Afsoon's Lecture Flashcards
Which of the following is true regarding the T-Zone?
A) Area where cervical neoplasia originates
B) Border between the stratified squamous epithelium of the ectocervix and columnar epithelium of the endocervix
C) A and B
D) Endocervical canal
C) Both A and B
The clinical scenario when HPV integrates into the genome is called:
A) Latent infection
B) Active infection
C) Neoplastic transformation
D) All of the above
C) Neoplastic transformation
Which of the following is not a cofactor in HPV pathogenesis?
A) Immunosuppression
B) Herpes and Chlamydia
C) Smoking
D) All of the above are cofactors in HPV pathogenesis
D) All of them are
First step in cervical cancer pathogenesis?
A) Persistence of HPV infection
B) Progression of a clone of epithelial cells from persistent viral infection to pre-cancer
C) Oncogenic HPV infectino of the metaplastic epithelium at the cervical transformation
D) Development of carcinoma and invasion through the basement membrane
This one was stupid. I think it’s oncogenic HPV infection of the metaplastic epithelium at the cervical transformation
Which cervical staging system is largely based upon physical examination and a limited number of endoscopic diagnostic procedures and imaging studies?
FIGO
What is the frequency of cervical cytology screening for age 21-29?
Every 3 years
18 year old presents for OCP’s. She has had annual paps since her pregnancy at age 16. She has had 7 partners since age 15 and a new partner for 3 months. What would you advise her about cervical cancer screening?
Pap test and HPV testing at age 21
25 yo comes in for first cervical cancer screening. Assuming pap is neg, when is her next screening?
3 years, pap or HPV testing
31 yo has not had a pap in 3 years. What is the recommendation for cervical cancer screening?
A) Co testing (pap/HPV) now and in 5 years
B)HPV testing in 3 years
C) No screening now
A) Co testing (pap/HPV) now and in 5 years
69 yo woman has no hx of abnormal paps. What would you advise her about cervical cancer screening?
No further pap testing is necessary if a woman is >65 yo and they have adequate negative screening results
Is HPV a DNA or RNA virus
DNA
Is HPV sufficient to cause cervical dysplasia
No, while necessary there needs to be other cofactors involved for dysplasia to occur
High risk types of HPV
16 and 18 (16 is more common). These types of HPV are more likely to persist.
Low risk types of HPV
6 and 11
HPV in women <30
Much more prevalent but less persistent. Most young women can clear the infection on their own
HPV in women >30
Much less prevalent but more persistent.
Duration of infection and HPV persistence
The longer an HPV infection has been recognized, the longer it will take to clear (if it clears)
Primary site of HPV infection
Cervical transformation zone (T-Zone)
Carcinogenesis for cervical dysplasia
Infection of the transformation zone with an oncogenic HPV subtype
Most common sx in low-risk HPV
Genital warts
Most common sx in high-risk HPV
Premalignant/malignant lesions
What does ASC-US stand for
Atypical squamous cells of undetermined significance (pathology for “we don’t know”)
What is the Transformation Zone (T-Zone)
Border between the stratified squamous epithelium of the ectocervix and the columnar epithelium of the endocervix.
What is the clinical significance of the T-Zone
Cervical neoplasia originates here
Latent HPV infection
Clinically asymptomatic. There’s no physical, cytologic or histologic manifestations
Active infection
Not cancerous!! The HPV virus is undergoing replication, but it isn’t integrating itself into the genome. Patient is not asymptomatic with the active infection.
Neoplastic Transformation
When the HPV virus is either an episome or a neoplasm
HPV Episome
Virus is hanging out and living/persisting in the cytoplasm
HPV Neoplasm
HPV virus is actively integrating itself into the host cell DNA
What determines an individual’s susceptibility to oncogenic HPV types
Their immune system!
Cofactors in HPV pathogenesis
Immunosuppression, cigarette smoking, herpes/chlam, OCP’s
How is cigarette smoking a cofactor?
Breakdown products of cig smoke cause cellular abnormalities in the cervical epithelium/a decrease in local immunity
HPV RNA Testing- what oncoproteins are we looking for?
E6 and/or E7 RNA
What does E6 mess with
Functions of p53 tumor suppressor gene
What does E7 mess with
Retinoblastoma protein
What does ASC-H mean
Atypical squamous cells, we cannot exlude it being a high grade squamous epithelial lesion
RF of cervical cancer
Early onset of sexual activity Multiple partner High risk partner Hx of STI Hx of vulvar/vaginal neoplasia/cancer Immunosuppression (HIV)
What is co-testing?
Testing cervical cytology (pap) and HPV screening at the same time.
What is Reflex HPV testing
Collecting a specimen for HPV testing after a pap has shown ASC-US results. ASC-US is undefined, but always needs more investigation
LAST criteria
Lower anogenital Squamous Terminology. Way of labeling the cervical dysplasia. CIN 0-3
CIN1
Low grade dysplasia. Active HPV
CIN
Cervical intraepithelial neoplasia. If 0, premalignant
CIN2
High grade dysplasia, active HPV
CIN3
Really high grade dysplasia, active HPV. Synonymous with CIS (carcinoma in situ)
When does CIS (carcinoma in situ) become metastatic
When it breaks through the basement membrane
Two ways of staging cervical cancer
FIGO and TNM.
FIGO scoring
Based on PE. More commonly used. No Stage zero!!
TNM
Classic tumor grading
Major prognostic factors affecting cervical cancer survival in women
Disease stage and LN status
CIN Primary Prevention methods
Pap smears and HPV vaccination
CIN Secondary Prevention methods
You have cancer at this point, we’re trying to keep it from becoming advanced and save your life.
When is the HPV vaccine most effective
If you have never been exposed to HPV
Who is the 9-valent HPV vaccine recommended for
Females aged 11-12. You can give it as early as 9 though
Use for quadrivalent or 9-valent HPV vaccine
For prevention of anal cancer, precursor lesions, genital warts.
9-valent specific is cervical/vaginal/vulvar cancer
Who is the “catch up vaccine” for?
Women aged 13-26 who have not been previously vaccinated or did not complete the vaccination series
Getting the vaccine at <15 yo
2 HPV doses 6 months apart
Getting the vaccine at >15 yo
3 HPV doses in a max of 2 years
Pathogenesis of Cervical Cancer
1) Oncogenic HPV infection at the T Zone
2) Persistence of so-said HPV infection
3) Progression of viral infection to pre-cancer
4) Development of carcinoma and invasion into the basement membrane
What two ways can cervical cancer spread?
Direct extension or by lymphatic/hematogenous dissemination
What does spreading by “direct extension” mean?
Directly spreading to the uterine corpus, vagina, peritoneal cavity, bladder or rectum
Clinical manifestations of cervical cancer?
Irregular/heavy vaginal bleeding and postcoital bleeding
Steps to diagnosing cervical cancer
1) PE
2) Cervical pap cytology smear (GOLD STANDARD)
3) Have lesions or an abnormal pap? Do a colposcopy w/ directed bx
4) Suspected cancer but got nothing from the directed biopsy? Cervical conization time.
What kind of lab tests do we want to order when considering cervical cancer?
CBC
LFT/RFT
UA
Tumor markers
HPV vaccine in males?
Literally the same exact guidelines as for women. Routinely use quadrivalent vax
Pregnant w/ ASC-US?
Defer colposcopy 6 weeks PP
Pregnant w/ ASC-H?
Do not defer. Do the colposcopy, but do not do endocervical curettage. Just do it with the cytobrush, it’s wicked gentle.
Most specific presentation of cervical cancer
Post coital bleeding.
Pap screening reduction in cervical cancer MM
80%
Where do we do a pap smear?
T zone
According to ACOG, when should we start screening women?
> 21 years old. Young women were getting over txed for HPV infection that would almost always clear on their own
According to ACOG, how do we manage women from age 21-29
We do either HPV or a cytology screening every 3 years
According to ACOG, how do we manage women >30 years old
Either
1) Cotesting every 5 years
2) Same shit as when they were >21
According to ACOG, when can we consider cessation of screening in a 65 year old woman
If the woman has had no previous HPV infection, 2 consecutive negative cotesting or 3 negative paps in the last 10 years
According to ACOG, in what case would we keep screening a woman until she is 80 yo
If the patient has had any hx of CIN2 (high grade dysplasia)
Methods of biopsying the cervix
1) Colposcopy
2) Cone biopsy (usually done during colposcopy, it’s gold standard!)
3) LEEP (Loop electrosurgical excision procedure)
4) Cryosurgery
5) Endocervical curettage (take out a little scoop)
When do we do endocervical curettage
When endometrial/cervical cancer is suspeted or needs to be ruled out. Usually done during colposcopy
Evaluating ASC-US in a woman >25
Reflex testing for HPV.
Negative? Do cotesting in 3 years
Postive? Colposcopy
Evaluating ASC-US in a woman 21-24
Still young. Repeat the pap in 12 months.
Cytology negative/ASC-US or LSIL? Repeat the pap in another year. Do this for two years.
Cytology is ASC-H? Do a colposcopy
Evaluating ASC-H in a woman >25
Do a colposcopy.
1) No lesion/CIN1? Do cotesting every year for two years. If both are negative resume routine screening. if HPV pos/HSIL do a colposcopy
2) CIN2 or CIN3? Treatment (LEEP)
Evaluating ASC-H in a woman 21-24
Cytology & colposcopy every 6 months for a year.
1) Negative? Cotest in another year
2) Abnormal after one year? Repeat biopsy
3) Abnormal after two years? Tx. LEEP
Evaluating CIN
Need follow up.
1) Persistent CIN1 for 2 years? LEEP
2) CIN 2/3? LEEP
After treating CIN1/2/3 how should we follow up
Do cotesting once a year for 2 years
Post LEEP management of CIN2/3
Co testing every 12mo/24mo.
1) Negative? cotesting is repeated in 3 years. Still negative? Rad, just go back to normal screening.
2) Postive cytology or HPV? Colposcopy w/ endocervical curettage.
