hpv and cervical cancer - marshfield labs
TRANSCRIPT
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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