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?
- 16, 18
- 31, 33
- many more
- 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?
- DNA vs. RNA
- 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
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?
- 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
- Cervical cell sample put into liquid medium for suspension before automated thin layer/monolayer slide preparation
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
- Immunosuppressed status
- 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)
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?
- Laser Vaporization therapy
- 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?
- 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
- 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