Cervix

Question 1

What social factor is most likely to affect prognosis in cervical cancer?
A) Race
B) Obesity
C) Hypertension
D) Diabetes

Answer 1

Race - minorities likely to present later at a higher stage because of lack of access to care.

Question 2

What is the best imaging modality for pelvic lymph nodes in cervix cancer?

Answer 2

PET/CT

Question 3

What is the taxonomic family of HPV? Genus?

Answer 3

Papillomaviridae
Alphapapillomavirus (at least 6,11,16,18)

Question 4

What type of virus is HPV?

Answer 4

small non-enveloped, dsDNA virus in an icosahedral protein capsid with circular DNA

Question 5

What are high risk oncogenic HPV subtypes?

Answer 5

16, 18, 45, 31, 33, 35, 52, 58

Question 6

What are the intermediate risk but likely still oncogenic HPV subtypes?

Answer 6

39, 51, 56, 59, 66, 68, 73

Question 7

What are the low risk HPV subtypes? (Associated with condyloma acuminata)

Answer 7

6, 11
Unable to integrate into the human genome

FYI others from Chi: 42, 43, 44

Question 8

What is the role of early proteins E1 and E2 in the HPV virus?

Answer 8

E1 is a helicase that unwinds the viral origin and recruits host cellular factors to replicate the viral genome.

E2 is a transcriptional regulator (activator and repressor).

Together they are involved in integration of the viral genome into the host cell genome.

Question 9

What does the early protein E4 encode in the HPV virus?

Answer 9

E4 is involved in HPV replication: the maturation of viral particles and preparing them for release from the cell

Question 10

What is the function of E6 and E7 early proteins?

Answer 10

Immortalization of keratinocytes

Involved in cellular transformation, leading to genomic instability.

E6 binds p53 tumor suppressor, causes p53 degradation —> removes G1/S checkpoints.
E6 also increases telomerase activity in keratinocytes by increased transcription of the human telomerase catalytic subunit (hTERT) via induction of c-myc.

E7 binds Rb tumor suppressor (normally binds E2F, which inhibits cellular proliferation) —> uncontrolled cell cycle proliferation (responsible for imortalizing infected cells).
E7 is the primary transforming protein.

Question 11

What does HPV E6 early protein bind?

Answer 11

p53

Question 12

What does HPV E7 early protein bind?

Answer 12

Rb

Question 13

What do the late proteins L1/L2 encode in the HPV virus?

Answer 13

viral capsid proteins - important for virus infectivity
Vaccine contains L1 protein which make VPL

Question 14

What is the best test to detect HPV?

Answer 14

PCR

Question 15

After HPV infection, what mutations may lead to cervical cancer?

Answer 15

Aberrant expression of viral oncogenes and concomittant inactivation of host tumor suppressor genes is not enough to develop cervix cancer. Additional mutations are accumulated over time, such as RAS mutation and c-Myc amplification.

Question 16

What kind of virus is HPV?
A) double stranded DNA
B) double stranded RNA
C) single stranded DNA
D) single stranded RNA
E) retrovirus

Answer 16

double stranded DNA

Question 17

Worst prognostic factor for being able to complete radical trachelectomy:
A) tumor size < 2cm
B) focal lvsi
C) adenosquamous
D) endocervical extension
E) grade

Answer 17

D) endocervical extension

Question 18

What is the latest cervix cancer stage eligible for radical trachelectomy?

Answer 18

IB1 2cm or less

Question 19

Best imaging for stage IIB cervix?

Answer 19

MRI vs. PET/CT

Question 20

Systemic treatment for metastatic cervix cancer?

Answer 20

Carbo/taxol/bev
or
Cis/taxol/bev

up to date: programmed cell death ligand 1 (PD-L1) expression combined positive score (CPS) ≥1, we recommend the addition of pembrolizumab

Question 21

Tx of microinvasive cervix cancer

Answer 21

CKC if fertility desired or simple hyst if fertility not desired

Micro invasive disease: IA1 without LVSI
IA1: microscopic disease with DOI ≤3 mm in depth

Question 22

Tx for IVB cervical cancer

Answer 22

Real answer Cis or carbo /taxol/bev +/- pembro (KN826)
A little older answer: GOG 240: Cis/taxol/bev

GOG204 cis/taxol won out of cis/vinorelbine, cisgem, cis/topo

JGOG0505 says carbo/taxol ok

Question 23

Treatment of stage IVB cervix cancer with bleeding

Answer 23

Chemorads
(Can do hyperfractionated rads to stop bleeding, then systemic chemo)

Question 24

HPV+ patient, what is the most important cofactor in developing HPV infection?
A) Smoking
B) OCP use
C) Multiple partners
D) Age at first coitus

Answer 24

A) Smoking

Question 25

What is the role of PET in cervix cancer?
A) Assess for bladder involvement
B) Assess for distant mets
C) Assess for side wall involvement

Answer 25

B) assess for distant mets

Question 26

Pregnant pt, cone bx stage IA1 squamous cervical cancer neg margins - next step

Answer 26

observe

Question 27

Pregnant pt cone bx CIS, + margins, pos ECC - next step?

Answer 27

observe

Question 28

Most common HPV type with ADENOCARCINOMA of the cervix

Answer 28

18

Question 29

Cvx cancer 6 mm wide, 2.5 mm deep, CKC with neg margins (question doesn’t give LVSI status), wants fertility preservation - next step?
A) Hyst/rad hyst
B) obs
C) rad trachelectomy with LND
D) repeat CKC

Answer 29

B) observe

Question 30

Immediate tx for hyperkalemia in Stage III cerivcal cancer pt

A) lasix (loop diuretic)
B) insulin/glucose
C) dialysis
D) kayexelate

Answer 30

B) insulin/glucose

(calcium gluconate is not an answer choice here, but should also be given to protect/stabilize cardiomyocytes)

Question 31

Criteria for trachelectomy

Answer 31

1. Desire to preserve fertility
2. Reproductive age
3. Squamous or adeno (i.e., not neuroendocrine)
4. Stage IA1 with LVSI, IA2, or IB1
5. Lesion </= 2 cm with limited endocervical extension on colpo and MRI
6. No evidence of LN mets

(Note: LVSI itself is not a contradication)

Using these: 10-12% end up abandoning trachelectomy due to +endocx margin, larger lesion, or positive nodes on frozen

Question 32

Contraindication to radical trachelectomy
A) LVSI
B) size 3 cm
C) adenocarcinoma
D) multip

Answer 32

B) size 3cm

Question 33

What histology is a contraindication for radical trachelectomy
A) Small cell
B) villous glandular adenoma
C) mucinous adenocarcinoma

Answer 33

A) small cell

(Neuroendocrine types: typical carcinoid, atypical carcinoid, small cell, and large cell. Neuroendocrine histology is a CI to trachelectomy)

Question 34

Which was most likely to have ureteral obstruction:
A) RT then extrafascial hyst
B) rad hyst then RT
C) EBRT
D) VBT

Answer 34

B) rad hyst then RT

Question 35

What is the best adjuvant treatment for a pt s/p rad hyst with positive parametria?

Answer 35

Pelvic RT + chemo

(Peters criteria: +LN, +margin, +parametria got Cis 70mg/m2 and 5-FU q3wk x 4 cycles)

Question 36

Cervical adenoma malignum is associated with what syndrome?

Answer 36

peutz jeghers syndrome

STK11 mutation

Question 37

Risk of Pelvic LN mets by stage of cervix cancer

Answer 37

stage IA1 - 1% any
stage IA2 - 7% any
stage IB - 15%
stage II - 25-45%
stage III - 45-60%
USE CHART

Question 38

Risk of PaLN mets by stage of cervix cancer

Answer 38

stage IB - 5%
stage II - 15-20%
stage III - 30%
stage IV - 30%

Question 39

DES exposure for CHILDREN - how much higher risk vaginal clear cell?

Answer 39

40x

(the MOTHERS do not have any increased risk)
mother use have risk of breast ca

risk 1/1000 vs population 2.5/100,000 (1/40,000)

Question 40

Type of bladder malfunction after radhyst

Answer 40

Neurogenic (retention)

Question 41

Pregnant with 1B1 cervix cancer at 32 weeks, next step:
A) C-rad-hyst
B) SVD
C) test for fetal lung maturity

Answer 41

A) C-rad-hyst

? C based on Chi: “For stage I disease, radical hysterectomy can be safely performed at a gestational age >20 weeks when fetal lung maturity is documented and a third-trimester cesarean section is planned”

Question 42

Which imaging study best correlates with final size on path in cervix ca?

Answer 42

MRI

Question 43

How did adding bev affect quality of life for cervical cancer treatment?

Answer 43

Did not affect QOL (no worse)

Question 44

32yo P3 desires fertility, has 3 cm cervical cancer. Best radical surgery in addition to lymph node assessment?
A) Robotic trachelectomy
B) robotic hysterectomy
C) abdominal trachelectomy
D) abdominal hysterectomy

Answer 44

C) abdominal trachelectomy (this one ok per NCCN but most validated in tumors < 2cm)

NCCN: Fertility-sparing surgery for stage IB has been most validated for tumors ≤2 cm. For stage IB2 lesions 2–4 cm, abdominal approach is favored. Small cell neuroendocrine histology and gastric type adenocarcinoma are not considered suitable tumors for this procedure.

Question 45

Point A
Point B
(Manchester system)

Answer 45

Point A = 2 cm lateral to the center of the tandem and 2cm superior to the vaginal fornix in the plane of the implant. (where ureter crosses uterine artery, avg point from which to assess dose in paracervical region)

Point B = 5 cm from midline at level of point A aka 3 cm lateral to point A (correspond to obturator nodes)

The Manchester system is the most common system used in intracavitary brachytherapy for cervical carcinoma.

Question 46

Best imaging for localizing recurrent cervix

Answer 46

PET/CT

Question 47

29yo with 6cm cervical mass, has received 10Gy, and has a right TOA. Next step?
A) rad hyst
B) USO/BSO
C) LND
D) continue RT

Answer 47

B) USO/BSO
Need to remove source of infection, due to patient being on treatment and being immunocompromised, risk of fistula, etc.
TD50 of the ovary is 1000cGy (10Gy), so can consider taking the other ovary or pexing it (50% chance it is ok)