11/2- HPV and Cervical Cancer Flashcards
How are HPV infections classified?
High risk vs. low risk based on their oncogenic potential
Which strains of HPV are especially high-risk for cancer?
- Warts?
Cancer:
- 16, 18
- 31, 33
- many more
Warts:
- 6
- 11
- 40
- 42
- many more
What tissues does HPV infect?
HPV causes epithelial tumors of the skin and mucous membranes
- May be latent, subclinical…
Describe the structure of the HPV virus?
- Envelope?
- DNA vs. RNA
- Non-enveloped
- Double stranded circular DNA
How does HPV infect the cell?
- How does it spread?
- 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
T/F: HPV is the most common STD in the world
True
Female to male prevalence of HPV?
F > M (but only by about 1.4x)
What is the prognosis of HPV?
- 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
What is the original squamocolumnar junction?
Junction where the columnar epithelium meets the squamous epithelium on the ectocervix (at birth)
What happens regarding the jungtion during adolescence and pregnancy?
Metaplasia
- The junction of the columnar epithelium and the squamous epithelium moves proximally into the endocervix and is called the new squamocolumnar junction
What is the transformation zone?
The area between the original and the new squamocolumnar junction
What are the 2 types of screening?
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
High risk HPV has been implicated in __% of cervical cancers
High risk HPV has been implicated in 90% of cervical cancers
What can be use din conjunction with pap smears for cytology screening?
HPV genotype testing
How were these specimens collected?
Left: cytologic finding via pap smear
Right: histologic findings via cervical biopsy
Describe a colposcopy
- Binocular microscope with low magnification (10 to 40x) used to visualize the cervix;
- Usually prepared with acetic acid to help in identifying lesions
How can you obtain a cervical biopsy/endocervical curettage?
- Punch biopsy
- Scraping of endocervical cancal
What are the screening recommendations for HPV?
- < 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
What are risk factors for cervical dysplasia?
- 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
How to classify an abnormal pap smear (don’t have to memorize)?
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
What are the risks for different classifications proceeding to a worse stage/cancer?
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
Describe the appearance of cervical intraepithelial neoplasia
- 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)
What are the odds of CIN1-3 regressing, persisting, progressing to CIS, or invading?
How do you treat intraepithelial neoplasia?
- 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)
What are some ablative techniques?
- Cryotherapy
- Laser Vaporization therapy
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
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
What are excisional techniques for CIN?
Conization
- Cold Knife Cone
- Laser Conization
- LEEP (Loop Electrosurgical Excision Procedure)
Which techinque is preferred for CIS (Carcinoma in Situ where all the cells look abnormal)?
Cold Knife Zone
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
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
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
When is high-risk HPV most common?
20-24 yo
What is the timeline for progressing from HPV to cancer?
About 20 yrs
What HPV types are most responsible for cervical cancer?
- type 16 (50%)
- type 18 (14%)
- type 31 (5%)
- type 45 (8%)
What are symptoms of cervical cancer?
- Postcoital, intermenstrual, or postmenopausal vaginal bleeding
- Persistent vaginal discharge
- More advanced cases:
- Pelvic pain
- Leg swelling
- Urinary frequency
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
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
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.
Describe the 5 yr survival of cervical cancer by Figo stage?
- Stage I: 84%
- Stage II: 63%
- Stage III: 38%
- Stage IV: 12%
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
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
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
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
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
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
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
Special situations: can you vaccinate females 26 or younger who are lactating/breastfeeding or are immunocompromised?
Yes
Special situations: can you vaccinate pregnant women
No!
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
