Update on HPV Testing Robert Schlaberg, M.D., Dr. med., M.P.H. - - PowerPoint PPT Presentation

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Update on HPV Testing Robert Schlaberg, M.D., Dr. med., M.P.H. - - PowerPoint PPT Presentation

Apr 11, 2024 612 likes •992 views

Update on HPV Testing Robert Schlaberg, M.D., Dr. med., M.P.H. Assistant Professor, University of Utah Medical Director, ARUP Laboratories Disclosures In accordance with ACCME guidelines, any individual in a position to influence and/or control

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Update on HPV Testing

Robert Schlaberg, M.D., Dr. med., M.P.H. Assistant Professor, University of Utah Medical Director, ARUP Laboratories

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Disclosures

In accordance with ACCME guidelines, any individual in a position to influence and/or control the content of this ASCP CME activity has disclosed all relevant financial relationships within the past 12 months with commercial interests that provide products and/or services related to the content of this CME activity. Robert Schlaberg, MD, MPH has disclosed the following financial relationships with commercial interests: Commercial Interest What was Received For What Role Roche Diagnostics Honorarium Advisor Roche Diagnostics Research Grants PI Hologic Contract Research PI Hologic Honorarium Advisor Epoch Biosciences Contract Research PI Sanofi Pasteur Contract Research Co-PI IDbyDNA Stock Co-Founder, CMO

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Objectives

  • 1. Understanding the biology and epidemiology of HR HPV
  • 2. Understanding the performance of available cervical

cancer screening tests

  • 3. Reviewing recent changes to screening guidelines
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Background

Eva and Juan Perón

See: Lancet 2000; 355: 1988–91

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Cervical Cancer

  • Incidence

– Most frequent cancer death in women… now 14th – 12,000 cases, 4,200 deaths, 50% unscreened

  • Persistent HR HPV infection

– Almost 100% of cervical cancers HR HPV+ – HPV16 (55‐60%), HPV18 (10‐15%)

  • Cause all common/most rare histologic types

– Squamous cell carcinoma (80‐90%)

Am J Clin Pathol 2012;137:516‐542

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Cervical Cancer Trends ‐ US

2 4 6 8 10 12 14 16

1975 1977 1979 1981 1983 1985 1987 1989 1991 1993 1995 1997 1999 2001 2003 2005 2007 2009

Rate per 100,000

NCI, SEER 9, seer.cancer.gov

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Squamous Cervical Precursor Lesions

Modified from: J Clin Invest 2006;116:1167‐1173

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Degree of Dysplasia Regression (%) Persistence (%) Progression to CIN3 (%) Progression to Invasive Cancer (%) CIN I 57 32 11 1 CIN II 43 35 22 5 CIN III 32 56 N/A 12 to 50*

Natural History of Cervical Precancer

Lancet Oncol. 2008 May;9(5):425‐34 Lancet Oncol. 2008 May;9(5):404‐6 Int J Gynecol Pathol 1993; 12(2): 186‐92

* Untreated

CIN3 Invasion

Years 5 10 20 30 20 40 60 80 100

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HPV Infection

  • Most common viral STI
  • Incidence ~ 6 million/y; prevalence ~20 million
  • Lifetime risk ~ 50‐75%
  • Clearance 70% at 1 yr, 90% at 2 yrs

CDC, STD Surveillance, 2009

Progression

3

Clearance Persistence

Years 1 2 3 20 40 60 80 100

14‐19 20‐24 25‐29 30‐39 40‐49 50‐59

10 20 30 40 LR HPV HR HPV

Lancet Oncol. 2008 May;9(5):404‐6

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HPV Replication

J Clin Invest 2006;116:1167‐1173

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Role of HPV in Cervical Cancer

J Clin Invest 2006;116:1167‐1173

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HPV Biology

  • Double‐stranded, circular DNA, ~8kb
  • Oncogenes (E6, E7)
  • >100 types, >40 infect genital tract

– Low risk

6, 11, 42, 43, 44, 54, 61, 70, 72, 81

– Indeterminate risk – High risk

16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68

Fields Virology, 5th Edition Nature Reviews Cancer 6, 753‐763

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HPV Types – Association with Cancer

Fields Virology, 5th Edition Vaccine 24S3 (2006) S3/1‐S3/10

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HPV – Pathogenic Spectrum

  • LR HPV

– Genital warts, low‐grade cervical abnormalities – Recurrent respiratory papillomatosis

  • HR HPV

– Uterine cervix, vulva, vagina, anus, (penis) – Oropharynx (tonsil, base of tongue), esophagus

2000 4000 6000 8000 10000 12000 14000

Cases per year Male Female

MMWR 2012;61(15):258–261

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Clinical Science (2006) 110, 525‐541

LR HPV, selected HR HPV

  • I. Phylogeny

Challenges for HPV Tests I

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  • III. Analytical vs. Clinical Sensitivity

Challenges for HPV Tests III

Incident Cleared Persistent Progressing

HPV Testing Cytology Invasive Cancer

Normal

Measure of Risk Factor Measure of Disease

HPV Infection

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Clinical Cutoff For CIN2+

Am J Clin Pathol 2011;136:578‐586

Sensitivity ~ 90% for CIN2+ (pre‐defined) 40.5 (HPV16) 40.0 (HPV18) 40.0 (12 HR HPV)

Standard HPV Test New HPV Test Cytology Phase 1 (n ~ 29,000) Determine Clinical Cutoff Participants: Women age 21+, routine screening (n~45,000) 61 sites, 23 states, 2 cervical specimens Confirm Clinical Cutoff: Phase 2 participants (n ~ 18,000) Determine clinical performance

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Screening

Harald zur Hausen Georgios Papanikolaou

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Cervical Cancer Screening

  • Pap test

– Identifies dysplasia / pre‐cancer / cancer – High specificity

  • HPV test

– Identifies women at risk – High negative predictive value (CIN, cancer) – Higher reproducibility

  • Combined

– ASCUS‐triage: follow‐up interval (≥21y) – Co‐testing with cytology (≥30y)

Ann Intern Med 132 (10): 810‐9 Am J Clin Pathol 2012;137:516

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http://www.cdc.gov/cancer/cervical/pdf/guidelines.pdf

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ASCCP, ASCP, ACS

From: https://www.hpv16and18.com/hcp/cervical‐cancer‐screening‐guidelines/asccp‐guidelines.html Saslow D et al, Journal of Lower Genital Tract Disease, Volume 16, Number 3, 2012

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2012 Cervical Screening Guidelines

ACS, ASCCP, ASCP: Am J Clin Pathol 2012;137:516‐542

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ACOG

  • Screening should begin at age 21 years
  • Cytology is recommended every 3 years for women aged 21‐29 years
  • Co‐testing every 5 years is preferred for women aged 30‐65 years
  • In women post hysterectomy w/o history of CIN2+, screening should be

discontinued

  • Screening guidelines don’t apply to women…

– …who have a history of cervical cancer – …have HIV infection or are immunocompromised – …who were exposed to diethylstilbestrol in utero

  • Stop screening at age 65 in women with adequate negative prior screening

and no history of CIN2+

The American College of Obstetricians and Gynecologists. ACOG Practice Bulletin. Clinical Management Guidelines for Obstetrician‐Gynecologists: Screening for Cervical Cancer. November, 2012

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N Engl J Med 2013;369:2324‐31 December 12, 2013

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BMJ 2008;377:a1754

Cytology 1x/yr Cotesting 1x/5yrs

Rationale For Screening Interval

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Rationale for Genotyping

J Natl Cancer Inst 2005; 97:1072

HPV16 HPV18 Other HR HPV HR HPV Neg.

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Rationale for Genotyping, Cont.

Am J Clin Pathol 2011;135:468‐475 cobas HPV Test – Package Insert

ASC-US & HPV18(+) NILM or ASC-US & HPV(-) NILM & HR HPV(+) ASC-US & HPV16(+) NILM & HPV16(+) ASC-US & HR HPV(+) NILM & HPV18(+)

Am J Obstet Gynecol. 2007 Oct;197(4):356.e1‐6

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Primary Screening, Age 25+

  • HR HPV‐neg. ‐> no retesting for at least 3 years
  • HPV 16/18 pos. ‐> colposcopy
  • Other HR HPV pos. ‐> cytology

Gynecol Oncol. 2015 Jan 6. pii: S0090‐8258(14)01577‐7

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Results from the ATHENA Study

Gynecol Oncol. 2015 Jan 6. pii: S0090‐8258(14)01549‐2

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Independent Results

Gynecologic Oncology 142 (2016) 120–127

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Different HPV Tests, Hard to Compare

BMC Cancer (2015) 15:968

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PLoS One. 2016 Feb 23;11(2):e0149611

HPV Testing from SurePath

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HPV Testing from SurePath

First FDA approval for SurePath (7/7/2016)

  • ASC‐US triage
  • Co‐testing with cytology for women 30+
  • Not approved for primary screening

http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm510251.htm

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Help with Complicated Algorithms

http://www.asccp.org/store‐detail2/asccp‐mobile‐app

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Cervical Cancer Screening – ARUP Consult

http://www.arupconsult.com/Topics/HPV.html

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Questions?

Estimated Cervical Cancer Mortality Worldwide in 2008

GLOBOCAN 2008, International Agency for Research on Cancer