Cervix

Question 1

Define the range of T1 cervix cancer:

When is definitive EBRT + brachy + non-optional concurrent chemo the only Tx option?

Answer 1

T1 is organ confined. The sub grade is determined by depth of invasion.
a is <5mm DOI (1a1 is <3mm, 1a2 is 3 to 5<mm)
b is 5mm to >4cm (b1 is 5 to 2cm, b2 is 2cm to 4cm, b3 is >4cm).

When there is 4cm or more of invasion the only definitive option is EBRT + brachy + non-optional concurrent chemo. Before that its a shit show of fertility and non fertility sparring options.

Question 2

When is extrafascial hysterectomy a reasonable option?

What is it?

Other options?

Answer 2

For tumors limited to <3mm DOI may be considered as a non-fertility sparring option (modified radical hysterectomy is another non-sparring alternative).

Fertility sparing options:
1) cold knife conization w/3mm margin + PLND IF LVSI
2) Radical trachelectomy + PLND

Brachy alone +/-EBRT

Question 3

At what stage may chemo begin to be considered for Cx cancer?

Answer 3

Stage 1a2 = 3 to up to 5mm DOI
As part of EBRT if high-risk features.

Question 4

A 33yro woman is diagnosed with 4.8mm cervix cancer confined to the cervix.

Because you’ve obviously made some poor life/career choices, list all of the potential options:

Answer 4

T1 a2 (3 to up to 5mm):
Non-fertility options:
1) definitive EBRT + brachy +/- conc chemo
2) Modified radical hysterectomy + PLND

Fertility Sparring:
1) Radical trachelectomy + PLND
2) Cold knife Conization w/3mm margins + PLND

In all surgical cases para-aortic lymph node sampling (PALNS) can be considered.

Question 5

A 33yro woman is diagnosed with 5mm cervix cancer confined to the cervix.

Because you’ve obviously made some poor life/career choices, list all of the potential options:

What if tumour was 4.1cm and still confined to the Cx?

Answer 5

This is T1 b1 (5 to up to 20mm):
For b1 and select b2, there exists a single fertility sparring option:
Trachelectomy w/PLND

Non-fert options:
Radical hysterectomy + PLND
Definitive EBRT + brachytherapy ± concurrent CHT

For T1 B3 disease - the only definitive option is:
Definitive EBRT + brachytherapy + concurrent CHT

Question 6

What is the only exception to the rule that EBRT + brachytherapy + concurrent CHT is the only definitive option beyond FIGO I B2?

Answer 6

Stage IIA may be treated w/radical hysterectomy + PLND

Stage IIA = Extension beyond the cervix BUT not sidewall, or lower 1/3 vagina.

Question 7

HPV infection is associated with ?% of cervical cancer cases.

Which HPV strains confer highest risk of carcinogenesis and account for ?% of cases.

Other cancer-causing strains?

Answer 7

HPV infection is associated with >90% of cervical cancer cases.

HPV 16/18 confer highest risk of carcinogenesis and account for 65% to 70% of cases. HPV 16 may be slightly higher risk than 18.

other cancer-causing strains: 31, 33, 45, 52, 58 (good luck remembering this)

Question 8

Besides HPV, other cervix cancer risk factors include:

Answer 8

Other risk factors include:
smoking,
immunocompromised status (transplant,
AIDS),
history of STDs,
young age at first intercourse,
multiple sexual partners,
multiparity,
low SES,
DES (diethylstilbestrol) exposure in utero (associated with clear cell adenocarcinoma of cervix/vagina).

Question 9

Describe the anatomy of the cervix:

Answer 9

Lower part of uterus, cylindrical in shape. Endocervical canal, lined by columnar epithelium, runs through it and connects uterine cavity to vagina.

Distal part (ectocervix) projects into vagina forming a sulcus (fornix) and is lined by squamous epithelium. Squamo-columnar junction is located at external os and is most common site for carcinogenesis.

Anterior surface not covered by peritoneum and attached to bladder, posterior surface covered by peritoneum forming anterior wall of the pouch of Douglas.

Cardinal ligaments attach cervix to pelvic sidewall (broad attached uterus). Uterosacral ligament attaches low uterus to sacrum. Lymphatics run through these.

Question 10

Histology of the cervix:

Most common site of cancer?

Answer 10

Distal part (ectocervix) projects into vagina and is lined by stratified squamous epithelium. Squamo-columnar junction is located at external os and is most common site for carcinogenesis.

Question 11

Lymphatic drainage of cervix:

Answer 11

Through the ligaments (Cardinal, broad, uterosacral):
1) Broad ligament: obturator, external iliac
2) Cardinal: internal iliac
3) Utero-sacral: Sacral nodes

Also:
common iliac,
Para-aortic

Question 12

Most common sites of Cervix cancer mets:

Answer 12

lungs, supraclavicular LNs (via thoracic duct), bones, and liver.

Question 13

Most common types of cervix cancer:

Answer 13

Squamous cell carcinoma (70%–75%); adenocarcinoma (20%–25%);
adenosquamous (5%).

Question 14

In which age group is adenocarcinoma more common?

How is incidence changing?

Discuss outcomes and screening:

Answer 14

Higher incidence of adenocarcinoma histologies in younger patients.

Adenocarcinoma often presents with larger tumors (“barrel cervix”) with higher risk of local failure.

Incidence is increasing and Pap screening is less sensitive for this histology.

HPV testing may increase sensitivity.

Question 15

Less common malignancies of the cervix

Answer 15

Combined account for 1-5% of cancers:
clear-cell adenocarcinoma,
small cell,
neuroendocrine,
sarcoma (rhabdomyosarcoma in adolescents), melanoma,
adenoid cystic carcinoma.

Question 16

Cervix cancer screening guidelines NZ:

In Australia?

Answer 16

Between 25 and 69 and have ever been sexually active - advise regular three-yearly screening tests.

In 2023: The primary test for cervical screening ( “smear” test) changed to HPV test, with option of self-testing.

In Australia: 25 to 74 years - Cervical Screening every 5 yrs. Since 2017 this has been with HPV testing via speculum (GP) or vaginal (self) swab.

Question 17

It can take ? years for an HPV infection to develop into cervical cancer.

Answer 17

It can take 10 to 15 years for an HPV infection to develop into cervical cancer.

Question 18

Probably not memorable, but interesting:
cumulative incidence rates (CIR) of CIN3+, including cancer, over a 10-year period as follows:

Answer 18

cumulative incidence rates (CIR) of CIN3+, including cancer, over a 10-year period as follows:

17.2% for women with a positive oncogenic HPV test result (type 16)
13.6% for women with a positive oncogenic HPV test result (type 18)
3% for women with a positive oncogenic HPV test result (not 16/18)
0.8% for women in whom oncogenic HPV is not detected.

Question 19

It can take ? years for an HPV infection to develop into cervical cancer.

Answer 19

It can take 10 to 15 years for an HPV infection to develop into cervical cancer.

Question 20

The benefits of cervical cancer screening:

**** Card not finished *****

Answer 20

Need to divide into vaccinated and unvaccinated cohorts:
UnVax:

Question 21

Common presentations of Cx cancer:

Answer 21

Asymptomatic and detected on screening, abnormal vaginal discharge,
post-coital bleeding, dyspareunia, pelvic pain.

Question 22

Initial workup of a patient presenting with a positive cervix screening HPV test:

Answer 22

History:
Symptoms - bleeding, dysparunia, discharge
Risks factors: Previous HPV/lesions/STDs/screening Hx
Fitness for surgery.

Ex:
Abdo+pelvic exam
Manual/bi-manual, DRE, Speculum and smear
Referral for biopsy.

Question 23

Basic epidemiology of cervix cancer:

Answer 23

3rd most common gynae cancer in Australia
Most common world-wide
Median age of Dx = 40

Question 24

Anatomical relation of the cervix to ureters:

Answer 24

Ureters pass 2cm from Cx passing lateral to it, and then anterior to the fornix.

Question 25

Major steps in development of HPV cervical cancer:

(Mechanism of carcinogenesis is another exciting card)

Answer 25

1) Infection: 50% cleared within 8 moths, 90% within 2years - Duration of infection depends on subtype (high-risk longer to )
2) Persistence: Delayed clearance allows integration of viral DNA into host-cell genome
3) Development of high-grade precursor lesion: High grade cervical squamous intra-epithelial lesion (HSIL) - Behavioural factors that increase risk of HSIL: multiparity, long-term OCP use, smoking
4) Invasion and malignant transformation

Question 26

What is the “10% rule” for developing cervix Ca?

Answer 26

10% rule:
10% infection become persistent;
10% persistent will become precursor lesion; 10% precursor lesion will turn into malignant

Question 27

List w/o detail the steps of developing HPV cervix cancer.

Give detail on carcinogenesis:

Answer 27

Infection -> Persistence -> Development of a high-grade precursor lesion -> Invasion and malignant transformation.

Carcinogenesis: Integration of viral DNA to host genome.

HPV invades basal layer of epithelium which acts as a continuous reservoir of HPV DNA.

Inserts into DNA (i.e it is DS-DNA virus), host expresses oncoproteins.

E6 protein binds to and facilitate degradation of p53 protein (p53 is tumour suppressor) → cell progress through G1/S check point with damaged DNA

Question 28

What are the HPV oncogenenes:

How are they expressed?

Answer 28

E5, E6, E7
- Fuck up tumor supressor genes.

HPV invades basal layer of epithelium which acts as a continuous reservoir of HPV DNA.

Inserts into DNA (i.e it is DS-DNA virus), host expresses oncoproteins.

1) E6 protein binds to and facilitate degradation of p53 protein:
Degraded/absent p53: DNA damage → G1/S check point fk’d → cell goes through G1/S check point with shit DNA

2) E7 Phosphorylated Rb → Rb releases E2F transcription factor → E2F activated → transition of cell from G1 to S phase of cell cycle with damaged DNA

Question 29

What is p16?

Answer 29

p16INK4A is a CDK inhibitor: slows progression of the cell cycle by inactivating the CDK that phosphorylates retinoblastoma protein (preventing E2F release).

When E7 binds Rb, E2F is free/active (pushing cell from G1 to S), p16 is a negative feedback on this process. Therefore p16 is a marker of viral integration (E7 oncoprotein).

Question 30

When is p16 said to be positive?

Answer 30

p16 protein provide negative feedback to Rb to bind to E2F → over expression of p16 protein as marker for HPV (need ~ 70% cells stain for p16 to be considered positive)

Question 31

What is the current standard HPV vaccination:

Answer 31

HPV VACCINATION

Gardasil-9 (HPV 6, 11, 16, 18, 31, 33, 45, 52, 58) – require 2 doses, 90% coverage [standard vaccination for all 12 y/o in Australia]

Question 32

What are the criteria for a vaccination program?

Answer 32

Burden of disease
Effectiveness
Safe
Acceptability
- inconvenience/ discomfort versus benefit
Efficiency
- The balance between cost of vaccination and associated healthcare benefit
Priority
- Serves an urgent public health need at reasonable individual and societal cost

Question 33

Types of cervix biopsy:

Answer 33

Colposcopic biopsy - colposcopy to visualise cervix - inparticula the transition zone, then typically a punch biopsy(ies)

Endocervical curettage, also known as endocervical scraping and is performed as part of the colposcopic exam, especially if the cervix appears abnormal. It’s also done when the transformation zone isn’t visible with a colposcopy.

Cone biopsy (conization) cone of tissue:The cone may include tissue from both the endocervix, as the point of the cone, and the exocervix, as the base. The sample may also include the transformation zone. This type of biopsy is used to remove precancers completely and even treat cancer if it’s in an early stage. Cone biopsies are performed using either a scalpel or laser.

Question 34

What is CIN, what are the key features it captures?

When do we call it cancer?

A more modern description and its subtypes

Answer 34

Cervical Intraepithelial Neoplasm. Where the proportion of cervical epithelium exhibiting dysplastic cells determines grade:
CIN-1 (low-grade) involves the lower 1/3 or less of the epithelium, whereas the more significant CIN-2 and CIN-3 (high-grade) progress to include the entire thickness of the epithelium.

Dysplasia becomes cancer when it invades the basement membrane.

Question 35

What are the types of hysterectomy?

Answer 35

Class I a.k.a. “Simple” or “Extrafascial” hysterectomy: Removal of uterus and cervix, parametria left intact.

Class II a.k.a. “Modified-Radical” Hysterectomy: Removes uterus, cervix, 1–2 cm vagina, and WLE of parametria.

Class III a.k.a. “Radical” Hysterectomy: Removal of uterus, cervix, one-fourth to one-third of vagina, parametria divided at pelvic sidewall or sacral origin.

Question 36

The standard chemo in concurrent definitive chemoRT for locally advanced cervical cancer?

What is the benefit?

What are some alternatives?

Answer 36

Improves DFS and OS over RT alone:
Weekly cisplatin 40 mg/m2 has become standard of care.

Common alternative:
cisplatin/5-FU.
Other concurrent regimens:
weekly cisplatin + gemcitabine (increased pCR rate, PFS, and OS compared to cisplatin alone at the cost of very high acute toxicity).

Question 37

Is there a role for adj chemo in any cervix cancer setting?

Answer 37

1) Postop chemo RT improves OS in pts with +ve margins, parametrial involvement, and positive lymph nodes.

2) Adj CHTpost definitive chemoRT very recently studied by the large phase III OUTBACK Trial (GOG 274/RTOG 1174/ANZGOG0902) showing no OS or progression free benefit to additional adjuvant CHT, along with increased toxicity. For locally advanced disease.

Question 38

Argument in favour of Pelvic RT + brachy over surgery in early cervix cancer?

Answer 38

Milan study showed similar OS, however surgery tends to have higher morbidity.

The addition of chemo to RT further improves OS (confirmed on meta-analysis).

Question 39

What is the key cervix post-op chemo trial?

What are the criteria derived from this study?

Answer 39

Peters trial - OS benefit from post-op concurrent chemo IF ANY:
-+ve margin
+ve parametria
+ve node

High-risk post-op criteria (Peters Criteria):
-+ve margin
+ve parametria
+ve node

Question 40

Key cervix post-op RT trial, and criteria:

and alternative scoring system?

Answer 40

Sedlis Trial: For intermediate risk post op patients (Stage 1B) = node-negative, margin-negative, parametria-negative - there is a large 12yr progression free survival benefit (not powered for OS) to adj RT if 2 or more risk factors of: >1/3 stromal invasion, =>4cm or LVSI
(GOG scoring system is an even more complicated alternative).

Sedlis Criteria:
At least 2:
+LVSI,
Deep stromal invasion (>1/3),
tumor >4 cm,

Not included;
Adenocarcinoma

Question 41

Basic prescription (dose, modality) for a patient with a 2cm cervix adenocarcinoma, with 1cm DOI, confined to the cervix - excised via modified radical hysterectomy and PLND with clear margins, no nodes or parametria invasion, but LVI noted.

Answer 41

This patient has intermediate disease (Stage IB = confined to cervix - DOI>5mm), with no high risk features (Peters), and meets the Sedlis criteria for adj RT (i.e. adnoCa+ LVI).

Therefore I would treat with adjuvant EBRT VMAT technique the pelvis to 45Gy/25# (1.8Gy/#), 5 fractions a week. Targeting upper half of the vagina, and at risk pelvic nodes (obturator, external, internal and pre-sacral).

Question 42

What is the Embrace study?

Answer 42

A prospective non-randomised trial demonstrating the utility of MRI in brachy planning for locally advanced cervix ca.

Question 43

Basic prescription (dose, modality) for a patient with a 2cm cervix SCC, with 1cm DOI, confined to the cervix - excised via modified radical hysterectomy and PLND with +ve vaginal margins, no nodes or parametria invasion, but LVI noted.

Answer 43

This is high risk (Peters criteria) of recurrence disease - where the addition of chemo (Peters Trial) improves PFS/OS.

Therefore I would treat with adjuvant EBRT (concurrent w/weekly cisplatin) VMAT technique the pelvis to 45Gy/25# (1.8Gy/#), 5 fractions a week. Targeting upper 1/2 vag, and at risk pelvic nodes (obturator, external, internal and pre-sacral). ***The only dif from int risk is I’d consider common iliacs.

In selected patients w/ +ve or close vag mucosal margins, consider EBRT boost to vault (EQD2 54-60 Gy) or high HDR brachy boost.

SBRT is not routinely an appropriate alternative to brachytherapy boost.

Question 44

Benefit of chemo for metastatic cervix ca?

?What type

Answer 44

Doublet CHT shows better outcomes than single-agent therapy. Significant
improvement in PFS (2 months) and OS (3.7 months) with addition of bevacizumab to cisplatin/paclitaxel or topotecan/paclitaxel.

Question 45

When is definitive EBRT indicated in cervix cancer?

Answer 45

All cases stage ≥IA2 (and IA1 with LVSI) when treated non-operatively.

Question 46

What should be covered in a definitive EBRT plan?

Answer 46

Primary disease:
GTV + 0.5-1 cm.
Cervix and include whole uterus.
Parametrium.
If minimal or no extension, include upper half of vagina.
If upper vaginal involvement, include upper 2/3rd vagina.
If extensive vaginal involvement, include entire vagina.
If stage III and IV disease, include uterosacral ligaments.

Pelvis:
obturator nodes
external iliac lymph nodes
internal iliac lymph nodes
pre-­sacral nodes.
For high risk patients, consider inclusion of common iliac nodes.
If pelvic nodes involved, include common iliac nodes or at least 2 cm above highest involved node.
If common iliac nodes involved, include para-aortic nodes or at least 2 cm above highest involved node.

Question 47

At what dose does:
1) Infertility (women) occur?
2) Ovarian failure?

Answer 47

1) Infertility when >2Gy
2) Ovarian failure 5-10Gy

Question 48

Role of brachy in cervix ca:

Answer 48

1) Non-fert sparing mono therapy in 1A1 (<3mm DOI)
2) Vaginal cuff brachytherapy considered postoperatively following EBRT as vaginal apex boost in cases of close or positive vaginal margin.
3) From “bulky” (FIGO 1B = >5mm) tumours onwards EBRT + brachytherapy improves OS over EBRT alone even in setting of concurrent CHT.

Question 49

For cervix brachy, prior to first insertion what needs to be done and why?

Main brachy technique and alternative (when is this needed):

Answer 49

1) Clinical exam and imaging prior to 1st insertion allows selection of applicator.
2) Generally, intracavitary but interstitial may be necessary in certain circumstances (e.g, narrow anatomy cant fit intracavity applicator, wide lateral extent of disease, distal vaginal involvement, inaccessible cervical os).

Hybrid devices exist that combine intracavitary and interstitial components.

Question 50

What type of imaging should you plan cervix brachy on?

What CTVs should be contoured?

Answer 50

ABS 2012 guidelines recommend 3D imaging for volume delineation and planning.

MRI- based planning is preferred; better coverage of tumor, while potentially limiting dose to bladder, sigmoid, and rectum.

GEC-ESTRO guidelines define high-risk CTV (HR-CTV) and intermediate-risk CTV (IR-CTV) for 3D planning.

Question 51

Target volumes for cervix brachy:

Answer 51

GTVbrachy = Macroscopic tumour extension at the time of brachytherapy as detected by clinical examination and MRI imaging.

High risk CTVbrachy = GTVbrachy + whole cervix and the presumed extra cervical extension at the time of brachytherapy as detected by clinical examination and MRI imaging.

Intermediate risk CTVbrachy
HR CTVbrachy + safety margin of 0.5 -1.5cm.

Question 52

For cervix brachy what do you prescribe to?

Typical boost dose?

Answer 52

HR-CTVbrachy (D90):
Aim for a total dose of 90-95 Gy to HR-CTVbrachy EQD2 (α/β = 10, EBRT plus brachytherapy)

Aim for a total dose of 60 Gy EQD2 (α/β = 10, EBRT plus brachytherapy) to IR-CTVbrachy.

Typical boost dose = 24/3 (up to 30/5) 1-2 Delivered 1-3 days apart.

Question 53

Intended brachy dose coverage:

What should still be reported?

Answer 53

Intended dose should cover ≥90% of HR-CTV (D90).

<4 cm of residual disease :

EQD2 of ≥80 Gy (~5.5 Gy × 5 fx)

≥4 cm residual disease (or non-responders):
EQD2 of 85 to 90 Gy (~6 Gy × 5 fx) for

IR-CTV should receive ≥60 Gy. It is still required to report dose to point A.

Question 54

Common early toxicities for Cervix RT

Answer 54

Fatigue, diarrhea, rectal urgency, bloating/cramping, bladder/urethral irritation, skin erythema, and possible desquamation if inguinal LNs or distal vagina/vulva covered in fields.

Question 55

Common late toxicities for Cervix RT

Answer 55

Rectal bleeding, bowel obstruction, Hematuria,
Fistula (GI or urinary),
Vaginal ulceration/necrosis (5%–10% within 1 year, generally heals within 6 months with local care),
Vaginal stenosis (use dilators) and sexual dysfunction,
Infertility (~2 Gy),
Ovarian failure (5–10 Gy),
Osteopenia leading to hip and sacral insufficiency fractures.

Question 56

Should FIGO IB-IIA (define) patients be managed with surgery or RT?

Answer 56

Pts w/disease >2cm confined to cervix (B1, B2) or vagina (IIA) may be considered for either definitive option, and care should be tailored to Pt.

The advantages of surgery being: preserved sexual and ovarian function and elimination of secondary malignancy risk.

BUT older RCT data suggests radiation better tolerated, and a significant number of surg patients may require adj RT/chemoRT

Question 57

Does adjuvant hysterectomy following RT improve overall survival?

Answer 57

RCT evidence says no

Question 58

What does concurrent chemo add to RT in terms of benefit for cervix cancer patients?

Answer 58

Phase III evidence supports an OS benefit to the addition of cisplatin begining with bulky stage 1B3.

Question 59

For which patients cervix cancer patients should concurrent chemo be offered?

Answer 59

NCCN:
platinum-based CHT for “bulky” tumors (stage IB3, IIA2, and higher).

For stage IB1–2 and IIA1, CHT is optional.

For IA1 with LVSI or IA2 tumors, surgery is good option, but if treated nonoperatively, CHT can be omitted.

Question 60

What is standard concurrent CHT regimen in definitive cervix chemoRT?

Answer 60

Multiple single- and multi-agent regimens have been studied but currently single-agent cisplatin, given weekly, is most common.

Cisplatin/5-FU is common alternative.

Question 61

What is the impact of overall treatment time (OTT) on outcomes of patients treated definitively?

Answer 61

OTT for EBRT + brachytherapy should be ≤56 days. (A good thing to put in a treatment factors question).

Other OTT limits have been identified: ≤49 days; ≤63 days. Brachytherapy should begin no more than 7 days post-EBRT if downsizing of bulky disease is required.

Alternatively, for favorable anatomy or small primary tumor, practitioners can interdigitate brachytherapy during last couple weeks of EBRT.

It is generally recommended to avoid CHT and EBRT administration on brachytherapy days.

Question 62

Where is brachy point A?

Answer 62

Applicator placement formerly confirmed via AP and lateral films. Dose was prescribed to 2D point A (2 cm sup and 2 cm lat to os, in plane of tandem), roughly corresponding to medial aspect of broad ligament (where uterine artery and ureter cross).

Dose also estimated to point B (5cm lat to midline at level of point A), which represented pelvic sidewall/obturator LNs.

CT/MRI studies show adequate dose to point A not always indicates good cover of HR-CTV, and ICRU bladder and rectal points do not always accurately estimate max doses to these OARs.

Question 63

Role of cytology vs histology in cervix Ix

How is cytology classified

Answer 63

Cytology for screening (Pap smear), histology required for diagnosis confirmation.

Cytology grading: based on presence of koilocytes, nuclear enlargement and granulation, increase N:C ratio, mitotic count

Question 64

What are koilocytes?

Answer 64

Classic microscopic description of HPV infection of cervical epithelial cells is “koilocytosis.” Refers to the appearance of a perinuclear “halo” within the cell, along with enlarged and irregular nuclei that show evidence of mitosis. Hence:

1) Nuclear alteration (hyperchromasia, variation in nuclear size/ shape)
2) Perinuclear halo ( disruption of cytoskeleton)

Question 65

Histological grading for precursor cervix lesions:

Compare progression out comes

Answer 65

Histology grading: based on atypia and thickness of atypical cells from normal basal position.

Thickness of basal-like epithelium (to norm strat):
o CIN: <1/3 = CIN1, <2/3 = CIN2, >2/3 = CIN3
o CSIL: lower 1/3 = LSIL, upper 2/3 = HSIL

Dysplasia (CIN is older term, CSIL includes HPV status):
L(ow grade)SIL: Mild/moderate dysplasia. Only 10% progress to HSIL. p16 -ve

HSIL: mod to severe dysplasia, upper 2/3, p16+ve.
Up to 70% progress to invasive cancer in 5yrs

Question 66

Management of LSIL:

Answer 66

Most spontaneously resolve
10% progress to HSIL
Close surveillance typically recommended.

Question 67

Management of HSIL:

Answer 67

Up to 70% HSIL progress to invasive cancer in 5 years.

If confirmed on colposcopy or biopsy, needs excision or ablation of transformation zone.

Question 68

Compare cervix SCC and adenoCa -
Relative Incidence

Answer 68

Incidence:
SCC
- More common ~ 85%
- Decreasing incidence due to Pap-
screening and HPV vaccination
Adeno
- Less common ~ 15%
- More common in younger patients
- Increasing incidence (Pap-screening high
false negative for adeno → not picking pre- cursor lesions)

Question 69

Compare cervix SCC and adenoCa -
Risk factors

Answer 69

SCC:
HPV (HPV16 (59%), HPV18 (13%) , HPV58,33,45 ~5% each.

Adeno:
OCP use
HPV18 (38%)>HPV 16(33%)

Question 70

Compare cervix SCC and adenoCa -
Typical origin, macroscopic features:
Most common variant

Answer 70

SCC
- Usually arise from ectocervix
- Either exophytic or infiltrative

Adeno:
- Usually from endocervix
- Can be ‘barrel-shaped’ cervix (i.e. diffuse
infiltration), exophytic, flat/ plaque, usually ulcerated

Question 71

What causes a barrel-shaped cervix:

Answer 71

Cuased by diffuse infiltration of Adneocarcinoma

Question 72

Common variants of cervix SCC:

Answer 72

Subtype is prognostic
- Keratinizing
- non-keratinizing (worse the keratin)
- basaloid (worse prognosis)
- verrucous
- warty
- papillary

Question 73

Common variants of cervix adeno carcinoma:

Answer 73

• Mucinous adenocarcinoma (most common, 70-90% of adenocarcinoma)
• Endometroid adenocarcinoma
• Clear cell adenocarcinoma
• Serous adenocarcinoma

Question 74

Histological appearance of cervix SCC:

Answer 74

Atypical squamous cell, **keratinisation pearls, with intercellular bridging ** (Cf glands in adenocarcinoma)

Question 75

Histological appearance cervix adenocarcinoma

Answer 75

malignant cells with glandular differentiation, invades basement membrane and underlying stroma.

Question 76

Key features of a RADICAL HYSTERECTOMY PATHOLOGY REPORT (fucking caps lock):

Answer 76

1) Clinical details: Procedure, indication, specimens
2) Macroscopic details: Uterine dimensions, tumour (location, size, macroscopic invasion, gross margins)
Nodes number.
3) Microscopic: TYPE, Grade, margins, DOI, LVSI, parametrium, Node status
4) Ancillary tests: HPV, p16, IHC (e.g CK5/6+ for SCC, and CK7+ for adeno)

Question 77

Key cervix SCC IHC tests - whats the main one?

Answer 77

• CK5/6+ is pretty unique.
• Keratin +
• CEA+
• p53-ve (usually) (E6 protein degrade p53
  proteins)

Question 78

What 2 IHC tests are positive for both adeno and SCC of the cervix?

Answer 78

p16+, CEA+ (100%)

CK7+ is unique to adenocarcinoma.