LM 9.2: Cervical Cancer

Question 1

what organism mostly causes cervical cancer?

Answer 1

HPV is the causative agent of >99% of cervical neoplasia and cancer

Question 2

what type of organism is HPV?

Answer 2

double stranded DNA virus

> 150 distinct types, of which 40 infect the lower genital tract

the most common STI in the US

Question 3

how does HPV infect people?

Answer 3

it infects squamous or metaplastic epithelial cells by accessing the basement membranes via a break in the skin’s surface

most sexually active adults are infected at some point during their life time. (80% of women will be infected with hrHPV by the age of 50)

infection is usually cleared by host immune system – the majority of women will not be symptomatic from their infection

Question 4

which HPV strains are high risk?

Answer 4

Infection is usually cleared by host immune system. The majority of women will not be symptomatic from their infection

hrHPV 16—associated with 60% of cervical cancer

hrHPV 18 associated with 10-15% of cervical cancers

Question 5

which HPV strains are low risk?

Answer 5

HPV 6 and 11

associated with genital warts and laryngeal papillomas – rarely associated with cancer

included in HPV Vaccine

Question 6

which HPV strain is associated to oropharyngeal cancers?

Answer 6

60-70% of oropharyngeal cancers are thought to be linked to HPV, especially hrHPV 16

Question 7

do you test for HPV?

Answer 7

testing should not be done for low risk HPV

not recommended for screening in women under the age of 30 unless it is in the case of triaging cervical cytology

not recommended in women who have had a total hysterectomy (references that the cervix was removed with the uterus)

Question 8

how do you test for HPV?

Answer 8

detection of HPV nucleic acids using NAAT and PCR testing

Question 9

what are the risk factors for HPV?

Answer 9

1. low socioeconomic status
2. latin america or US minorities
3. increasing age
4. early sex
5. multiple sexual partners
6. tobacco smoking
7. dietary deficiencies
8. exogenous hormones
9. parity
10. immunosuppression

Question 10

what do you do if someone has a visible cervical lesion?

Answer 10

biopsy!!!!!

a pap smear can be negative in the presence of a visible cervical cancer!

Question 11

when would you do a colposcopy if there is abnormal pap smear?

Answer 11

colposcopy is a procedure done to identify the lesion causing the abnormal pap smear

the intent is to perform a colposcopically directed biopsy of lesions to define the severity and location of disease

it’s a binocular magnification tool on a stand to provide viewing of the cervix used for evaluation of the abnormal cervical cancer screening result or a visible lesion

Question 12

what are low grade squamous intraepithelial lesions?

Answer 12

LSIL lesions are now recognized as having a low probability of progressing to HSIL and cancer

LSIL is a low grade cervical dysplasia that is highly likely to resolve spontaneously

treatment is not indicated unless persists more than 2 years.

Question 13

what are high grade squamous intraepithelial lesions?

Answer 13

considered to be disease state reflective of hrHPV infection leading to dysplastic change –> dysplastic cells occupy >1/3 of the epithelial thickness

most common treatment is excision of the transformation zone using either a cold knife cone or LEEP

also require investigation due to high association with high grade lesions on biopsy

in young women, you can just observe closely with pap and colposcopy for regression/progression –> avoid ablative/excisional therapy when possible

at risk for progression to cervical cancer if left untreated

Question 14

what is p16 staining?

Answer 14

an immunostaining technique that identifies active oncogenic HPV

when CIN 2 is noted on cervical biopsy, p16 staining is done –> CIN 2 is sorted into LSIL if p16 is negative and into HSIL if p16 staining is positive

P16 staining is a marker for high risk (oncogenic) HPV and presence of p16 moves the CIN2 to HSIL classification and management

absence of p16 moves the CIN 2 to LSIL classification and managment

Question 15

how do you treat high grade squamous intraepithelial lesions?

Answer 15

HSIL treatment is determined by the results of the biopsy and colposcopy evaluation of the cervix

in general, in women over the age of 24, CIN 2 or CIN3 will be recommended an ablative or excisional treatment –> the most common choice is excisional treatment as it not only removes the abnormal area(s), but provides a pathology specimen to assure there is no missed cancer diagnosis

hysterectomy is unacceptable as primary therapy for CIN but it is the preferred treatment for adenocarcinoma in situ

Question 16

what is cervical adenocarcinoma in situ?

Answer 16

multifocal (“skip lesions”) that can be located deep in endocervical clefts or deep in the canal

difficult to identify on colpsopscopy

less common than squamous cell dysplasia or cancer but incidence seems to be increasing

hysterectomy is treatment of choice but excisions therapy can be attempted for patients who want to preserve fertility

Question 17

what is the follow up care for an excisions procedure?

Answer 17

return in 2-4 weeks to assure appropriate healing and to review the pathology report

then return in one year for a pap and hrHPV test—if both are negative, they will return again in one year

if hrHPV or Cytology is abnormal, a colposcopy is indicated to assess for persistent disease

so even though excisional procedures have a high rate of success, surveillance post procedure is critical

Question 18

what are the general characteristics/facts about cervical cancer?

Answer 18

1. historically, It was a leading cause of cancer death in women in the US
2. 3rd most common cause of cancer death world wide (especially in developing countries)
3. cervical cancer death rate is down by more than 50% over the last 40 years
4. now it is the #14 occurring cancer in US women (Breast is most common, followed by lung and colon cancers. Lung cancer is the leading cause of cancer deaths in women)
5. when referencing cervical cancer screening, the true goal is not just identification of cervical cancer, but of pre-cancerous lesions (asymptomatic)
6. identification and treatment of pre-cancerous lesions can prevent development of cervical cancer.
7. 99% caused by HPV infection
8. ½ of women diagnosed with cervical cancer had no or inadequate screening

Question 19

what are the risk factors for cervical cancer?

Answer 19

1. low SES
2. latin american or minotiries
3. increasing age
4. early sex
5. multiple partners
6. tobacco
7. dietary deficiencies
8. cervical HPV infection
9. exogenous hormones
10. parity
11. immunosuppression
12. inadequate screenin *****GREATEST risk factor

Question 20

what are the 2 types of cervical cancer?

Answer 20

1. squamous cell carcinoma

most common cell type, 64.9%; associated with HPVHR

2. adenocarincoma

29% of cervical cancers; associated with HPV especially 16/18

pap smear can’t detect this lesion and it tends to be multifocal

it arises from the endocervical mucus producing columnar cells

Question 21

what is the clinical presentation of cervical cancer?

Answer 21

1. intermittent vaginal bleeding/spotting
2. post coital bleeding
3. persistent discharge without other diagnosis
4. pelvic pain
5. vary and can be non-specific

Question 22

what are the clinical findings associated with cervical cancer?

Answer 22

1. normal appearing cervix
2. abnormal pap
3. friable cervix
4. exophyti cervical lesion
5. endophytic cervical lesions
6. lesion confined to the endocervix, may not be visible or palpable

Question 23

how do you diagnose cervical cancer?

Answer 23

tissue diagnosis is essential prior to embarking on treatment

Question 24

how do you stage cervical cancer?

Answer 24

clinically with PE, tissue biopsy or cold knife cone, CXR, or imaging of ureters

surgical findings are not used to change the staging, although may be used to optimize treatment planning

Question 25

what is stage 1 cervical cancer?

Answer 25

carcinoma is strictly confined to the cervix

IA Invasive cancer identified only microscopically. (All gross lesions even with superficial invasion are Stage IB cancers.) Invasion is limited to measured stromal invasion with a maximum depth of 5 mma and no wider than 7 mm.

IA1 Measured invasion of stroma ≤ 3 mm in depth and ≤ 7 mm width.

IA2 Measured invasion of stroma > 3 mm and <5 mm in depth and ≤ 7 mm width.

IB Clinical lesions confined to the cervix, or preclinical lesions greater than stage IA.

IB1 Clinical lesions no greater than 4 cm in size.

IB2 Clinical lesions > 4 cm in size

Question 26

what is stage 2 cervical cancer?

Answer 26

carcinoma extends beyond the uterus, but has not extended onto the pelvic wall or to the lower third of vagina

IIA Involvement of up to the upper 2/3 of the vagina. No obvious parametrial involvement.

IIA1 Clinically visible lesion ≤ 4 cm

IIA2 Clinically visible lesion > 4 cm

IIB Obvious parametrial involvement but not onto the pelvic sidewal

Question 27

what is stage 3 cervical cancer?

Answer 27

carcinoma has extended onto the pelvic sidewall

on rectal examination, there is no cancer free space between the tumor and pelvic sidewall

tumor involves the lower third of the vagina

IIIA Involvement of the lower vagina but no extension onto pelvic sidewall.

IIIB Extension onto the pelvic sidewall, or hydronephrosis/non-functioning kidney

Question 28

what is stage 4 cervical cancer?

Answer 28

carcinoma has extended beyond the true pelvis or has clinically involved the mucosa of the bladder and/or rectum

IVA Spread to adjacent pelvic organs. IVB Spread to distant organs.

IVB Spread to distant organs

Question 29

how do you treat cervical cancer?

Answer 29

1. surgery eligibility is determined by staging and clinical circumstances
2. radiation
3. chemo

Question 30

what is the followup for cervical cancer after treatment?

Answer 30

monitoring for persistence and recurrence with clinical exams or imagining studies/pap smears

monitoring for complications of treatment like fistulas, radiation cystitis, radiation colitis, vaginal atrophy, vaginal shortening

Question 31

how do you prevent cervical cancer?

Answer 31

1. HPV caccination
2. sexual abstinence
3. nbarrier protection
4. regular cytologic and hrHPV screening
5. condoms

Question 32

what types of HPV vaccines are there?

Answer 32

1. quadrivalent (6,11,16,18)
2. nanovalent (6,11,16,18,31,33,45,52,58)

ideally provided prior to initiation of sexual activity

previous exposure to HPV is not a contraindication to receiving the vaccine

not recommended in pregnancy but safe in lactating patients

those who have been vaccinated should still participate in a cervical cancer screening program