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a_GYNGU > 11/2- HPV and Cervical Cancer > Flashcards

11/2- HPV and Cervical Cancer Flashcards

1
Q

How are HPV infections classified?

A

High risk vs. low risk based on their oncogenic potential

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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
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3
Q

What tissues does HPV infect?

A

HPV causes epithelial tumors of the skin and mucous membranes

  • May be latent, subclinical…
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4
Q

Describe the structure of the HPV virus?

  • Envelope?
  • DNA vs. RNA
A
  • Non-enveloped
  • Double stranded circular DNA
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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
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6
Q

T/F: HPV is the most common STD in the world

A

True

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7
Q

Female to male prevalence of HPV?

A

F > M (but only by about 1.4x)

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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
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9
Q

What is the original squamocolumnar junction?

A

Junction where the columnar epithelium meets the squamous epithelium on the ectocervix (at birth)

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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
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11
Q

What is the transformation zone?

A

The area between the original and the new squamocolumnar junction

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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
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13
Q

High risk HPV has been implicated in __% of cervical cancers

A

High risk HPV has been implicated in 90% of cervical cancers

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14
Q

What can be use din conjunction with pap smears for cytology screening?

A

HPV genotype testing

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15
Q

How were these specimens collected?

A

Left: cytologic finding via pap smear

Right: histologic findings via cervical biopsy

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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
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17
Q

How can you obtain a cervical biopsy/endocervical curettage?

A
  • Punch biopsy
  • Scraping of endocervical cancal
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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
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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
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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
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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
Q

What are some ablative techniques?

A
  • Cryotherapy
  • Laser Vaporization therapy
26
Q

Describe cryotherapy

A
  • 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
Q

Describe laser vaporization therapy

A
  • The use of a laser to vaporize the transformation zone containing the lesion
  • Requires suction to remove smoke
  • Different power levels are available
28
Q

What are excisional techniques for CIN?

A

Conization

  • Cold Knife Cone
  • Laser Conization
  • LEEP (Loop Electrosurgical Excision Procedure)
29
Q

Which techinque is preferred for CIS (Carcinoma in Situ where all the cells look abnormal)?

A

Cold Knife Zone

30
Q

Describe Conization

A

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
Q

Describe the subtypes of conization:

  • Cold Knife Cone
  • Laser Conization
  • LEEP (Loop Electrosurgical Excision Procedure)
A

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
Q

Cervical cancer is the __ most common gynecology cancer in the US

  • __ most common worldwide
A

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
Q

When is high-risk HPV most common?

A

20-24 yo

34
Q

What is the timeline for progressing from HPV to cancer?

A

About 20 yrs

35
Q

What HPV types are most responsible for cervical cancer?

A
  • type 16 (50%)
  • type 18 (14%)
  • type 31 (5%)
  • type 45 (8%)
36
Q

What are symptoms of cervical cancer?

A
  • Postcoital, intermenstrual, or postmenopausal vaginal bleeding
  • Persistent vaginal discharge
  • More advanced cases:
  • Pelvic pain
  • Leg swelling
  • Urinary frequency
37
Q

What are physical findings of cervical cancer?

A
  • 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
Q

What are the common histological types of cervical cancer?

A
  • Squamous cell carcinomas (most common, 80%)
  • Adenocarcinomas and adenosquamous carcinoma (20%)
  • Melanomas and sarcomas are very rare
39
Q

Describe the (Figo) stages of cervical cancer (0-IV)

A

- 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
Q

Describe the 5 yr survival of cervical cancer by Figo stage?

A
  • Stage I: 84%
  • Stage II: 63%
  • Stage III: 38%
  • Stage IV: 12%
41
Q

How to treat cervical cancer?

A

- 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
Q

What are the vaccination options for HPV?

A

- 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
Q

More on Gardasil 9?

  • Protein contents
  • How is it made
A
  • 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
Q

How efficacious is vaccination against HPV?

A
  • 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
Q

What is the vaccine schedule for HPV?

A
  • 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
Q

What are the recommendations for vaccination against HPV?

A
  • 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
Q

Special situations: can you vaccinate females 26 or younger with equivocal or abnormal Pap test, positive HPV DNA, and genital warts?

A

Yes

  • Vaccine will have no effect on existing disease or infection
48
Q

Special situations: can you vaccinate females 26 or younger who are lactating/breastfeeding or are immunocompromised?

A

Yes

49
Q

Special situations: can you vaccinate pregnant women

A

No!

50
Q

How does cervical cancer screening differ for women who have had the HPV vaccine?

A

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

a_GYNGU (17 decks)

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