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Innovation and a New Role for HPV Testing in Cervical Cancer

Screening

Thursday, April 18, 2013

Timothy S. Uphoff, Ph.D., D(ABMG), MLS(ASCP)CM

Section Head, Molecular Pathology, Marshfield Labs

• #14 (cancer death in women) • 12,000 cases, 4,200 deaths, (50% unscreened) • Goal: detection of preinvasive disease • Early detection: 5-year survival rate >90%

• Persistent High-Risk 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%)

Cervical Cancer

HPV Genome

digene HC2 High-Risk HPV DNA Test

13 HR HPV Types: 16/18/31/33/35/39/45/51/52/56/58/ 59/68

J Clin Invest 2006;116:1167-1173

Cervical Cancer

Wright et al NEJM 2003

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Clin Cancer Res. 2009 Nov 15;15(22):6758-62.

E6: HR-HPV types E6 protein causes degradation of p53 and activates telomerase

E7: Interaction with pRB and transactivation of E2F dependent promoters

Role of E6 and E7 in Cervical Cancer RXRα deletion and E6E7 oncogene expression are sufficient to induce cervical malignant lesions in vivo

Cancer Letters - 28 April 2012 (Vol. 317, Issue 2, Pages 226-236)

Here we introduce a mouse model that

develops spontaneously malignant cervical lesions allowing the

study of the cooperative effect between HPV16E6E7

expression and the lack of RXRα in cervical

cancer development.

J Clin Invest 2006;116:1167-1173

LSIL=Low grade squamous intraepithelial lesion CIN= Cervical intraepithelial neoplasia

What are ASCUS and LSIL?

• ASCUS and LSIL are acronyms for two mild abnormalities detected by Pap tests. – ASCUS stands for atypical squamous cells of

undetermined significance.

– LSIL for low-grade squamous intraepithelial lesion.

• A diagnosis of ASCUS means that the nature of the abnormality is uncertain or equivocal.

• A diagnosis of LSIL means that there is a more definite, but still mild, abnormality.

Population Age Screening Recommendation Comments

Less than 21 years No cervical cancer screening of

any kind

• HPV testing should not be used for

screening or ASC-US reflex in this

age group

21 - 29 years Cytology alone primary

screening every 3 years

(acceptable)

• HPV testing is recommended in cases

of ASC-US cytology

• Routine HPV “co-testing” is not

recommended in this age group

30 - 65 years HPV and cytology ‘‘co-testing’’

every 5 years (preferred)

Cytology alone every 3 years

(acceptable)

• Screening by HPV testing alone is

not recommended for most clinical

settings

Over 65 years No screening following adequate

history of negative prior screening

• Women with history of > CIN 2

should continue screening for at least

20 years

After

hysterectomy

No screening if no previous

history of > CIN 2

• Continue screening (cytology) if

there is history of > CIN 2 in the past

20 years or cervical cancer ever

HPV vaccinated Follow age-specific recommendations (same as unvaccinated women)

Summary of 2012 ACOG, ASCP, ACS and ASCCP

Cervical Cancer Screening Guidelines

M. Arbyn et al. / Vaccine 30S (2012) F88–F99

Primary Screening Women >30

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Interpretation For women aged 30 years and

older in routine clinical practice who are negative by co-testing (both HPV and

cytology), 3-year screening intervals were safe because a single negative test for HPV

was sufficient to reassure against cervical cancer over 5 years. Incorporating HPV

testing with cytology also resulted in earlier identification of women at high risk of

cervical cancer, especially adenocarcinoma. Testing for HPV without adjunctive cytology might be sufficiently sensitive for

primary screening for cervical cancer.

www.thelancet.com/oncology Vol 12 July 2011

Methods We assessed the 5-year cumulative

incidence, starting in 2003–05, of cervical cancer and CIN3 or worse for 331,818 women

aged 30 years and older who enrolled in co-testing at Kaiser Permanente Northern

California (Berkeley, CA, USA) and had adequate enrolment co-test results.

Gen-Probe marketing

14 HR HPV Types: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68

TMA

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In conclusion, our data indicate that the Aptima test is as sensitive as HC2 but more specific for detecting CIN 2 and has the potential to serve as a reliable test for both primary cervical cancer screening and the triage of borderline cytological abnormalities.

A meta analysis consisting of 8 studies. 1,839 ASC-US and 1,887 LISL cases

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False-negative results found in HPV testing Bob Ortega, The Arizona Republic January 14, 2013

Sharing Services THE DAILY REPORT Widely Used HPV Test Produces False-Negative Results, Investigation Finds

No oversight for HPV tests Bob Ortega, The Arizona Republic12:36a.m. EST January 14, 2013

01.16.13

Is Your HPV Test FDA Approved?

http://www.usatoday.com/story/news/nation/2013/01/13/hpv-testing-false-negatives/1830897/

Two LBC preservatives SurePath and ThinPrep