Chapter 47: Cervical Neoplasia and Carcinoma

Question 1

How common is cervical cancer

Answer 1

• 3rd most common gynecological cancer here in the U.S., more common in countries that don’t screen for it
• Second most common cancer worldwide, first is breast cancer, and the most common cause of mortaliaity from gynecologic malignancy, accounting for 250,000 deaths per year

Question 2

How do we treat the precursor to cervical cancer, CIN?

Answer 2

-	Txs for CIN
o	Cryotherapy
o	Laser Ablation
o	LEEP: Loop electrosurgical excision procedure)
o	Cold-knife cone biopsy

Question 3

High grade strains of HPV

Answer 3

o High grade: 15 of em. 4 most common: 16,18,31,45

Question 4

Low risk HPV not associated with cancer

Answer 4

o Low risk not associated with cancer: 6 and 11
 Genital warts
 LSIL

Question 5

Where does HPV hit down in there?

Answer 5

o Hits at SCJ (squamocolumnar junction) 90% of the time where the nonkeratinized stratified squamous from outside meets the columnar mucus secreting cells inside

Question 6

Location of SCJ based on age

Answer 6

Childhood: Just inside external os

Puberty = Acidification + hormones = metaplasia of columnar cells so that junction moves OUTWARD onto cervical surface
o Location between old SCJ and new SCJ = Transformation zone.
o Nabothian cysts can form where squamous cells overrun glands from old columnar cells
o TZ cells, which are new and metaplastic, are most susceptible to oncogenesis, especially during puberty and early reproductive years when the metaplasia rate is highest

Perimenopausal: Recedes to internal os out of view

Question 7

HPV entering the genome vs not entering it

Answer 7

Most infection with HPV is transient, our body can kill it

 If HPV does not enter our genome, it just turns the cell it hit into a koilocyte, a withering looking cell with a pathetic looking nucleus that we see on histo
 If HPV does enter genome, we can get the gene changes that lead to transformation into pre-cancer or cancer

Question 8

Smokers and cervical cancer

Answer 8

o 3.5x greater in smokers – Products of smoking found in the cervix

Question 9

Common sense risk factors for cervical cancer (due to increase HPV, hint hint)

Answer 9

o More than one sex partner or a sex partner with more partners
o Intercourse younger than 18
o Male partner who has had a partner with cervical cancer
o HIV or other STDs
o Organ transplant, particularly kidney
o DES exposure (DURING pregnancy. We are beyond this now, those women are all in their 50’s now, but great test question)
o Infrequent PAP smears or history of HSIL/Cervical cancer

Question 10

Discuss in general what the 2001 Bethesda criteria is

Answer 10

 Divides into squamous lesions and glandular lesions, followed by pre-cancer and cancer.
 CIN 1,2,3 is the old system, but is still used today with the 2001 Bethesda update. The older system before that used mild, moderate, and severe dysplasia.

Question 11

Precancer vs Cancer squamos variety

Answer 11

Precancer:

1. Atypical squamous cells. Two types: ASC-US: Undetermined significance and ASC-H: Cannot exclude high grade
2. LSIL – HPV infection, CIN I, mild dysplasia and HSIL – CIN 2/3 (3 AKA carcinoma in situ or CIS) and moderate/severe dysplasia

Cancer: Invasive squamous carcinoma

Question 12

Precancer vs cancer glandular variety

Answer 12

Precancer:

1. Atypical (AGC) - (Endocervical, endometrial, or glandular cells)
2. Atypical, favor neoplastic (AFN) - (Endocervical and glandular cells)
3. Endocervical adenocarcinoma in situ (AIS)

Cancerous: Adenocarcinoma (Endocervical, endometrial, extrauterine, NOS (not otherwise specified))

Question 13

After abnormal PAP:

Answer 13

• After abnormal PAP, correlate with bimanual and visual inspection. Get HPV testing/cotesting and proceed to Colpo

Question 14

How does colpo work?

Answer 14

o Binocular stereomicroscope goes to 7-15x magnification. Green filter to help distinguish abnormal blood vessels. Easier to see changes/dysplasia and bx. Look for white areas, abnormal vasculature, punctate lesions

Question 15

Why do we use acetic acid in colpo

Answer 15

 Acetic acid 3-4% used to dehydrate cells, and those with big nuclei look white (big due to metaplasia, dysplasia or HPV infection). Wait 10-90 seconds.

Question 16

Unsatisfactory Colpo. What next?

Answer 16

o If SCJ not visualized or entire lesion not fully demarcated, Colpo is unsatisfactory

Proceed with cervical conization and endocervical curettage as indicated

Question 17

When do we do HPV testing?

Answer 17

• HPV testing done in women over 30 for high risk strains, non-adolescent LSIL patients, and anyone with ASC-US

Question 18

Ablation treatment options and the general point of it all

Answer 18

Get rid of CIN, the precursor lesion

Only do after PAP and correlated colpo and bx

Do laser or cryo. Electrofulguration also possible, as well as cold coag.

Question 19

Laser is rarely done anymore in the U.S. we tend to use Cryo. Discuss how this works

Answer 19

Used most commonly in outpatient clinic for persistent CIN I

o Cover SCJ and identified lesions with stainless steel probe, then supercooled with liquid nitrogen or compressed gas
o 3 minute freeze with 5 minute thaw and repeat freeze. First freeze kills superficial layers, thawing allows edema, second freeze freezes that mess getting deeper areas. Alow recovery for 4-5 weeks, may experience water discharge and passing of necrotic debris as the new cervical layer forms. Follow up PAP 12 weeks post-procedure
o Cure rate for CIN I approaches 90%

Question 20

Now on to the excisional methods. Problems with LEEP?

Answer 20

• LEEP may not be the best in glandular changes due to thermal damage to deeper cells

Question 21

Problems with CKC, LEEP, LLETZ in pregnancy

Answer 21

• CKC, LEEP, LLETZ all associated with 2nd trimester pregnancy loss secondary to cervical incompetence, pre-term labor, premature rupture of membranes, and cervical stenosis.

Question 22

Advantage of excision?

Answer 22

You get tissue to look at

Question 23

Biopsy/margin results from excision and what we do with them

Answer 23

 If positive margin, repeat conization or close follow up
 If positive margin with HSIL or CIS, hysterectomy if not wanting pregnancy. If wanting to remain fertile, colposcopy with ECC and HPV testing an acceptable management protocol
 Consider excising if ECC is positive, unsatisfactory colpo, or substantial discrepancy between PAP and histology of ECC and biopsy

Question 24

Follow up after ablation/excision

Answer 24

o Noninvasive abnormalities treated with excision or ablation need PAP follow up every 6 months for 2 years with return to routine screening thereafter

Question 25

CIN leads cancer by how many years?

Answer 25

10 years

Question 26

Average age of diagnosis for cervical cancer?

Answer 26

50

Question 27

> 90% of cervical cancers are due to

Answer 27

HPV

Question 28

Subtypes and prevalence of cervical carcinoma

Answer 28

o Squamos (80%) Adeno/Adenosquamos (15%)

Question 29

Symptoms of cervical cancer

Answer 29

o Symptoms: Watery discharge, postcoital bleeding, spotting. Often unrecognized

Question 30

Best biopsy option to diagnose something you think sould be cervical cancer

Answer 30

 FIGO based on histology, physical findings/lab findings showing extent
 Helpful due to predictable travel of cervical cancer: Goes to either the vagina or to parametrium and paracervical lymphatics. From Paracervical lymphatics to obturator, hypogastric, and common iliac lymph chains. Then to aortic lymph nodes

Question 31

FIGO Stage 1 means what

Answer 31

confined to cervix

Question 32

Discuss Stage IA of cervical cancer and what we do about it

Answer 32

IA: Invasive, defined by microscopy with invasion less than 5mm and extension less than 7mm

o A1: Stromal invasion

Question 33

Discuss Stage IB of cervical cancer and what we do about it

Answer 33

IB: Clinically visible lesions limited to cervix uteri or pre-clinical cancers larger than IA
o B1: Visible 4 cm

Tx: Radical hysterectomy with LN dissection or radiation therapy with cisplastin based chemo

Question 34

What’s going on with stage II cervical cancer?

Answer 34

Stage II – Cervical carcinoma invading beyond the uterus but not to pelvic wall or lower third of vagina

Question 35

Stage IIA and how we treat it

Answer 35

IIA: No parametrial invasion.

o A1: Visible 4 cm

o Tx: Radical hysterectomy with LN dissection or radiation therapy with cisplastin based chemo

Question 36

Stage IIB and how we treat it

Answer 36

IIB: Clear parametrial invasion

o Tx: External beam and brachytherapy radiation and concurrent cisplastin-based chemo

Question 37

Stage III of cervical cancer

Answer 37

 Stage III – To pelvic wall and/or lower one third of vagina and/or causes hydronephrosis or nonfunctioning kidney. If just lower third of vagina, IIIA, if one or both of the other two, IIIB

Question 38

Stage IV cervical cancer

Answer 38

 Stage IV - Beyond pelvis with biopsy proven results in bladder or rectum. IVA is adjacent organs, IVB is distant organs

Question 39

General target of radiation and how organs tolerate it?

Answer 39

o Brachyradiation uses tandem and ovioid devices through cervix and radiates primarily the lymphatic pathways
o Nearby structures like the bladder and rectum tolerate radiation well, but radiation cystitis and proctitis can occur, easily treatable

Question 40

Post cervical cancer treatment follow up

Answer 40

o Follow up exams every 4 months for 2 years
o Follow up exams every 6 months from 3 – 5 years.
o PAP smears as indicated for 20 years post procedure
o CXRs annually for 5 years

Question 41

5 year survival rates for cervical cancers

Answer 41

o	IA: 93%
o	IB: 80-90%
o	IIA/B: 58-63%
o	IIIA/B: 32-35%
o	IV: 15%

Question 42

When do we do the HPV vaccine?

Answer 42

First dose at elected date, second dose at 1-2 months after first dose, third dose 6 months after first dose

o Recommend starting at age 11-12. As young as 9, and as old as 26

Question 43

Two types of HPV vaccine and when we use them

Answer 43

o Two types: Gardisil (Quad) Cervarix (Bivalent)
 Gardisil against 16,18,6,11
 Cervarix against 16,18 and potentially 45, 31
 Sexually active can receive either
 Less effective if already with or exposed to HPV

Question 44

How does the vaccine work for HPV?

Answer 44

o Targets HPV-L1 structural protein, no DNAfrom HPV means you CANNOT get infected from the vaccine

Question 45

How good are these preventative measures at stopping cervical cancer?

Answer 45

o 40% reduction in incidence and mortality with cancer if you get routine PAPs, vaccines, follows protocols, etc.