INTRAEPITHELIAL NEOPLASIA OF THE LOWER

GENITAL TRACT (CERVIX, VAGINA, VULVA)

Etiology, Screening, Diagnosis, Management

REPORTER: ALDILYN J. SARAJAN MD, MPH

3RD YEAR OB-GYNE RESIDENT
Etiology: HUMAN PAPILLOMAVIRUS

• Most common sexually transmitted disease

• HPV is a double-stranded DNA virus

▫ HPV 16 and 18
 Risk Factors
Early onset of sexual activity

Multiple sexual partners

History of sexually transmitted infection

Oral contraceptive use

History of vulvar or vaginal dysplasia

Primary prevention: Vaccination
• Bivalent vaccine (cervarix)
▫ HPV types 16, 18

• Quadrivalent vaccine (gardasil)

▫ HPV types 16, 18, 6, 11

• Nonvalent vaccine (gardasil-9)

▫ HPV types 16, 18, 6, 11,, 31, 33, 45, 52, and 58
Secondary prevention: TESTING
1. CERVICAL CYTOLOGY TESTING (PAP TEST)
Secondary prevention: TESTING
2. PRIMARY HUMAN PAPILLOMAVIRUS
TESTING

• More sensitive
• Preferred screening method in countries where
Pap testing is not feasible (WHO, 2015)
Cervical cancer screening guidelines
 CERVICAL CYTOLOGY REPORTING: THE
BETHESDA SYSTEM
• Satisfactory or unsatisfactory
▫ Unsatisfactory
 lack of a label, loss of transport medium, scant
cellularity, and contamination by foreign material

• Cellular material
ATYPICAL SQUAMOUS CELLS (ASC) OF UNDETERMINED SIGNIFICANCE (ASC-
US)

• Most common squamous abnormality

ATYPICAL SQUAMOUS CELLS, CANNOT EXCLUDE A HIGHER-GRADE LESION

• Evaluated with colposcopy, higher likelihood

that CIN 2/3 is present
LOW-GRADE SQUAMOUS INTRAEPITHELIAL
LESION
• Low-grade dysplasia or cervical intraepithelial
neoplasia 1
HIGH-GRADE SQUAMOUS INTRAEPITHELIAL
LESION
• Indicates more severe dysplasia or CIN 2/3
 ATYPICAL GLANDULAR CELLS
• 3 out of every 1000 pap tests

• Risk of underlying invasive cancer is 3% to 17%

• Colposcopy with endocervical sampling

• Endometrial sampling should be performed in

women who are older than 35 years or at risk for
endometrial cancer
 COLPOSCOPY
• First step in evaluation of women with abnormal cytology
Colposcope
• The instrument is placed just outside the vagina after a
speculum has been inserted and the cervix brought into
view.
• After any obscuring mucus is removed with a swab, the
cervix is carefully examined for the presence of lesions.
• Dilute acetic acid (3% to 5%) is applied to the cervix, and
after 30 to 60 seconds the cervix is again examined.
• Acetic acid dehydrates the epithelial cells and dysplastic
cells with large nuclei will reflect light and appear white.
 COLPOSCOPY
• Endocervical curettage (ECC):
▫ abnormal cytology / unsatisfactory

• Cervical biopsies:
▫ any acetowhite lesions

• Ferric subsulfate (monsel’s solution) or silver

nitrate sticks:
▫ control bleeding
 CERVICAL DYSPLASIA IN PREGNANCY
• Colposcopy is safe in pregnancy

• Biopsies should only be performed for invasive

disease

• Evaluation: 6 to 8 weeks after delivery

• ECC should never be performed

 CERVICAL DYSPLASIA IN PREGNANCY
• CIN2/3: delayed until the postpartum period

• Dysplastic lesion, a follow-up with colposcopy or

repeat cytology at intervals no more frequent
than every 12 weeks

• Invasive cancer: conization procedure under

anesthesia can be performed
 NATURAL HISTORY OF CERVICAL
INTRAEPITHELIAL NEOPLASIA
• Cervical intraepithelial neoplasia (CIN):
▫ precancerous lesion of the squamous epithelium
of the cervix
 NATURAL HISTORY OF CERVICAL
INTRAEPITHELIAL NEOPLASIA
• CIN 1, or mild dysplasia
▫ frequently spontaneously regresses, often within weeks to
months.
• CIN 2:
▫ cellular atypia involves two thirds of the thickness of the
epithelium; 40% regressing spontaneously without
treatment
• CIN 3 (severe dysplasia and carcinoma in situ):
▫ the cellular atypia involves more than two thirds of the
epithelium; a precursor to invasive cancer, and treatment is
recommended; one third of these lesions may spontaneously
disappear
CERVICAL INTRAEPITHELIAL NEOPLASIA 1
CERVICAL INTRAEPITHELIAL NEOPLASIA 1
CERVICAL INTRAEPITHELIAL NEOPLASIA 1
CERVICAL INTRAEPITHELIAL NEOPLASIA 2/3
CERVICAL INTRAEPITHELIAL NEOPLASIA 2/3
 TREATMENT OF CERVICAL DYSPLASIA
• Treatment of CIN can be accomplished by

▫ Ablation
 Cryotherapy
 CO2 laser ablation.

▫ Excision
 Loop electrosurgical excision procedure (LEEP)
 Cold knife conization (CKC)
 CO2 laser conization.
 Ablative Methods
• Satisfactory colposcopy with visualization of
entire cervical squamocolumnar junction

• Biopsy confirmingpresence of CIN; abnormal

cytology alone is not sufficient

• Lesion does not involve the endocervical canal

and negative endocervical curettage (if
available)
 Ablative Methods: Cryotherapy
• safe, effective, and relatively simple to perform.
X Contraindications:
• Large lesions (those covering
>75% of the cervix or those
that cannot be covered by the
cryoprobe)
• Lesions that extend into the
endocervical canal
• Endocervical curettage
performed and it shows
evidence of dysplasia
 Ablative Methods: Cryotherapy
• Includes colposcopy

• N2O: refrigerant

• 3-5-3 double freeze–thaw cycle is performed

with 3 minutes of freezing, followed by 5
minutes of thawing and another 3 minutes of
freezing.
Ablative Methods: CO2 Laser Ablation
• A focused CO2 laser beam is directed at the
cervical epithelium, where water in the tissue
absorbs the laser energy and the tissue is
destroyed by vaporization.

▫ The lesion is typically ablated to a depth of 5 mm

• The advantages of this technique

▫ The area of can be minimize tissue destruction and
no prolonged vaginal discharge
 Excisional Methods
• The specific indications include the following:
 Suspected microinvasion
 Adenocarcinoma in situ or other glandular abnormalities
 Unsatisfactory colposcopy in which the transformation zone is
not fully visualized
 Lack of correlation between cytology and colposcopy/biopsies
 Unable to rule out invasive disease
 Lesion extending into the endocervical canal
 Endocervical curettage showing CIN or a glandular
abnormality
 Recurrence after an ablative or previous excisional procedure
Excisional Methods: Loop Electrosurgical
Excision (LEEP)
• Is currently the most common method for the
treatment of CIN 2/3

• Removal of the transformation zone of the cervix

under local anesthesia.
Excisional Methods: Loop Electrosurgical
Excision (LEEP)

• The removed tissue is examined histologically

for diagnosis and evaluation of margin status.

• Management guidelines for positive margins are

provided by the ASCCP and include re-excision
versus follow-up cytology and endocervical
sampling, depending on pathology results,
patient age, and the desire for future fertility. 25
 Excisional Methods:
Cold Knife Conization
• an excisional procedure similar to a LEEP but is
performed with a scalpel under anesthesia in the
operating room.
 FOLLOW-UP AFTER TREATMENT OF
CERVICAL DYSPLASIA

• Factors associated with recurrent/persistent

disease include the following:

▫ Large lesion size

▫ Endocervical gland involvement
▫ Positive margins
 CERVICAL CANCER PREVENTION IN
LOWAND MIDDLE-INCOME COUNTRIES

• Visual Inspection with Acetic acid (VIA)

▫ acetic acid is applied to the cervix
 VAGINAL INTRAEPITHELIAL NEOPLASIA
(VaIN)
• Similar to CIN

• Squamous atypia without invasion.

• Incidence: unknown
▫ estimated to be approximately 0.2/100,000 in the
United States.

• Common between 43 to 60 years of age.

 VAGINAL INTRAEPITHELIAL NEOPLASIA
(VaIN)
• Risk factors
▫ current or previous neoplasia elsewhere in lower genital
tract (cervix, vulva)
▫ persistent HPV infection

• VaIN 1: surveillance
• VaIN 2 or VaIN 3: treatment,
▫ risk of progression to vaginal cancer is 2% to 5%
• Treatment:
▫ excision, ablation, and topical therapy with 5-
fluorouracil or imiquimod
 VULVAR INTRAEPITHELIAL NEOPLASIA
(VIN)
• Squamous atypia of the vulva

• incidence of VIN 3 :2.86 per 100,000 women

 VULVAR INTRAEPITHELIAL NEOPLASIA
(VIN)
• classified as
1. VIN, usual type
 Most common form
 HPV associated condition
 younger women, may be multifocal, and is associated with
cervical and vaginal dysplasia

2. VIN, differentiated type

 less common
 unrelated to HPV infection,
 associated with chronic inflammatory conditions
 lichen sclerosus and lichen planus.
 VULVAR INTRAEPITHELIAL NEOPLASIA
(VIN)
• Symptoms
▫ pruritus, pain, and burning

• Punch biopsies
▫ any lesions noted on the vulva
 VULVAR INTRAEPITHELIAL NEOPLASIA
(VIN)
• Symptoms
▫ pruritus, pain, and burning

• Punch biopsies
▫ any lesions noted on the vulva

• Colposcopy of the vulva (vulvoscopy) with

biopsies of any lesions
▫ in all patients with CIN or VaIN
 VULVAR INTRAEPITHELIAL NEOPLASIA
(VIN)
• VIN 1
▫ benign entity, and treatment for asymptomatic
disease is not necessary
• VIN 2/3
▫ Undergo treatment
▫ Treatment: excision, ablation, and topical
therapies
▫ with underlying invasive disease: wide local
excision
 VULVAR INTRAEPITHELIAL NEOPLASIA
(VIN)
• Diffuse disease:
▫ CO2 laser ablation and topical therapies

• most commonly used topical therapy

▫ Imiquimod

• no standard guidelines for the follow-up of

patients with VIN 2/3: vulvoscopy every 6 to 12
months for 2 years
THANK
YOU 