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Gynae > Gynae- cervix > Flashcards

Gynae- cervix Flashcards

1
Q

Risk factors for cervical cancer

A
  • HPV infection (>90% cervical ca cases)
  • Immunocompromised (HIV/AIDS, transplant)
  • Smoking
  • Hx STDS
  • Young age at first intercourse
  • multiple sexual partners
    (those 3 above surrogates for HPV exposure)
  • low SES
    -Diethylstilbestrol (DES) exposure in utero (assoc with clear cell adenocarcinoma of cervix/vagina)
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2
Q

What are the high risk HPV strains?

A

16, 18 (highest risk of carcinogenesis) (account for 65-70% of cases).

Other cancer causing strains are 31,33,45,52,58

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3
Q

What is the epithelium of endocervix and ectocervix?

A

Endo- columnar
Ecto- squamous

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4
Q

What is the most common site of carcinogenesis?

A

Squamo-columnar junction located at external os

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5
Q

What is the natural hx of cervical cancer?

A

Local invasion

Lymph node spread

Mets: Lungs, supraclav LNs (via thoracic duct), bones, liver

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6
Q

What are the histological subtypes of cervical cancer?

A
  • SCC (70-75%)
  • Adenocarcinoma (20-25%)
  • Clear cell adenoCa
  • small cell
  • neuroendocrine
  • sarcoma (RMS)
  • melanoma
  • Adenoid cystic carcinoma
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7
Q

How does adenoCa classically present and is it better or worse than SCC?

A
  • large tumours in young women
  • “barrel cervix”
  • arise in endocervix
  • higher risk of local failure
  • stage for stage does worse than SCC
  • cervical smear less sensitive for this histology
  • less related to HPV than SCC, so as the number of HPV mediated SCCs in young women decrease, proportionately more adenoCas are seen.
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8
Q

Current cervical screening in NZ

A

Cervical smears 3yearly ages 20-69.
- repeat smear after 1 year if 1st smear or more than 5 years from last

Changing to HPV self swabs July 2023
- more effective at detecting women at high risk for developing Cervical ca
-

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9
Q

Clinical symptoms of cervical cancer?

A
  • Asymptomatic, detected on screening
  • abnormal vaginal discharge
  • post-coital bleeding
  • dyspaerunia
  • pelvic pain
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10
Q

Important history and physical exam work up for cervical ca?

A

History:
- Detailed gynae hx
- sexual hx
- fertility wishes
- possible pregnancy

Exam:
- abdominal and pelvis exam with attention to inferior extension into vagina, lateral extension into parametric, posterior extension into uterosacral ligament or rectum
- Supraclavicular LN
- Inguinal LN

Smoking cessation counselling

EUA:
- cystoscopy and proctoscopy for advanced disease or if bladder or rectal extension is suspected

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11
Q

Lab work up for cervical cancer?

A

FBC (Hb prognostic indicator)

UEs (Cr ^&raquo_space; hydronephrosis due to LA dz)

LFTs (chemo fitness)
HepB and C (chemo fitness)
HIV

Pregnancy test

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12
Q

Imaging work up for cervical cancer?

A

CT and FDG-PET for nodal staging

Pelvic MRI (better images for delineation of tumour extension into surrounding soft tissue)

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13
Q

Epidemiology for cervical cancer?

A
  • Females
  • Median age 49 but wide range of ages seen (20s-80s)
  • 6/100,000 pa in NZ
  • Incidence decreasing as screening increases detection of precancerous (CIN) and due to implementation of HPV vaccine.
  • Increased incidence in developing nations
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14
Q

Lymphatic drainage of cervix?

A

pre sacral and obturator

Internal and external iliac&raquo_space;> common iliac&raquo_space;> para-aortic&raquo_space;> Supraclav fossa

Inguinal if lower 1/3 vagina involved.

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15
Q

Cervix- high yield anatomy

A
  • cylindrical lower part of uterus
  • endocervical canal runs through it connecting uterus to vagina
  • distal part of cervix (ectocervix) projects into the vagina
  • Broad and cardinal ligaments attach Ut and Cx to pelvic side wall
  • Low uterus attached to sacrum by uterosacral ligament.
  • lymphatic drainage of cervix is through these ligaments to LN stations
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16
Q

Prognostic factors

(Patient)

A

Patient:
- Hb <100g/L
- increased age

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17
Q

Macro features of SCC cervix

A

Ulcerated, exophytic, friable, red, tan, grey mass

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18
Q

Macro features of Adeno cervix

A

Barrel shaped cervix located in endocervix

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19
Q

Micro features of SCC cervix

A

Tumor cells infiltrating as irregular anastomosing nests or single cells within desmoplastic or inflammatory stroma

squamous features
- keratin pearls
- intracellular bridges

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20
Q

micro features of Adeno cervix

A

Stromal infiltration in the form of:
- Marked glandular confluence with cribriform or microacinar architecture
- Irregularly shaped, angulated or fragmented glands with an adjacent desmoplastic stromal reaction
- Tumor cell clusters or individual cells
- Lymphovascular space invasion
- Increased number of glands with loss of a lobular arrangement and glandular density exceeding that of the normal cervix

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21
Q

Variants of SCC cervix

A

Keratinising
Non-keratinising
Papillary
Baseloid (palisading, aggressive)
Warty
Verrucous
Lymphoepithelial like
Spindled/sarcomatoid
Squamotransitional

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22
Q

Molecular/cytogenetics of Cervical ca

A

TP53 mutations in 16%
KRAS mutations low frequency
PIK3CA mutations most frequent (37%)

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23
Q

Variants of Adeno cervical cancer

A

usual type - 80%, mucin depleted epithelium
Mucinous
Endometroid (ddx endometrial ca)
Clear cell
Gastric type adenoma
Serious papillary (need to check)
Mesonephric

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24
Q

Immunohistochemistry for cervical SCC

A

Positive:
Panycytokeratin
CK5/6
EMA
p63
p40
p16
CK7

Negative:
CK20
Inhibit, MEL-CAM, HPL
Napsin-A

25
Q

Is grade prognostic in SCC cervix?

A

No

26
Q

Immunohistochemistry in cervical Aden

A

Positive:
p16
mCEA
CK7

Negative:
ER,PR
CK20
p63
CDX2

27
Q

Prognostic factors (Tumour)

A

Tumour:
- Tumour size (>4cm worse)
- Increased stage
- LN involvement
- LVSI

28
Q

Prognostic factors (treatment)

A

Treatment:
- prolonged OTT >56 days
- inadequate cover of HR-CTV <85Gy
- persistent PET uptake after treatment

29
Q

What doses are used in EMBRACE II protocol?
EBRT and BT contributions

A

EBRT:
45Gy/25# to whole ITV

Inside true pelvis involved nodes boosted to 55Gy/25#
(quivalent to 56 Gy EQD2 EBRT + 3-4 Gy EQD2 from BT which results in a total dose of ~60 Gy EQD2.)

Outside true pelvis nodes boosted to 57.5Gy/25#
(This schedule is equivalent to ~59 Gy EQD2 and BT dose contribution is negligible.)

HDR Brachy boost:

30
Q

What stages proceed to surgery?

A

Stage IA1-IB2 and IIA

31
Q

What is FIGO 2018 IA

A

IA- confined to cervix and microscopic lesion

32
Q

What is FIGO 2018 Stage IB

A

confined to cervix and >5mm DOI

33
Q

What is FIGO 2018 stage II

IIA vs IIB?

A

Extension beyond uterus but not to side wall or lower third of vagina

A- no parametrical invasion but size differs
A1 less than or equal to 4cm
A2 greater than 4cm

B Parametrial invasion

34
Q

What is FIGO 2018 stage IIIA and IIIB?

A

IIIA- involves lower third of vagina

IIIb- extends to pelvic side wall or causes hydronephrosis/kidney impairment

35
Q

What is FIGO 2018 Stage IVA

A

invasion of bladder/rectum/extends beyond true pelvis

36
Q

What is FIGO 2018 stage IIIC1

A

pelvic LN mets

37
Q

What is FIGO 2018 stage IIIC2

A

Para-aortic lymph nodes (with or without pelvic)

38
Q

What is FIGO 2018 stage IVb

A

Distant mets

39
Q

What did the INTERLACE trial test and what did it show?

A

Induction chemo (carboplatin and paclitaxel) plus chemoradiation vs chemoRT alone for locally advanced cervical cancer.

OS and PFS benefit in induction chemo arm

40
Q

What fertility preserving options are there?

A

Trachelectomy and conisation

41
Q

Who are fertility sparing procedures appropriate for?

A

Conisation- Stage IA1/IA2
Trachelectomy- IB1

42
Q

What stages are appropriate for chemoradiation+brachytherapy?

A

Stage IB3 (confined to cervix, >5mm DOI and greater or equal to 4cm)

43
Q

What is the management of Stage IB-IIA cervical cancer?

A

Both surgery or RT are options.
Trimodality treatment should be avoided

44
Q

What is the evidence to support management of stage B- IIA cervical cancer?

A

London Italian trial (Lancet 1997)
Phase III RCT
Radical hysterectomy or radical RT
Identical OS and DFS in surgery and RT groups
recurrence rate 25% in both
severe toxicity 28% in surgery vs 12% RT
Adenocarcinoma did better with surgery (better OS)

45
Q

What are the three routes of treatment options for curative intent cervical cancer?

A
  1. Fertility preserving surgery
  2. Radical hysterectomy +PLND (+- adjuvant RT or CHT)
  3. Definitive chemoradiotherapy + Brachytherapy
46
Q

Describe risk factors for cervical adenocarcinoma (exam Q)

A

HPV infection
OCP use
HRT use

47
Q

Describe risk factors for cervical SCC (exam Q)

A

HPV infection
Sexual history
smoking
immunosuppression

48
Q

Describe the epidemiology of cervical adenocarcinoma (exam Q)

A

Less common than SCC (15% of cervical cancer)
usually arise from the endo cervix

49
Q

Describe the epidemiology of cervical SCC

A

Most common type of cervical ca (85%)
Usually arise from echo-cervix

50
Q

Using immunohistochemistry, how to differentiate between adenocarcinoma of the cervix (endocervical/ NOS) and well-differentiated endometrial carcinoma (Type 1 endometroid carcinoma (exam Q)

A

Endo-cervix adenoca:
p16+ (in 95% of cases),
ER/PR- (or weak)
Others: CEA + (100% of cases), CK7+

Endometrial adenocarcinoma:
Tumour usually in continuity with an endometrial primary tumour Usually myometrial invasion
ER/PR+
p16-, HPV DNA-
Others: CEA -, vimentin +

51
Q

Describe the 4 major steps in the development of an HPV related cervical cancer? (exam Q)

A

HPV infection
(50% clear infection approx 8 months, 90% in 2 years)

Persistence
(Due to failure to clear virus, allows integration of viral DNA into host cell genome)

Pre-cancerous lesion
(development of high grade squamous intra-epithelial lesion (HSIL)

Invasion
(malignant transformation into cancer)

52
Q

Give evidence for use of intracavitary BT boost in for definitive chemoRT in cervical cancer

A
  • Lanciano et al: analysed pre-treatment and treatment factors which improved outcomes in cervical cancer and found the only treatment factor which impacted pelvic control rates was the use of intra-cavitary brachytherapy. There was a higher incidence of local failure if EBRT alone is used.
  • Han et al: Review of SEER database (7359 patients treated between 1988-2009, for stage Ib2-IVA cervical cancer). Cancer specific survival in EBRT + BT vs EBRT alone, at 4 years was 64.3% vs 51.5% (p sig) and OS was 58.2% vs 46.2% (p sig)
  • Robin et al: review of National Cancer DataBase (15194 patients treated for locally advanced cervical cancer between 2004 and 2012). OS was significantly higher in those treated with EBRT and BT compared to EBRT alone (HR 0.554, p sig)
  • Gill et al: review of NCDB (7654 patients with stage IIB-IVA cervical cancer. treated with EBRT + BT boost, or EBRT + IMRT or SBRT boost from 2004-2011). IMRT and SBRT boost resulted in inferior OS (HR 1.86, CI 1..35-2.55, p sig) and increased toxicity when compared to BT boost.
53
Q

What is the evidence for HDR brach vs LDR?

A

2014 Cochrane review by Liu et al. of 4 studies involving 1265 patients compared high dose rate (HDR) brachytherapy with low dose rate (LDR) intracavity brachytherapy (ICBT) in patients with locally advanced cervical cancer (stage I-III).

No diff in any OS/DFS/recurrence outcome between HDR and LDR.

HDR had small increase in bowel toxicity.

HDR significantly more tolerable for patients, more convenient, outpatient treatment, higher accuracy of applicator and source position

54
Q

What is the cisplatin dose for definitive chemo RT?

A

40mg/m2 weekly

55
Q

What does the cervical screening program in NZ consist of?

A

Cervical smear
OR
Vaginal HPV swab test

56
Q

When does cervical screening start in NZ?

A

Starting age 25 for people who have ever been sexually active with cervical or vagina

57
Q

What is the frequency of cervical screening in NZ and age range this falls in?

A

Every five years (or every three years if immune deficient) following a “HPV Not detected” test
aged 25 – 69 years who have ever been sexually active.
Screening is extended to people aged 70 – 74 years who are unscreened or under-screened.

58
Q
A

Gynae (3 decks)

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