womens repro Flashcards
Genital human papillomaviruses (HPVs)
- role of early genes?
- role of late genes?
- common ‘low risk’ strains? 2
- common ‘high risk’ strains? 2
early genes:
- subvert host cell’s replicating apparatus to benefit virus
late genes:
- package virons so they can be expelled to infect other cells
low risk:
- cause benign genital warts (if anything)
- 6 + 11
- “6:11am is an annoying time to wake in the morning but not catastrophic”
high risk:
- can lead to cervical cancer
- 16 + 18
- “average age for people to loose thei virginity is between 16-18, promiscuous sex increases change of cervical cancer”
nb types 16 + 18 are included in HPV vaccine, but only cause 70% of cervical cancers so can still get cervical cancer if you’ve been vaccinated!
what are the 2 HPV vaccines given in the UK, what is each effective against + which is used now?
cervarix
- against 16 + 18 ONLY
- “just protects against CERVical cancer, not warts too”
- initially given from 2008 (incl catch-up)
gardasil
- against 6, 11, 16 + 18
- “GuARDs against both cancer + warts”
- used from 2012 onwards
nb types 16 + 18 are included in HPV vaccine, but only cause 70% of cervical cancers so can still get cervical cancer if you’ve been vaccinated!
what is the mechanism by which ‘high risk’ HPVs increase the risk of cancer?
‘high risk’ HPVs intergrate their DNA into host’s chromosome
as a byproduct of this process…
- E6 (binds to + inactivates P53)
- E7 (binds to RB1 gene product)
… are upregulated
P53 triggers apoptosis in response to bad DNA damage
RB1 is a tumour suppressor gene
this all -> increase risk of cancer!
vulval intraepithelial neoplasia:
- what is it?
- 2 different types? (incl cause, who affected)
a precancerous condition which often results in cancer of the vulva if not removed (progression to invasive cancer = 5% in treated women + 85% in untreated women)
classical/warty/baseloid:
- related to HPV infection
- younger women
- graded VIN 1-3
differentiated VIN
- associated with chronic inflammatory skin conditions (eg lichen sclerosus)
- older women
- not graded
- much harder to diagnose + treat
who is invasion of VIN most likely to occur in? 3
- postmenopausal women
- immunocompromised (incl local due to smoking)
- young, postpartum women (ie after give birth)
what is the most common type of vulval cancer?
what is it associated with? 2
what lymph nodes does it tend to spread to first?
what type of lymph node biopsy is done? why?
squamous cell carcinoma
- ‘high risk’ HPV infection
- inflammatory dermatoses (eg lichen sclerosus)
“lichen on your vag”
inguinal lymph nodes
sentinel node biopsy
- find node that stuff drains to first (sentinel)
- do this using radioactive tracer
- biopsy just this lymph node, if negative, likely all will be
- done instead of taking out all lymph nodes which results in lymphoedema in distal limb!
what staging system is normally used for gynae cancers?
FIGO system
not TNM
what two cancers each make up 5% of vulval tumours?
- age affected?
- prognosis?
malignant melanoma:
- 50-60 years
- lymph node/metastasis common -> poor prognosis
Paget’s disease:
- mean age 80
- tend to recur following excision (as doesn’t have well defined edge)
Paget’s disease:
- what is it?
- what is it often mistaken for?
- difference between nipple + vulval?
a type of skin lesion which is: - pruritic - burning - often red/inflammed it is a potentially pre-cancerous condition
often confused for eczema
- ALWAY biopsy ‘ezcema’ around nipple or vulva to check for paget’s as treating it with steroid cream (standard treatment for ezcema) could lead it to become cancerous
nipple (mammary) paget’s almost always has breast cancer under it whereas vulval (extra-mammary) doesn’t tend to and only rarely becomes adenocarcinoma
what changes to the epithelium of the cervix occur during a woman’s life?
where are cervical smear tests taken from? why?
columnar epithelium is in vagina, squamous epithelium is on skin
before puberty squamocolumnar junction is quite internal but then metaplasia occurs during menarche, produces a ‘transformation zone’ where squamous turns to columnar
after a woman’s menopause the transformation zone moves more internally into the vagina as more squamous cells are produced more externally
the transformation zone, as this is where dysplasia (and then cancer) almost always develops from
nb since the transformation zone in older women goes more internally, the smear test is more likely to miss it as it doesn’t go deep enough, so lots of false negatives in older women, hence why cervical smear less useful for older women
cervical intraepithelial neoplasia (CIN)
- what is it?
- grades?
- treatment for each grade?
a potentially premalignant dysplasia of cervical cells (normally in transformation zone)
CIN 1, 2 + 3
- indicate increasing dysplasia and likelihood of progression to invasion
CIN 1 - watch + wait (60% goes away)
CIN 2 or 3 - excision
cervical screening programme:
- age of first invitation?
- frequancy?
why no screening below this age of first invitation?
25
every 3 years until you’re 50
then every 5 years until your 65
rarely after 65, unless had abnormal tests
nb slightly different in different parts of UK
- high HPV carriage rate
- reactive changes
… mean this confuses results and there is a high false postive rate - unnecessary procedures to remove things have obstetric consequences
what is a colposcopy?
what is LLETZ?
examination of the cervix with a low powered stereoscopic microscope
cervix often painted with acetic acid to highlight potentially abnormal epithelium which can then be resected using a diathermy loop
this resection is called a large loop excision of the transformation zone (LLETZ) and is then studied by histopathologists
- nb side effect is large risk of miscarriages to future pregnancies
what is the algorithm followed in the case of abnormal smear tests?
smear tests test for abnormal cytology (ie dysplasia) AND HPV infection
if there is low level dysplasia WITHOUT HPV infection -> normal recall
if there is low level dysplasia WITH HPV infection -> refer for colposcopy
if there is high level dysplasia (with or without HPV infection) -> refer for colposcopy
risk factors for cervical squamous cell carcinoma:
- biggest?
- 2nd biggest?
- others? 6
high risk HPV
smoking (2nd) - causes local immunosuppression
- multiple sexual partners
- male partner with multiple partners
- young age at first intercourse
- high parity (given birth lots)
- low socioeconomic group
- immunosuppression
cervical adenocarcinoma
- cause?
- precursor?
- treatment?
- prognosis? why?
related to high risk HPV infection
cervical glandular intraepithelial neoplasia (CGIN)
treated same as squamous carcinoma or cervix (presention + spread are the same too)
stage for stage worse prognosis than squamous
- due to radiotherapy resistance
nb often found further up the cervix and so may produce false negatives on smear tests
cervical carcinoma:
- treatment?
- lymph nodes commonly metastasise to?
depends on FIGO stage
- from just LLETZ to varying levels of chemo + radiotherapy
nb try to avoid chemo/radiotherapy in young woemn as reduces fertility
pelvic + para-aortic
endometriosis:
- what is it?
- symptoms? 6
- diagnosis?
- treatment?
ectopic endometrial tissue (various theories as to aetiology) -> bleeding into tissue -> fribrosis -> pain
- dysmenorrhoea (painful periods) - main one!
- dyspareunia (painful sex)
- pelvic pain
- subfertility (if on ovaries)
- pain on passing stool
- dysuria
… depends where ectopic tissue is!
nb mismatch between how much endometriosis is present and severity of symptoms (can be asymptomatic)
laparoscopy used to diagnose
medical: - combined oral contraceptive - GnRH agonists/antagonists - progesterone antagonists surgical: - ablation - hysterectomy
endometritis:
- what is it?
- causes? 4
- symptoms? 5
- diagnosis? 2
- treatment? 3
- histological difference between acute + chronic?
inflammation of the endometrium
- pelvic inflammatory disease (caused by STIs like chlamydia/gonnorhoea)
- retained gestational tissue
- endometrial TB
- IUCD infection
- abdominal/pelvic pain
- pyrexia
- discharge
- dysuria
- abnormal vahinal bleeding
- biochemistry/microbiology
- ultrasound
- analgesia
- Abx
- remove cause (eg coil or retained tissue)
acute = neutrophil dominant chronic = lymphocyte/plasma cell dominant
endometrial polyps:
- symptoms? 3
- diagnosis? 2
- treatment?
- prognosis?
often asymptomatic
- intermenstrual/post-menopausal bleeding
- menorrhagia
- dysmenorrhoea
- ultrasound
- hysteroscopy
depends (medical or surgical options available)
< 1% are malignant
- but tend to remove anyway, just in case
leiomyoma (uterine fibroids):
- what is it?
- risk factors? 5
- symptoms? 4
- prognosis?
benign tumours of smooth muscle of uterus
- genetics
- nulliparity (never had a baby)
- obesity
- polycystic ovary syndorme
- hypertension
often asymptomatic
- menometorrhagia (heavy periods w increased frequency)
- iron deficient anaemia (dt loss of blood)
- subfertility/preg problems (as can thin overlying endometrium)
- heaviness or pressure in lower abdo (eg bloating feeling)
good prognosis (only very rarely -> leiomyosarcoma) - leiomyosarcomas normally develop de novo (ie not from fibroids)
endometrial hyperplasia:
- what is it? mechanism?
- risk factors? 6
- types? 4
excessive endometrial proliferation
- due to a high level of unopposed oestrogen (ie RELATIVELY lower levels of progesterone, which antagtonises oestrogen)
anything that increases oestrogen:
- obesity (^oestrogen)
- exogenous oestrogen
- polycystic ovary syndrome
- oestrogen producing tumours
- tamoxifen (blocks E receptors in breast cancer, stimulates them in endometrium)
- HNPCC
- simple non-atypical
- simple atypical
- complex non-typical
- complex atypical
nb atypia matters more than simple/complex
nb hard to tell difference histoligically between non-atypical and normal proliferation during parts of menstural cycle
endometrial hyperplasia:
- symptoms? 3
- diagnosis? 2
- treatment? 3
- prognosis?
abnormal bleeding
- inter-menstural bleeding
- post-coital bleeding (bleeding after sex)
- post-menopausal bleeding
- ultrasound
- hysteroscopy +/- biopsy
medical (if patient young + wants kids): - IUS - progesterone surgical (if wants no more kids): - hysterectomy
often develops into endometrial adenocarcinoma
endometrial adenocarcinoma:
- symptoms? 4
- stagingsystem used?
- treatment?
abnormal bleeding: - post-menopausal - inter-menstural - post-coital pain (if late stage)
FIGO (1-4)
medical: - progesterone surgery - hysterectomy adjuvent therapy - chemo - radio`
nb this is most common kind of endometrial MALIGNANT neoplasm
polycystic ovary syndrome:
- what is it?
- levels of LH and FSH?
- risk factors? 3
- diagnostic criteria?
a syndrome due to high androgen (eg testosterone) levels in women
- low FSH
- high LH
- family history
- obesity
- diabetes/metabolic syndrome
Rotterdam criteria: have 2/3 of:
- hyperandrogenism
- polycystic ovaries (on ultrasound)
- irregular periods (>35 days apart)
polycystic ovary syndrome:
- symptoms? 6
- treatment?
- can lead to? 2
nb a lot are asymptomatic
- irregular periods (or none)
- difficulty concieving
- excessive hair growth
- weight gain
- thinning hair + hair loss from the head
- oily skin/acne
lifestyle: - weight loss (has huge effect) medical: - metformin - oral contraceptive pill - clomiphene (-> upregulation of FSH) surgical: - ovarian drilling
- infertility
- endometrial hyperplasia/adenocarcinoma
what are the two types of (female) gonadal failure? (both names!)
- symptoms? 2
- investigations? 2
- treatment? 2
HYPERgonadotrophic hyponadism (primary hypogonadism)
- primary failure of gonads
- high GnRH
HYPOgonadotrophic hypogonadism (secondary hypogonadism)
- hypothalamic/pituatory failure -> gonad failure
- low/no GnRH
- amenorrhoea/absent menarche
- delayed puberty
- hormonal profiling
- karyotyping
difficult to treat:
- address cause
- hormone replacement therapy
Hypergonadotrophic hypogonadism:
- congenital causes? 2
- acquired causes? 4
aka primary hypogonadism
congenital:
- turner syndrome (XO)
- klinefelter’s syndrome (XXY)
acquired:
- infection
- surgery
- chemo-radiotherapy
- toxins/drugs
hypogonadotrophic hypogonadism:
- acquired causes? 3
aka secondary hypogonadism
Sheehan syndrome:
- lots of blood loss (eg in complicated preg) -> hypovolemia -> ischaemic damage to pituatory gland -> secondary gonadal failure
brain injury
- eg one which ->severing of pituatory stalk so hypothalamus can’t signal to pituatory
pituatory tumours
3 broad types of ovarian tumours?
which is, by far. most common?
surface epithelial tumours
- 90% (most common)
- nb they think these may actually originate in fallopian tube…
sex-cord stromal tumours (supportive cells)
germ cell tumours (‘the egg’)
nb epithelial tumours are always more common than non-epithelial ones as the cells are reproducing faster
germ cell tumours:
- germinomatous? 1
- non-germinomatous? 3
say malignant/benign + whether chemosensittive for each
dysgerminomas
- germinomatous
- malignant
- chemosensitive
teratomas
- non-germinomatous
- almost always benign in women
- often malignant in men
yolk sac tumours
- non-germinomatous
- malignant
- chemosensitive
choriocarcinomas (‘trying to be’ a placenta)
- non-germinomatous
- malignant
- often unresponsive to chemo
sex cord stromal tumours:
- incidence?
- benign/malignant?
- prognosis?
rare
almost always benign
however often produce androgens or oestrogen -> hormonal problems
