Cervical Cancer Screening in the Era of HPV Vaccines and HPV tests. Christine M. Peterson, MD University of Virginia School of Medicine

Transcription

1 Cervical Cancer Screening in the Era of HPV Vaccines and HPV tests Christine M. Peterson, MD University of Virginia School of Medicine

2 Learning Objectives After participating in this session, attendees will be able to: Explain the biological concepts that underlie current screening guidelines. Describe the pros and cons of using HPV testing as the primary method of cervical cancer screening. Explain the differences in the recommendations for the three HPV vaccines.

3 On white 3 x 5 card, please write down 1 to 3 questions that you are hoping to have answered during this session.

4 Human Papillomavirus = The Basics HPV is a very common virus in humans. There are >100 types, about 50 of which can infect the skin of the genital tract. About 15 of those types can, but do not always, cause cancer ( oncogenic ). Infection with HPV is responsible for virtually all cervical cancer. Types 16 and 18 cause about 65% of cervical cancers. Types 31, 33, 45, 52 and 58 cause about 15% of cervical cancers Several non-oncogenic types can cause genital warts (Types 6 and 11) or other non-precancerous changes. MOST individuals infected with HPV have no disease at all!

5 The natural history of HPV infection:

6 Natural History of HPV Infection When It Leads to Cervical Cancer From: Pagliusi, Vaccine 2004

7 The goal of screening is to detect HPV-related cell changes BEFORE cancer has developed so that treatment can reduce the risk of cancer. It is not useful to detect all HPV infections because most of them will clear up without causing any cell changes.

8 Current Screening Guidelines ACOG, ACS, USPSTF, ACP (minor variations): Start at : cytology q 3 years; no screening with HPV test in women < : co-testing (cytology plus HPV test) q 5 years OR cytology q 3 years. >65 with adequate prior screening: stop, unless previous CIN2+. s/p hysterectomy: stop unless done for CIN 2+.

9 Cervical Cytology Specimen obtained by clinician Placed in preservative fluid Lab tech replaces cap with filter Applies vacuum Cells are caught on filter then Pressed onto slide OR Smeared on slide Cytotechnologist views slide under microscope and interprets cellular findings With or without computer-aided interpretation HPV DNA test can be performed on same specimen

10 PAP: Biopsy: CIN 1 CIN 2 CIN 3 From:

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12 Limitations of Cervical Cytology Interpretation is quite subjective which results in considerable intra-laboratory and inter-laboratory variation Relatively low sensitivity for the detection of high-grade cervical cancer precursors Identifies individuals with cancer precursors but not women at risk of developing cancer precursors

13 Variability of Cervical Cytology ATHENA Results Lab A Lab B Lab C Lab D Number of samples 12,294 4,218 16,979 12,442 Median age, years ASC-US 3.8% 5.2% 8.1% 9.9% Sensitivity of cytology* Sensitivity of HPV* *To detect CIN2. Wright, et al. Int J Cancer (8):

14 A Clarification Cytology = Pap HPV test = DNA test HPV effect on a Pap report is a visual impression on cytology or biopsy and is NOT the same as a positive HPV test. If a management guideline includes positive HPV that refers to the DNA test.

15 HPV testing Detects HPV DNA by PCR amplification for 14 oncogenic types. Specimens are limited to cervical cells collected in cobas PCR Cell Collection Media (Roche Molecular Systems, Inc.), PreservCyt Solution (Cytyc Corp.)

16 HPV tests HPV Triage for ASC results longstanding. HPV genotyping recent. HPV primary screening the future.

17 HPV genotyping A positive result on a HPV test does not identify which of the oncogenic types is present. Genotyping identifies types 16 or 18 when present Per ASCCP guidelines, used for women >30 with normal cytology and a positive HPV result. If 16- or 18-positive, colposcopy is recommended. Otherwise, repeat co-testing in 1 year.

18 From Castle PE et al: AJOG 2007.

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20 HPV primary screening Possible Results: Negative for all high risk HPV types. Positive for HPV 16 or HPV 18. Positive for high risk HPV, not 16 or 18. Management will be different for each result.

21 From ASCCP 2014: Wright Only for women over 24

22 ASCCP 2013 Guidelines Management by risk Immediate risk (of precancer or cancer) = cytology result. Risk over time = HPV test result. Management can be different for screening results compared with follow-up results.

23 Similar risk means similar management How can we group cytology, biopsy and HPV test results into groups of approximately equivalent risk?

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25 ASCCP Consensus Guidelines for Managing Abnormal Screening Results Massad, et al. J Low Genit Tract Dis. 2013;17:S1-S27.

26 Primary screening with HPV testing The cobas 4800 test was recently approved by the FDA for use as a primary cervical cancer screening method ONLY for women 25 and older.

27 From ASCCP 2014: Wright

28 Safety and Reassurance for the Screen Negatives =90% of population ATHENA primary screening population: women 25 years Cumulative Incidence CIN3 (%) Pap Negative A women with a negative cobas HPV Test has one-half the risk of developing CIN3 within 3 Years compared to a women with a negative Pap Wright TC, Stoler MH, Behrens C et al. Gynecol Oncol 2015;136:

29 Performance of Screening Strategies in Women Aged 25 Years No. of CIN3 Detected Strategy Total At Baseline Years 1-3 Total Missed CIN3 No. of Screening Tests No. of Colpos Colpos per CIN3 Cytology , Cotesting , HPV with genotyping and reflex cytology , Total CIN3 cases = 347 Wright, Wright TC, Stoler MH, Behrens C et al. Gynecol Oncol 2015;136:

30 Is HPV Primary Testing Better than Q 3 yr Co-testing? Gage, JNCI, 2014

31 HOWEVER, no medical organizations have changed their screening test guidelines yet BUT some institutions have changed to primary HPV screening. AND it is likely that screening guidelines will change to primary HPV testing for women over 25 within a few years.

32 Three current vaccines: HPV The Vaccine Gardasil : Types 6, 11, 16 and 18 Cervarix : Types 16 and 18 Each reduces risk of cervical cancer by ~65% NEW: Gardasil -9: Types 6, 11, 16, 18, 31, 33, 45, 52,and 58 Reduces risk of cervical cancer by ~ 80% Girls and women 9-26: any vaccine Boys and men 9-26: Gardasil or Gardasil -9

33 Screening for vaccinated women EXACTLY the same as for unvaccinated women!

34 Issues How to educate the public about HPV testing? How to usher in a culture change? Annual Paps to HPV testing every 5 years A very different approach to the content of the annual gyn visit Who keeps track of the date of the last HPV test?

35 On colorful 3 x 5 card, please write down 1 to 3 questions that you still have after this session.

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