Current guidelines for Cervical Cancer Screening

Rachael Chambers, DO

May 29, 2015

Objectives

• Review current cervical cancer screening guidelines

• Discuss role of HPV testing in cervical cancer screening

• Discuss role of primary HPV testing in cervical cancer screening

Background

• Initial Bethesda system classification – revised in 2001

• ASCCP consensus conference 2006• Updated guidelines in 2008

– Not from a national consensus conference

• 2012 follow up consensus conference– Data from KPNC, NCI, ALTS

2012 Consensus Conference

• 47 experts • 23 professional societies• Goal to provide revised evidence-based

consensus guidelines for managing women with abnormal cervical cancer screening tests, cervical intraepithelial neoplasia and adenocarcinoma in-situ

Major changes 2012 guidelines

• ECC showing CIN 1 – manage as CIN 1

• Repeat unsatisfactory cytology– Even when HPV results are known

• Negative cytology with absent or insufficient endocervical cells can be managed without early repeat

Major changes 2012 guidelines

• Genotyping triages HR HPV positive women to colposcopy earlier after negative cytology– Colposcopy indicated for ASCUS +HPV

regardless of genotyping

• HPV negative ASCUS– Follow up at 3 years with co-testing

– Not sufficient for exiting women from screening at age 65

Major changes 2012 guidelines

• CIN 2+ follow up is more clearly defined with incorporation of co-testing

• Women age 21-24– Conservative management

– Pap only

– Co-test in certain circumstances

• Incorporate co-testing post colposcopy

Guidelines

• Available at:• www.asccp.org/Portals/9/docs/ASCCP%20Mana

gement%20Guidelines_August%202014.pdf

• App available for iPad, iPhone and Android

Routine Screening

• Cytology every 3 years• Co-testing every 5 years

– Women age 30-64 only

• Multi-year intervals ok only if risk of developing CIN 3+ is low

Case 1

• 55 year old G2P2• Menopause at age 52• No history of abnormal pap testing• Pap test with physical shows:

– Insufficient cellularity. HPV co-testing is negative.

• Now what?

Unsatisfactory Cytology

• 1% or less across all preparations• Decreased with use of liquid based pap• Most cases now due to insufficient squamous

cells

Case 2

• Same patient as in Case 1• Now pap test shows normal results, but no

EC/TZ• HPV remains negative

• Now what?

Cytology NILM but EC/TZ Absent/Insufficient

• Suggests squamocolumnar junction may not have been adequately sampled

• Reported rates 10-20%• More prevalent in older women• Good specificity and negative predictive value• HPV testing is independent of TZ sampling

– Adds margin of safety when co-testing is performed.

Management

• Age 21-29: routine screening• Age 30-64

– HPV negative: Routine screening

– HPV unknown: Test for HPV or repeat cytology in 3 years

– HPV positive: Cytology +HPV in 1 year or HPV genotyping

Case 3

• 32 year old G1P0• No previous pap testing available• Here for initial prenatal care• How do we screen her?

Case 3 continued

• Pap test normal• HPV co-test is positive

• Now what?

Management Negative Cytology, HPV positive

• Due to increased risk for CIN 3+ if hrHPV positive guidelines balance risk of observation vs intervention

• Return for earlier retesting• HPV genotyping

– Higher risk of CIN 3+ with type 16/18

• Colposcopy if 1 year follow up is ASC or HPV + or immediately if HPV 16/18 are positive

Case 4

• 30 year old referred to you for management of ASCUS pap

• What else do you want to know?

• Was she HPV co-tested?

Atypical Squamous Cells of Undetermined Significance

• Most common cytologic abnormality• Lowest risk of CIN 3+

– 2/3 are NOT HPV associated

• Women >60 years have higher risk for cervical cancer even if HPV negative compared to women with negative co-testing.

ASC-US

• Reflex HPV testing preferred– Type 16/18 positive women have twice the risk of

CIN 3+ compared to other hrHPV positive women

• HPV negative– Repeat cotesting in 3 years

• HPV positive– Colposcopy

– If no CIN co-test at 12 months

ASC-US

• Cytology only– Repeat cytology in 1 year

– Colposcopy if > ASC

– Routine screening if normal

ASC-US in Special Populations

• Postmenopausal– Manage the same as general population

• Women age 65 and older– Repeat screening in 1 year when considering exit

from screening• Cytology• Co-testing (preferred)

ASC-US in Special Populations

• Pregnant women– Identical to nonpregnant women

– Acceptable to defer colposcopy until 6 weeks postpartum

– ECC is unacceptable

– If no suspected CIN 2+ at initial colposcopy, follow up postpartum

Case 5

• 21 year old, G0• No previous pap test• Seen for complete physical• Pap test shows LSIL.

• What next?

Young Women

• No screening before age 21• Routine screening with initial normal pap test is

every 3 years– Cervical CA risk is low through age 25

– HPV is common

– Most lesions will regress

• Less intensive management• Encourage HPV vaccination, smoking cessation

Young women

• ASCUS/LSIL Cytology every 12 months preferred– HPV reflex is acceptable

• Follow up is repeat cytology if positive• Routine screening if negative

• Colposcopy only if ASC-H, AGC, HSIL at follow up

Low-grade Squamous Intraepithelial Lesions

• ALTS Trial showed natural history to be similar to ASC-US HPV+

• Women 21-24 have lower risk CIN 3+• Estimated 77% of LSIL are HPV positive

LSIL Management

• Colposcopy (recommended)– Manage based on colposcopic findings

• If co-test is negative, repeat co-test in 1 year– If cytology negative and HPV negative

• Repeat co-testing in 3 years

– If >ASC or HPV positive• Colposcopy

LSIL Management

• Pregnant women: – Colposcopy preferred

• ECC unacceptable• Acceptable to defer until 6 weeks postpartum

– If no CIN 2+, follow up post partum

LSIL Management

• Postmenopausal– Obtain HPV test

– Repeat cytology at 6 and 12 months

– Colposcopy

– Repeat cytology in 12 months if HPV negative or no CIN on colposcopy

– If HPV+ or ASC-US or greater on repeat cytology perform colposcopy

– Routine screening after 2 negative cytology

Atypical Squamous Cells, Cannot Exclude High-Grade

Squamous Intraepithelial Lesion• Higher risk of CIN 3+ compared to ASC-US or

LSIL– Risk also elevated for women age 21-24, but

overall CIN 3+ risk remains lower than older women

ASC-H Management

• Colposcopy for all women• High rate of HPV + makes reflex testing

unsuitable• 5 year cancer risk among ASC-H, HPV negative

is 2%

High-Grade Squamous Intraepithelial Lesion

• CIN 2+ identified in 60% of women at colposcopy

• Consider immediate excision of transformation zone

• Cervical cancer found in 2% at colposcopy– Risk rises with age

– Risk modifies with HPV result

• HPV result from co-test may help inform choice

Management HSIL

• Immediate LEEP• Colposcopy

– Diagnostic excisional procedure recommneded for inadequate colposcopy

• Except if pregnant

HSIL in Young Women

• Colposcopy– If no CIN 2+ observe with colposcopy and

cytology at 6 month intervals for 24 months.

– If CIN 2/3 present manage with colposcopy and biopsy or treat

Atypical Glandular Cells

• Interpretation is poorly reproducible and uncommon

• Associated with – Polyps – Metaplasia– Neoplasia

• Adenocarcinomas– Endometrium, cervix, ovary, fallopian tube and other

sites

AGC

• Risk of neoplasia higher if reported as AGC favor neoplasia or AIS

• Cancer risk is lower in women <35, but risk of CIN 2+ is higher

• Commonly associated with squamous lesions including CIN 1

AGC Management

• Colposcopy with ECC• Do not use HPV testing to triage• Endometrial sampling is recommended in

women 35+– Also for women <35 if clinical indictors suggesting

risk for endometrial neoplasia.

• If no CIN 2+ co-test at 12 and 24 months and routine screening if both are negative.

PRIMARY HPV SCREENING

What’s next?

Primary hrHPV screening

• Rate of hrHPV is common in sexually active population

• Most infections are transient• FDA previously approved hrHPV testing

– For triage of ASCUS

– Adjunct to cytology for women age 30+

• April 2014 FDA approved labeling of hrHPV assay to include primary hrHPV screening in women 25+

Primary hrHPV screening

• Highly sensitive• Specificity depends on subsequent evaluation

strategies and screening frequencies

2011 guidelines

• American Cancer Society, American Society for Colposcopy and Cervical Pathology and American Society for Clinical Pathology

• “in most clinical settings, women age 30-65 should not be screened with HPV testing alone as an alternative to co-testing at 5 year intervals or cytology alone at 3 year intervals”

Consensus panel

• Met via conference call and face to face• Invited to scientific summary presentation by

Roche Diagnostics of the Addressing the Need for Advanced HPV Diagnostics (ATHENA) trial

• MEDLINE database review– 11 papers reviewed in addition to significant

papers published prior to November 2011

Consensus panel: Primary question

• Is hrHPV testing for primary screening as safe and effective as cytology-based screening?

• Negative hrHPV provides greater reassurance of low CIN3+ risk than negative cytology.– Several large trials have evaluated this

Consensus panel: Primary question

• Can primary hrHPV screening be considered as an alternative to current US cervical cancer screening methods?

• hrHPV can be considered as an alternative to current cytology-based screening because of equivalent of superior effectiveness.

Additional questions

• How Should Positive hrHPV be managed?– Combination of triage of genotyping and reflex

cytology appears to be a reasonable approach• Based on data from ATHENA and other studies

• What is the Optimal Screening interval?– No sooner than every 3 years

• Limited data available

Additional questions

• At What Age Should One initiate primary HPV screening?– Not before age 25

Additional questions

• How does the performance of primary hrHPV screening compare to co-testing?– Most reassurance from co-test comes from the

HPV component.

– Data shows the 3 year risk following HPV negative test is less than the 5 year risk following co-testing.

– Primary hrHPV test every 3 years is at least as effective as 5 year co-testing.

• Currently only 1 hrHPV test is FDA-approved for primary screening.

• Comparative effectiveness studies are needed • Look for future updates

Summary

• Cervical cancer screening continues to evolve.• Trend is toward less invasive methods of

screening and managing.• hrHPV screening may become the primary

screening tool in the future.

References

• Massad, et al. 2012 Updated Consensus Guidelines for the Management of Abnormal Cervical Cancer Screening Tests and Cancer Precursors. Journal of Lower Genital Tract Disease, Volume 17, Number 5, 2013, S1-S27.

• Huh , et al. Use of Primary High-Risk Human Papillomavirus Testing for Cervical Cancer Screening: Interim Clinical Guidance. Journal of Lower Genital Tract Disease, Volume 19, Number 2, 2015, 91-96.

• Partridge et al. Cervical Cancer Screening: Featured Updates. Journal of the National Comprehensive Cancer Network. Volume 12, number 3, march 2014, 333-341.

• ACOG Practice Bulletin. Management of Abnormal Cervical Cancer Screening Test Results and Cervical Cancer Precursors. Number 140, Volume 122, No. 6, December 2013, 1338-1367

• Saraiya, et al. Evolution of cervical cancer screening and prevention in United States and Canada: Implications for public health practitioners and clinicians. Preventive Medicine, Volume 57, 2013, 426-433.

• Dinkelspiel and Kinney. State of the Science: Cervical cancer screening in transition. Gynecologic Oncology, 133, 2014, 389-393.

• Cannistra and Niolff. Cancer of the Uterine Cervix. The New England Journal of Medicine. Volume 334, number 16, 1996, 1030-1038.