Malignant disease of the uterus and lower genital tract Flashcards
Summarise the epidemiology of endometrial cancer.
- Endometrial cancer is the most common gynaecological malignancy in the UK
- 95:100,000
- Mean age 62 years
Name some risk factors for endometrial cancer
- Obesity
- Diabetes
- Nulliparity
- Late menopause, early menarche
- Unopposed oestrogen
- Tamoxifen therapy
- FHx of endometrial- and colorectal cancer
- Lynch syndrome (hereditary non-polyposis colorectal carcinoma)
Name factos that are thought to protect from endometrial cancer
- Hyterectomy
- COCP
- Progestin-based contraceptives
- IUS, Cu-IUD
- Pregnancy
- Smoking
How does endometrial cancer commmonly present?
Compared to ovarian cancer endometrial cancer tends to present at an earlier stage.
Features include:
- The main symptom reported is post menopausal bleeding (PMB), which should be investigated as a red-flag. Before the menopause, abnormal menstrual bleeding (AMB) is a common symptom which can beirregular, heavy or post-coital bleeding.
- Abdominal pain, urinary dysfunction, bowel distrubances (of more advanced)
- Bulky uterus on examination (but usually pelvic examination is normal)
How would you like to investigate endometrial cancer?
Examination:
- Speculum can be normal (exclude atrophy and cervical cancer)
Bloods:
- FBC (anaemia)
Many hospitals have a one-stop clinic dedicated to urgent investigations of women with PMB. The mainstay of diagnoses are TVUSS, hysteroscopy and endometrial biopsy.
- TVUSS allows for a quick and accurate measurement of endometrial thickness. A thickened endometrium is defined as one that measures >4mm indicating endometrial hyperplasia.
- A thickened endometrium requires further evaluation by biopsy and/or hysteroscopy. A biopsy will report the histological subtype and the grade of the tumour. A Pipelle biopsy is the first-line biopsy method, followed by hysteroscopic evaluation and biopsy.
How is endometrial cancer staged?
It is staged using MRI.
The FIGO stages are:
- Confined to uterine body
- Tumour invading cervix
- Local and/or regional spread of tumour
- Tumour invades bladder ± bowel ± distant metastases
What are the two types of endometrial cancer?
There are two types of endometrial adenocarcinomas:
- Type 1 (Endometrioid adenocarcinoma) result from mutations that result in greater levels of oestrogen receptor signalling, and therefore result in tumours that are oestrogen dependent. They also occur from a background of endometrial hyperplasia.
- Type 2 include high-grade serous or clear cell carcinomas and arise from an atrophic endometrium.
Describe the management of endometrial cancer?
- Surgery (1st line)
- Extend depends on grade and stage of disease and patient’s performance status
- Standard is total hysterectomy and bilateral salpingo-oophorectomy. If cervix is involved, perform
- This is usually done abdominally or laparoscopically
- In higher stages, lymph nodes are also dissected
- Adjuvant treatment: (evidence to support this is not too strong)
- Post-operative radiotherapy
- Chemotherapy
- Hormone treatment: (e.g. if not fit for surgery)
- High-dose oral/intra-uterine progestins
- Relapse rates are high with this
Always counsel the woman about freezing eggs.
What is the prognosis for endometrial cancer?
The overall 5-year survival is 80% (but this varies on exact staging).
Describe the screening programme for cervical cancer in the UK.
Starting age 25, all women are invited for 3-yearly screening up to age 50, the 5-yearly up to age 64.
HIV positive woman have yearly screening.
Cervical screening in pregnancy is usually delayed until 3 months post-partum unless missed screening or previous abnormal smears.
Describe the pathway after cervical screening results
- For borderline dyskaryosis or mild dyskaryosis (consistent with CIN I) test for high-risk HPV subtypes (19, 18 and 33):
- A negative HPV is reassuring and the patient goes back to routine recall.
- A positive HPV means the patient is referred for colposcopy.
- For moderate dyskaryosis (consistent with CIN II) or severe dyskaryosis (consistent with CIN III) or suspected invasive cancer the patient should be urgently referred to colposcopy (2 week wait) via the rapid access clinic (RAC) where they are assessed by an MDT.
- Inadequate smears are repeated. The third inadequate smear in a row is referred routinely to colposcopy.
Women who have been treated for CIN I, II or III should be invited 6 months after treatment for ‘test of cure’ repeat cytologyin the community.
How is CIN managed at colposcopy?
Colposcopy is the examination of the magnified cervix using a light source. It is used for both diagnosis and treatment of CIN. Acetic acid or iodine can be used to stain the abnormal cells. The pattern of staining can reveal the extent of CIN.
- If low grade CIN is detected, the patient may be monitored or a biopsy taken. Many low-grade CINs regress spontaneously.
- If high grade CIN is detected, the colposcopist can treat at the same visit (see and treat).
High-grade CIN requires treatment, which in the UK tends to be loop diathermy which is a large loop excision of the transformation zone (LLETZ). This is clinically effective - 95% of patients have negative cytology at 6 months. However, if a large excision, or repeat excision remove a substantial proportion of the cervix, there is an increased risk of midtrimester miscarriage and preterm delivery. Cone biopsy is an alternative for younger patients.
How are women treated at colposcopy followed up?
Women who have been treated for CIN I, II or III should be invited 6 months after treatment for ‘test of cure’ repeat cytology in the community.
What is the underlying aetiology behind cervical cancer?
Cervical cancer is caused by persistent high-risk HPV infection.
High-risk HPV are 16 & 18 (main ones responsible for 70%) and 31, 33 and 45.
Spread is via sexual intercourse.
Around 80% of adults will get infeted during their lifetime, but most clear the infection. When the virus persists, it predisposes the women to premalignant and malignant change.
What HPV strains are associated with genital warts?
Strain 6 & 11
Which part of the cervic is most susceptible to HPV infection?
The transformation zone, aka. squamocolumnar junction. This is where the columnar epithelium of the endocervic transitions into the squamous epithelium of the ectocervix.
This region is most susceptible by metablastic changes induced by HPV.
More notes because I forget:
The endocervix is lined with columnar epithelium whereas the ectocervix is lined with squamous epithelium. Where the two types of epithelium meets is called the squamocolumnar junction (SCJ). In children SCJ lies at the external cervical os, and at puberty it extends outwards onto the ectocervix due to the enlargement of the cervix. It eventually returns back to the external cervical os later in adult life through the process of metaplasia.
The transformation zone (TZ) is the area between the original SCJ and the current SCJwhere metaplasia occurs, turning the columnar epithelium back to squamous epithelium.
When HPV infection persists in certain individuals, it triggers an oncogenic process in the region of the TZ where metaplasia occurs. The TZ is the site of >90% of cervical intraepithelial neoplasias (CIN).
What is cervical intraepithelial neoplasia? Describe its 3 subtypes.
CIN is a pre-cancerous (i.e. not cancer yet!) lesion.
There are 3 subtypes, depending if 1, 2 or 3 thirds of the thickness of the epithelium are made up of abnormal cells. Importantly, the basement membrane is still intact.
How would you investigate and stage suspected cervical cancer?
Suspected cervical cancers should be referred to the rapid access clinic (RAC) where a biopsy is usually done to confirm malignancy, as well as imaging booked for staging:
- MRI of pelvis and CT CAP (chest abdomen pelvis) is used to assess stage of malignancy.
