11/2- HPV and Cervical Cancer Flashcards
(50 cards)
1
Q
How are HPV infections classified?
A
High risk vs. low risk based on their oncogenic potential
2
Q
Which strains of HPV are especially high-risk for cancer?
- Warts?
A
Cancer:
- 16, 18
- 31, 33
- many more
Warts:
- 6
- 11
- 40
- 42
- many more
3
Q
What tissues does HPV infect?
A
HPV causes epithelial tumors of the skin and mucous membranes
- May be latent, subclinical…
4
Q
Describe the structure of the HPV virus?
- Envelope?
- DNA vs. RNA
A
- Non-enveloped
- Double stranded circular DNA
5
Q
How does HPV infect the cell?
- How does it spread?
A
- Can integrate into host DNA (E6 and E7 proteins inactivate p53 and Rb)
- Infects the basal keratinocyte of the epidermis
- Spreads via skin contact
- Survives for months and at low temperatures
6
Q
T/F: HPV is the most common STD in the world
A
True
7
Q
Female to male prevalence of HPV?
A
F > M (but only by about 1.4x)
8
Q
What is the prognosis of HPV?
A
- Good prognosis with both recurrences and regressions possible
- 2/3 of cutaneous warts regress within 2 years
- Genital warts may regress, remain unchanged or increase in size
- 90% of infections with HPV are thought to clear in 2 years
- Anogenital infections in females are associated with the development of vulvar, vaginal, and cervical dysplasia and cancers due to long-term persistent infections
9
Q
What is the original squamocolumnar junction?
A
Junction where the columnar epithelium meets the squamous epithelium on the ectocervix (at birth)
10
Q
What happens regarding the jungtion during adolescence and pregnancy?
A
Metaplasia
- The junction of the columnar epithelium and the squamous epithelium moves proximally into the endocervix and is called the new squamocolumnar junction
11
Q
What is the transformation zone?
A
The area between the original and the new squamocolumnar junction
12
Q
What are the 2 types of screening?
A
Conventional Pap Smear
- Cervical cell sample manually “smeared” onto slide for screening
Liquid-Based
- Cervical cell sample put into liquid medium for suspension before automated thin layer/monolayer slide preparation
- ThinPrep
- SurePathTM
13
Q
High risk HPV has been implicated in __% of cervical cancers
A
High risk HPV has been implicated in 90% of cervical cancers
14
Q
What can be use din conjunction with pap smears for cytology screening?
A
HPV genotype testing
15
Q
How were these specimens collected?
A
Left: cytologic finding via pap smear
Right: histologic findings via cervical biopsy
16
Q
Describe a colposcopy
A
- Binocular microscope with low magnification (10 to 40x) used to visualize the cervix;
- Usually prepared with acetic acid to help in identifying lesions
17
Q
How can you obtain a cervical biopsy/endocervical curettage?
A
- Punch biopsy
- Scraping of endocervical cancal
18
Q
What are the screening recommendations for HPV?
A
- < 21: screening should not be done
- 21-29 yo: cervical cytology every 3 yrs - 30-65 yo:
- Cotesting with cervical cytology and HPV testing ever 5 yrs OR
- Cervical cytology every 3 yrs
- > 65 yo: no screening necessary (unless hx of CIN2, CIN3, AIS or cancer; then follow 20 yrs after Dx)
- Women with total hysterectomy: no screening necessary (same exceptions as above)
- Vaccinated women: routine screening as above
19
Q
What are risk factors for cervical dysplasia?
A
- HPV infection
- Sexual activity
- Increased number of recent/lifetime partners
- Early onset of sexual activity
- Increased number of pregnancies
- HIV
- Immunosuppressed status
- Smoking
- Hx of other STDs (HSV, Chlamydia, bacterial vaginosis)
- Long term oral contraceptive use
- Low SES
20
Q
How to classify an abnormal pap smear (don’t have to memorize)?
A
1. Statement regarding the adequacy of the pap smear
2. Diagnostic categorization (normal or other)
3. Descriptive diagnosis
- Atypical squamous cells of undetermined significance (ASCUS)
- Atypical squamous cells of undertermined significance cannot exclude high grade lesion (ASC-H)
- Low-grade squamous intraepithelial lesion (LGSIL)
- High-grade squamous intraepithelial lesion (HGSIL)
- Squamous cell carcinoma
- Atypical glandular cells (AGC)
- Endocervical adenocarcinoma in situ (AIS)
- Adenocarcinoma
21
Q
What are the risks for different classifications proceeding to a worse stage/cancer?
A
HSIL > LSIL > ASCUS
- ASCUS normally regresses to normal (68%), but 7% progress to HSIL in a year and 0.25% progress to invasive cancer in 24 mo
- LSIL regresses to normal 47% of the time, to HSIL 21% and to cancer 0.15% in a year
- HSIL regresses to normal 35% of the time, to HSIL 24% and invasive cancer 1.4% in a year
22
Q
Describe the appearance of cervical intraepithelial neoplasia
A
- Abnormal epithelial proliferation and maturation above the basement membrane
- Ranges from mild dysplasia to severe dysplasia
- CIN 1: Involvement of the inner 1/3
- CIN II: Involvement of the inner ½ to 2/3
- CIN III: Full thickness involvement
- Cancer if it invades through basal membrane! (pic 407)
23
Q
What are the odds of CIN1-3 regressing, persisting, progressing to CIS, or invading?
A
24
Q
How do you treat intraepithelial neoplasia?
A
- If CIN1, just observe with active treatment, because many spontaneously regress
- CIN II and III are often actively treated
- Hysterectomy is almost never indicated for CIN treatment (NOT anymore; surgical risks, very invasive)
- Recommendations made by American society for Colposcopy and Cervical Pathology (ASCCP)
25
What are some ablative techniques?
- Cryotherapy
- Laser Vaporization therapy
26
Describe cryotherapy
- The use of a probe containing CO2 (carbon dioxide) or NO (nitrous oxide) to freeze the entire transformation zone and area of the lesion
- Different sizes of probe available
27
Describe laser vaporization therapy
- The use of a laser to vaporize the transformation zone containing the lesion
- Requires suction to remove smoke
- Different power levels are available
28
What are excisional techniques for CIN?
Conization
- Cold Knife Cone
- Laser Conization
- LEEP (Loop Electrosurgical Excision Procedure)
29
Which techinque is preferred for CIS (Carcinoma in Situ where all the cells look abnormal)?
Cold Knife Zone
30
Describe Conization
Conization
- A cone of tissue is excised for further examination and/or to remove a lesion
- The tissue is usually stained with iodine (Lugol’s or Schiller’s solution) to demarcate the area of resection
31
Describe the subtypes of conization:
- Cold Knife Cone
- Laser Conization
- LEEP (Loop Electrosurgical Excision Procedure)
**Cold Knife Cone**
- The use of a scalpel or “cold knife cone” since no electrosurgical current is used
**Laser Conization:**
- The use of a laser for excision of a cone of tissue
- May be complicated by burn artifacts
**LEEP**
- The use of a thin electric wire loop, which may have cutting and cautery currents
- Different sizes of loop and cautery tip available
- May be complicated by burn artifacts
32
Cervical cancer is the __ most common gynecology cancer in the US
- __ most common worldwide
Cervical cancer is the **3rd** most common gynecology cancer in the US (1. Uterine, 2. Ovarian)
- Decreasing incidence attributable to effective screening (1st)
Most common worldwide
33
When is high-risk HPV most common?
20-24 yo
34
What is the timeline for progressing from HPV to cancer?
About 20 yrs
35
What HPV types are most responsible for cervical cancer?
- type 16 (50%)
- type 18 (14%)
- type 31 (5%)
- type 45 (8%)
36
What are symptoms of cervical cancer?
- Postcoital, intermenstrual, or postmenopausal vaginal bleeding
- Persistent vaginal discharge
- More advanced cases:
* Pelvic pain
* Leg swelling
* Urinary frequency
37
What are physical findings of cervical cancer?
- Usually have normal general exam
- More advanced cases:
* Weight loss
* Enlarged LNs
* Edema of the legs
* Hepatomegaly
- Pelvic exam: ulcerative or exophytic lesions on cervix which can extend to vagina or pelvic side wall
38
What are the common histological types of cervical cancer?
- Squamous cell carcinomas (most common, 80%)
- Adenocarcinomas and adenosquamous carcinoma (20%)
- Melanomas and sarcomas are very rare
39
Describe the (Figo) stages of cervical cancer (0-IV)
**- Stage 0:** Carcinoma in situ, cervical intraepithelial neoplasia 3
**- Stage I**: The carcinoma is strictly confined to the cervix (extension to the corpus would be disregarded).
**- Stage II:** Cervical carcinoma invades to the uterus or beyond, but not to the pelvic wall or lower third of the vagina.
**- Stage III:** The carcinoma has extended to the pelvic wall.
* On rectal examination, there is no cancer-free space between the tumor and the pelvic wall.
* The tumor involves the lower third of the vagina.
* All cases with hydronephrosis or non-functioning kidney are included, unless they are known to be due to other causes
**- Stage IV**: The carcinoma has extended beyond the true pelvis, or has involved (biopsy-proven) the mucosa of the bladder or rectum.
40
Describe the 5 yr survival of cervical cancer by Figo stage?
- Stage I: 84%
- Stage II: 63%
- Stage III: 38%
- Stage IV: 12%
41
How to treat cervical cancer?
**- Early Stage I disease**: Usually treated with radical hysterectomy (don't do unless pretty sure you can get all the cancer out without leaving some behind)
**- Late Stage I disease and beyond**: Usually treated with chemoradiation and intracavitary brachytherapy
**- Recurrent or Metastatic Disease:**
* Chemotherapy is used but is not very effective
* If recurrent disease is localized in the pelvis, a pelvic exenteration can be done
42
What are the vaccination options for HPV?
**- Gardasil 9**- **Merck**: quadrivalent vaccine against HPV strains
* 6, 11, 16, 18, 31, 33, 45, 52, 58
**- Cervarix- GlaxoSmithKline**: bivalent vaccine against HPV strains:
* 16, 18
43
More on Gardasil 9?
- Protein contents
- How is it made
- Contains the L1 protein from nine types of HPV
- Produced using recombinant DNA technology
- L1 proteins self assemble into non-infectious units called virus-like particles (VLPs)
- VLPs are highly immunogenic
44
How efficacious is vaccination against HPV?
- High efficacy among females without evidence of infection with vaccine HPV types
- No evidence that the vaccine had efficacy against existing disease or infection
- Prior infection with 1 HPV type did not diminish the efficacy of the vaccine against other HPV types
45
What is the vaccine schedule for HPV?
- Approved for males and females 9-26 yo
- 3 doses at 0, 2, and 6 months
- Minimum intervals:
* 4 wks between doses 1 and 2
* 12 wks between doses 2 and 3
46
What are the recommendations for vaccination against HPV?
- Routine vaccination of males/females 11 or 12 years of age
- The vaccination series can be started as young as 9 years of age at the clinician's discretion
- Vaccination is recommended for females 13-26 years of age who have not been previously vaccinated
- Ideally vaccine should be administered before onset of sexual activity
- Adolescents who are sexually active should be vaccinated
47
Special situations: can you vaccinate females 26 or younger with equivocal or abnormal Pap test, positive HPV DNA, and genital warts?
Yes
- Vaccine will have no effect on existing disease or infection
48
Special situations: can you vaccinate females 26 or younger who are lactating/breastfeeding or are immunocompromised?
Yes
49
Special situations: can you vaccinate pregnant women
No!
50
How does cervical cancer screening differ for women who have had the HPV vaccine?
Screening does not change!
- 30% of cervical cancers caused by HPV types not prevented by the quadrivalent HPV vaccine
- Vaccinated females could subsequently be infected with non-vaccine HPV types
- Sexually active females could have been infected prior to vaccination
