Management Of Abnormal Pap Test, When To Refer For

ColposcopyAhmed Mousa MBBS, M.Sc, FRCSC, FACOG

Assistance Professor and Consultant of Gynecology Oncology

King Abdulaziz University

∗ The importance of cervical cancer screening ∗ The modality of screening∗ The advantages and the disadvantages of each

modality.∗ The interpretation of cytological abnormalities.∗ The management of of abnormal result.

Objectives

∗ Is the fourth most common cancer affecting women worldwide

∗ 528,000 cases estimated in 2012∗ 85% occur in developing countries

∗ 266,000 estimated death from cervical cancer ∗ account for 7.5% of all female cancer related death ∗ 87% of cervical cancer death occur in developing

countries.

GLOBOCAN 2012 (IARC)

Cervical Cancer

∗ Human Papillomavirus is the etiological risk factor ∗ Is the most common sexually transmitted disease with a

79% estimated life time risk of cervical infection. (CDC Fact sheet 2013)

∗ HPV DNA detected in 99.7% cervical carcinoma. (Walboomers, J.M., et al.)

Cervical Cancer Etiology

∗ HPV are classified based on their oncogenic characteristics into ∗ High risk type (oncogenic)

∗ HVP 16 & 18 account for 73% of cervical cancer cases.∗ HPV 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68 account

for the remaining cases

∗ Low risk type

Cervical Cancer Etiology

Woodman et al. Nature Reviews Cancer 7, 11–22 (January 2007) | doi:10.1038/nrc2050

HPV-mediated progression of cervical cancer

10 -13years 90% clear the infection within 2 years

∗ Pap test∗ Conventional ∗ Liquid based cytology

∗ HPV∗ Primary ∗ Reflex ∗ Co-testing

Screening for cervical cancer

∗ Since the introduction of Pap test as screening method, there has been 70% decreased in the incidence and mortality from cervical cancer

Pap test

∗ Conventional vs liquid based cytology ∗ Both have similar sensitivity and specificity for detection

high grade and low grade intraepithelial lesion ∗ conventional pap smear is more specific than LBC for

ASCUS∗ LBC reduces unsatisfactory pap test in subgroup of

patients with obscured blood and inflammatory cells.∗ LBC cytology offer the advantage of performing HPV

test

Pap test

Whitlock EP et al, Arbyn M et al, Davey E et all

∗ Overall the sensitivity of Pap test range between 50-70%

∗ Reasons for failure ∗ Failure to screen∗ Failure to detect abnormality in the first Pap test ∗ Failure to follow up abnormal Pap test

Pap test

Leyden et all, 2005

Solomon et al 2001

∗ hrHPV vs Pap test∗ Primary hrHPV or in combination with cytology is more

sensitive than pap test in the detection of HSIL and cancer.

∗ Use of hrHPV alone or in combination with cytology reduce the incidence of HSIL (RR:0.34 for primary and RR: 0.30 for cotetsting) and invasive cervical cancer (RR:0.44) compared to Pap test.

∗ Improved detection of ADK

HPV

∗ Role of genotyping ∗ HVP 16 and 18

∗ Cumulative incidence of HSIL over 3 years 21-26%

∗ Other types ∗ Cumulative incidence of HSIL over 3 years 5-6.5 %

HPV

∗ <21 ∗ No screening

∗ 21-29∗ Cytology alone every 3 years

∗ 30-65∗ HPV co-testing every 5 years ∗ Or cytology every 3 years

∗ >65∗ No screening unless

∗ Inadequate screening ∗ History of CIN 2/3, cervical ca

∗ Following Hysterectomy ∗ No screening following benign disease ∗ Screen if history of CIN 2/3, cervical cancer

Screening Per ASCCP 2012

Recently updated guideline for cervical cancer

Warner K. Huh , Kevin A. Ault , David Chelmow , Diane D. Davey , Robert A. Goulart , Francisco A.R. Garcia , Walte...

Use of primary high-risk human papillomavirus testing for cervical cancer screening: Interim clinical guidance

Gynecologic Oncology, Volume 136, Issue 2, 2015, 178 - 182

http://dx.doi.org/10.1016/j.ygyno.2014.12.022

∗ Defined as∗ Scanty cellularity ∗ Obscured by blood or inflammatory cells ∗ Or could not be processed for any reasons

Pap test should be repeated in 2-4 months∗ OR

∗ HPV negative repeat pap or HPV in 3 years ∗ HPV positive

∗ Colposcopy ∗ Or genotyping

∗ HPV 16/18 colpo∗ Other types

∗ Pap test ∗ Abnormal colop∗ Normal routine screen

Unsatisfactory

∗ HPV status ∗ Unknown

∗ Offer HPV test

∗ Positive ∗ Cytology and HPV at 1 year

∗ Negative routine screening

NILM but absent EC/TZ

∗ The most common abnormality (2.8%) ∗ Risk

∗ 7 % underlying CIN II∗ 3% underlying CIN III∗ 0.1% underlying invasive cancer

∗ 25% associated with HPV∗ HPV +

∗ 18% underlying CIN II∗ 7% underlying CIN III∗ 0.4% underlying invasive cancer

∗ HPV –∗ 1.5% underlying HSIL

∗ Options ∗ Repeat Pap test in one year

∗ ASCUS or more colpo∗ Normal routine screen

∗ Preform HPV (Reflex test)∗ Positive colpo∗ Negative routine screen

ASCUS

∗ Incidence 0.17%∗ Risk ∗ CIN II: 35%∗ CIN III: 18%∗ Invasive cancer: 2.6 %

∗ Patient must be referred to colposcopy ∗ Do not perform HPV ( 67% of patients are positive)

ASC-H

∗ Incidence 1 %∗ Risk

∗ CIN II:16%∗ CIN III: 5.2%∗ Invasive cancer :0.16%

∗ HPV + in 88%∗ HPV +

∗ CIN II: 19%∗ CIN III: 6%

∗ HPV negative∗ CIN II: 5%∗ CIN III : 2%

∗ Two options ∗ Colposcopy ∗ HPV

∗ Positive colposcopy ∗ Negative

∗ Repeat both test in one year ∗ If any abnormal colposcopy ∗ Normal routine screening

LSIL

∗ Incidence 0.21%∗ Risk ∗ CIN II: 70% ∗ CIN III: 47% ∗ Invasive cancer: 7%

∗ HPV positivity: 75%∗ Even those with negative test the risk of CIN II/III

>30% and invasive cancer 6% ∗ Refer to colposcopy

HSIL

∗ Incidence 0.1-2%∗ AGC

∗ Endocervical∗ Endometrial ∗ NOS

∗ 10% endometrial ca∗ AGC-favor neoplasia

∗ Endocervical∗ ADK 5%∗ AIS 2.5

∗ Endometrial ∗ Endometrial ca: 27% ∗ CAH: 22%

∗ NOS∗ AIS∗ Adenocarcinoma

∗ Finding is benign in 60-70%∗ Approximately 50% associated with squamous abnormality

AGC

∗ AGC-endometrial ∗ Perform endometrial biopsy and ECC∗ If negative refer to colposcopy

∗ AGC- other category∗ Colposcopy ∗ ECC∗ And endometrial biopsy if age > 35 and at risk of endometrial

ca∗ AIS

∗ Colposcopy ∗ If no lesion identified cold knife biopsy

AGC

Thank you