have primary surgery
- Hysterectomy PLUS bilateral salpingo-oophorectomy, peritoneal washings
- Laparoscopic / Open
**
Adjuvant Radiotherapy if high risk of recurrence**
* External beam
* Brachytherapy
Advanced uterine cancer /inoperable disease/unfit for surgery
- Chemotherapy
- Radiotherapy
- Hormones
- Palliative Care
