- 2x doses given by IM injection at 0 and 5-13 months - If >15yo or immunocompromised then recommend 3x doses: 0, 2 and 6 months

Cervical Flashcards by Julia burcher

HPV % Cervical Cancer

99.7% of all cervical cancer

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High Risk HPV Strains

16 and 18 –> 70% of cervical cancer
6 and 11 –> genital warts (non-oncogenic)
31, 33, 45, 52 and 58 –> 19% of cervical cancer

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Other Cancers Associated with Oncogenic HPV

Vulva
 Vagina
Penis
 Anus 
Head and neck cancers

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HPV Vaccine Structure

Virus like proteins, DO NOT contain live, attenuated or killed virus

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Gardasil 9

contains all of the above list strains (6, 11, 16, 18, 31, 33, 45, 52, 58), therefore potentially prevents 90% cervical cancers

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NZ HPV Vaccination Program

Implemented in NZ 2008

Routine school based vaccinations in 1st year of high school (age 12-13) boys and girls

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Funded Gardasil 9

Age 9 -27 years

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Dosing Gardasil 9

2x doses given by IM injection at 0 and 5-13 months

- If >15yo or immunocompromised then recommend 3x doses: 0, 2 and 6 months

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Gardasil 9 Efficacy

Gardasil 9 efficacy 97%

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Testing for HrHPV

esting for high risk HPV has a strong negative predictive value (99%)

	§ Advantages:
		§ Better sensitivity of CIN2/3
		§ Higher negative predictive value of a negative test
		§ Avoids unnecessary interventions
	§ This can be done only on liquid based cytology
	§ Useful for LSIL/ASCUS >30yo --> if positive refer for colp, if negative then repeat in 12months
	§ Also useful for follow up:
		§ Following treatment for CIN2/3 doe HrHPV at 12month cytology
			□ Continue annually until both cytology and hrHPV are negative on 2 consecutive samples, then can be routine 3 yearly
			□ hrHPV takes 12months to clear so no point doing it sooner after treatment

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NZ Cervical Screening Population

Women age 20-69yo who have ever been sexually active

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Frequency of Cervical Screening

3yearly unless

first smear : repeat 1 year
last smear >5y ago : repeat 1 year

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Cervical Screening in NZ

50% who die from cervical Ca never been screened
In NZ since 1990 , rates reduced by 60%
Gap between Maori and non Maori

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Cervical Screening Post Hysterectomy

Women who need smears after hysterectomy:

- If the hysterectomy was subtotal
- If the hysterectomy was for CIN 2/3/ACIS and complete excision (need annual vault smear for 5 years then routine 3yrly)
- If previous CIN/2/3 on smears previous treated and normalised probably due routine vault smears
- If previous invasive gynaecological malignancy (at discretion of gynaeoncologist)
- If previous VAIN (1-2yearly smears)
- If immunosuppressed - routine 3yearly vault smears
- DES exposure - 1-2yearly vault smear and vaginal wall palpation - If smear history is not known then take smear at time of hysterectomy and if normal then no smears needed.

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WHO Principles of Screening

The condition should be an important health problem
1. There should be a treatment for the condition
2. Facilities for diagnosis and treatment should be available.
3. There should be a latent phase of the disease
4. There should be a test or examination for the condition
5. The test should be acceptable to the population
6. The natural history of the disease should be well understood
7. There should be an agreed policy on who to treat
8. The total cost of finding a case should be economically balanced with medical expenditure as a whole
  Case-finding should be a continuous process not a once and for all project.

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Staging

Stage I to IV

Subgrouped

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Stage I

The carcinoma is strictly confined to the cervix (extension to the uterine corpus should be disregarded)

Stage IA

Invasive carcinoma that can be diagnosed only by microscopy, with maximum depth of invasion <5mm

IA1

Measured stromal invasion <3mm in depth

IA2

Measured stromal invasion ≥3mm and <5mm in depth

Stage IB

Invasive carcinoma with measured deepest invasion ≥5mm (greater than Stage IA), lesion limited to the cervix uteri

IB1

Invasive carcinoma ≥5mm depth of stromal invasion, and <2cm in greatest dimension

IB2

Invasive carcinoma ≥2cm and <4cm in greatest dimension

IB3

Invasive carcinoma ≥4cm in greatest dimension

Stage II

The carcinoma invades beyond the uterus, but has not extended onto the lower third of the vagina or to the pelvic wall

Stage IIA

IIA

Involvement limited to the upper two‐thirds of the vagina without parametrial involvement

IIA1

Invasive carcinoma <4cm in greatest dimension

IIA2

Invasive carcinoma ≥4cm in greatest dimension

Stage IIB

IIB

With parametrial involvement but not up to the pelvic wall

Stage III

The carcinoma involves the lower third of the vagina and/or extends to the pelvic wall and/or causes hydronephrosis or nonfunctioning kidney and/or involves pelvic and/or para‐aortic lymph node

Stage IIIA

The carcinoma involves the lower third of the vagina, with no extension to the pelvic wall

Stage IIIB

Extension to the pelvic wall and/or hydronephrosis or nonfunctioning kidney (unless known to be due to another cause)

Stage IIIC

IIIC Involvement of pelvic and/or para‐aortic lymph nodes, irrespective of tumor size and extent (with r and p notations)c IIIC1 Pelvic lymph node metastasis only IIIC2 Para‐aortic lymph node metastasis

Stage IV

The carcinoma has extended beyond the true pelvis or has involved (biopsy proven) the mucosa of the bladder or rectum. (A bullous edema, as such, does not permit a case to be allotted to Stage IV)

Stage IVA

Spread to adjacent pelvic organs

Stage IVB

Spread to distant organs

Histopathologic Types

1. Squamous cell carcinoma (keratinizing; non‐keratinizing; papillary, basaloid, warty, verrucous, squamotransitional, lymphoepithelioma‐like) 2. Adenocarcinoma (endocervical; mucinous, villoglandular, endometrioid) 3. Clear cell adenocarcinoma 4. Serous carcinoma 5. Adenosquamous carcinoma 6. Glassy cell carcinoma 7. Adenoid cystic carcinoma 8. Adenoid basal carcinoma 9. Small cell carcinoma 10. Undifferentiated carcinoma

Histopathological Grades

GX: Grade cannot be assessed G1: Well differentiated G2: Moderately differentiated G3: Poorly or undifferentiated

Stages of Cervical Cancer Development

1. Oncogenic HPV infection of the metaplastic epithelium of the transformation zone 2. Persistence of HPV infection 3. Progression of a clone of epithelial cells from persistent viral infection to pre-cancer 4. Development of carcinoma and invasion through the basement membrane

Histologic % of Cervical Cancer

- Squamous cell carcinoma 69% - Adenocarcinoma 25% - Other 6% ○ (clear cell, serous, adenosquamous, adenoid, small cell…)

Lymphatic Drainage

``` ○ External iliac (43%) ○ Obturator (26%) ○ Parametrial (21%) ○ Common iliac ○ Presacral ○Para-aortic ```

Treatment Stage IA1

Cone or LLETZ with adequate margin, or simple hysterectomy

Treatment Stage IA2 to IB1

Cone + lymphadenectomy or simple hysterectomy + LND (if fertility not desired). Traditionally managed with radical hysterectomy and LND

Treatment Stage IB2

Radical hysterectomy + PLND + Combined chemo and radical radiation therapy (external beam and brachytherapy) --> Or experimental fertility sparing is neoadjuvant chemo + Cone

Treatment Stage IB3 - IVA

Radical Hysterectomy + combined chemo and radiotherapy

Treatment Stage IVB

Chemo +/- antiangiogenesis agent (Abastin/bevacizumab) | *NB no rad hyst for stage above IVA

Simple Hysterectomy

Indication- 1A1-1B1 Uterus and cervix- Removed Vaginal margin- none Ureters-Not mobilised Cardinal ligaments- Divided at uterine and cervical border Uterosacral ligament-Divided at cervical border Bladder-Divided to base of bladder Rectum- Not mobilised Surgical approach-Any

Radical Hysterectomy

Indication - 1B2 -4A Uterus and cervix - Removed Vaginal margin - Upper 1/4 to 1/3 Ureters - Tunnelled through broad ligament Cardinal Ligaments- Divided at pelvic side wall Uterosacral Ligaments - Divided at sacral origin Bladder - Mobilised to mid vagina Rectum- Mobilised below the cervix Approach - Any