CERVICAL CANCER SCREENING: INCORPORATING HPV TESTING   M.A. Bertrand, MD, FRCSC Professor & Head,  Division of Gynecologic...
Epidemiology – Cancer of the Cervix <ul><li>370,000 cases estimated worldwide ’93; with 200,000 deaths; </li></ul><ul><li>...
Epidemiology – Cancer of the Cervix
Epidemiology – Cancer of the Cervix <ul><li>Incidence rates (per 100,000 women) </li></ul><ul><ul><li>Finland 4.3 </li></u...
Cervical Cancer Update
Cervical Cancer Update
Epidemiology – Cancer of the Cervix Canada <ul><li>12 th  most common cancer in women in Canada </li></ul><ul><li>2005 – e...
Estimated Cervical Cancer Cases Canada, 2005 <ul><li>Number of new cases   1,350 </li></ul><ul><li>Incidence rates *    7....
Cervical Cancer in Ontario 2004 <ul><li>New cases - 510 </li></ul><ul><li>Number of Deaths - 150  </li></ul><ul><li>Death ...
Cervical Cancer – Actual / Expected Number of Deaths  (Canada)
Cervical Screening in Canada CCHOTA, May 2003, No response from PQ, NB, YK TBS 2001 N Y/N N NT/NV Mod. British N N Y BC TB...
Ontario Cervical Screening Practice Guidelines Cervical Screening Guidelines Development Committee of the Ontario Cervical...
 
 
Guidelines Revision Process Ontario Cervical Screening Program Cancer Care Ontario  Program in Evidence Based Care Cancer ...
LBC is the preferred method for cervical cytology screening; however conventional Pap smears remain an acceptable method.
A province wide cervical screening program with an adequate recall mechanism is recommended.
 
Initiation of Screening <ul><li>Data on optimal age to begin screening is limited to HPV modeling and cancer rates </li></...
Initiation of Screening ACOG, American College of Obstetricians & Gynecologists; ACS, American Cancer Society; CTFPHE, Can...
Initiation of screening <ul><li>Cervical cytology screening should be initiated within three years of first vaginal sexual...
Cessation of Screening ACOG, American College of Obstetricians & Gynecologists; ACS, American Cancer Society; CTFPHE, Cana...
Cessation of screening Screening may be discontinued after the age of 70 if there is an adequate negative screening histor...
Screening Interval ACOG, American College of Obstetricians & Gynecologists; ACS, American Cancer Society; CTFPHE, Canadian...
These recommendations do not apply to those women who have had previous abnormal Pap tests.  Screening at a 3 year interva...
Women who have sex with women should follow the same screening recommendations as women who have sex with men. Pregnant wo...
<ul><li>These are minimum guidelines only.  Certain clinical situations may require earlier follow-up/referral for colposc...
Other Timing Issues <ul><li>These recommendations do  not  apply to those women who have had previous abnormal Pap tests o...
HPV Testing ?
Human Papillomaviruses
HPV Genome : Double–stranded DNA virus
 
 
 
 
 
 
Management of cytologic abnormalities
ASCUS and LSIL Mimics
ASCUS
Risk of Harbouring HSIL <ul><li>While most ASC-US patients will have no cervical abnormality </li></ul><ul><li>9% will hav...
 
ASC-US & The ALTS Trial   <ul><li>A large USA RCT  </li></ul><ul><li>Compared management options for women ASC-US and LSIL...
Reflex HPV Testing <ul><li>Can be subsequently be performed on the residual of cells of an LBC sample if ASC-US is diagnos...
HPV Testing for  ASC-US The ALTS Trial: <ul><li>52% were HPV +ve </li></ul><ul><ul><li>10 % of HPV +ve ASCUS had HSIL </li...
The ALTS Trial: HPV Testing for  LSIL <ul><li>83% of the women with  LSIL  were HPV positive.  </li></ul><ul><li>This make...
The ALTS Trial <ul><li>Therefore, HPV DNA testing for  ASC-US:   </li></ul><ul><ul><li>was more sensitive in detecting CIN...
HPV Testing & Costs <ul><li>A 1999 assessment concluded that HPV testing in primary screening would  not  be cost-effectiv...
HPV Testing & Costs <ul><li>There will be a greater reduction in cancer  </li></ul><ul><li>at less cost than annual conven...
Ontario Guidelines ASC-US  & HPV Testing <ul><li>HPV DNA testing with cytology is therefore recommended for women aged 30 ...
 
Why 30? <ul><li>The absolute benefit of HPV DNA testing is smaller in younger women than it is in older women because:  </...
Under 30 –HPV Testing for ASC-US  Not  Recommended <ul><li>The majority of patients with ASC will be HPV+ve  </li></ul><ul...
Therefore…Under 30 <ul><li>Repeat Pap test in 6 months is recommended. </li></ul><ul><li>If that Pap test is again abnorma...
HPV Testing in 30+ with ASC-US <ul><li>If HPV  positive -  refer for colposcopy </li></ul><ul><li>If HPV negative  - repea...
In the Absence of HPV Testing  in 30+ with ASC-US <ul><li>A repeat Pap test in six months is recommended.  </li></ul><ul><...
Qualifying Statements   <ul><li>These are minimum guidelines only.  </li></ul><ul><li>Certain clinical situations may requ...
The Big Question… <ul><li>Will HPV testing help sort out Pap smear problems? </li></ul><ul><li>Yes….and….. </li></ul><ul><...
Benefits of Testing for HPV <ul><li>Will reduce referrals to colpo clinic for ASC-US HPV –ve patients.  </li></ul><ul><ul>...
Problems with HPV Screening <ul><li>ASC-US HPV + pts referred to Colpo: </li></ul><ul><ul><li>Many will a normal cervix on...
Problems with HPV Screening <ul><li>We must resist the urge, or, being urged to, treat the cervix in the absence of biopsy...
Problems with HPV Screening <ul><li>Women with mildly abnormal smear results &  are HPV +ve experience:  </li></ul><ul><ul...
Problems with HPV Screening <ul><li>Women struggle to balance:  </li></ul><ul><ul><li>the anxiety of knowing that HPV infe...
Negative Outcomes with HPV Testing <ul><li>HPV testing in screening may shift the overall societal perspective of cervical...
HPV Education <ul><li>For adolescents and young adults, media sources, parents and friends play a more important role in H...
New Health Technology - Beneficial <ul><li>Improved disease outcome; </li></ul><ul><li>Reduction in use of invasive proced...
Improved disease outcome <ul><li>The object of  cervical cancer screening  is to prevent the development and death from ca...
Improved disease outcome <ul><li>Studies have shown that it is possible to find more high grade lesions when HPV testing i...
Improved disease outcome <ul><li>In BC,  most cancers of the cervix arise  not from technical deficiencies of Pap Smears, ...
Low-Grade Squamous Intraepithelial Lesion - LSIL
Low Grade SIL
Management of LSIL <ul><li>ALTS - LSIL – 83% HPV positive </li></ul><ul><li>Therefore HPV triage was abandoned </li></ul><...
Management of LSIL <ul><li>Age is a factor since many young women with LSIL have transient lesions </li></ul><ul><li>Spitz...
High-Grade squamous Intraepithelial Lesion - HSIL
Women with AGC should also receive endocervical and endometrial sampling, where appropriate.  High grade SIL, ASC-H, Atypi...
Potential Use of HPV Testing <ul><li>Primary screening tool  for women over 30; </li></ul><ul><li>Triage tool  for women o...
Next… <ul><li>HPV Vaccines ! </li></ul>
HPV Vaccines
HPV Vaccines <ul><li>Who? </li></ul><ul><li>When? </li></ul><ul><li>Cross-protection? </li></ul><ul><li>Alterations in Cer...
Conclusion <ul><li>Cancer of the cervix is a relatively less common cancer; </li></ul><ul><li>The goal of screening is the...
Conclusion <ul><li>Overall, the great majority of women referred for colposcopy still do not develop CIN 2-3 and very few ...
Conclusion <ul><li>The role of HPV testing within a cervical screening program has yet to be fully understood; </li></ul><...
Conclusion <ul><li>Other issues that have yet to be addressed: </li></ul><ul><ul><li>Patient preference </li></ul></ul><ul...
Thank you for your attention
Question?
 
Sensitivity for CIN 3
Negative Predictive Value
Cervical Cancer Screening Programs and Practices, Canada 2001
<ul><li>What is the optimal cervical screening tool? </li></ul><ul><li>Do organized cervical screening programs reduce the...
ALTS Trial -ASCUS Triage As compared to prevalence of CIN 3 in immediate  colposcopy arm – 11.4% 96% 99% NPV for CIN 3 17%...
 
Next Steps <ul><li>Draft revision </li></ul><ul><li>Stakeholder Review </li></ul><ul><li>Final revision </li></ul><ul><li>...
ALTS – Results by age % Referred to Colp Sensitivity for CIN 3 50% 64% Cytology  follow up 31% 65% HPV  testing 91% 88% Cy...
CYTOLOGY COLPO .>MOD REPEAT @ 6 MONTHS PERSISTENT OF MILD  FOR 2 YRS OR > MOD Recall @ 24 months  Neg Mild PRIMARY SCREENI...
PRIMARY SCREENING FOR WOMEN OVER 30 HPV:  Screen every 3 years HPV Cytology Colpo + > Or = mild Recall @ 36 m  Neg Repeat ...
TRIAGE of MILD DYSPLASIA for WOMEN OVER 30 Current Practice: Women > 30 years, last smear mild Repeat cytology @ 6 months ...
TRIAGE of MILD DYSPLASIA for WOMEN OVER 30 HPV Testing: Use at 6 months Mild repeat @ 6 months HPV Cytology Colpo Repeat @...
TRIAGE of High Risk WOMEN OVER 30 Current Practice: High risk flag set, last smear Neg (72,000 women) High Risk  Cytology ...
TRIAGE of High Risk WOMEN OVER 30 HPV Testing: Use at 6 months High Risk HPV Cytology Colpo Recall @ 12 months HPV & Cytol...
Ontario HPV Pilot Project Cancer Care Ontario and Ministry of Health <ul><li>To Study the Feasibility of Implementing Huma...
 
 
PRIMARY SCREENING FOR WOMEN OVER 30 <ul><li>HPV: Screen every 3 years </li></ul><ul><li>Probable effect of change to curre...
TRIAGE of MILD DYSPLASIA for WOMEN OVER 30 <ul><li>HPV: Use at 6 months </li></ul><ul><li>Probable effect of change to cur...
TRIAGE of High Risk WOMEN OVER 30 <ul><li>HPV: Use at 6 months </li></ul><ul><li>Probable effect of change to current prac...
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    1. 1. CERVICAL CANCER SCREENING: INCORPORATING HPV TESTING M.A. Bertrand, MD, FRCSC Professor & Head, Division of Gynecologic Oncology, University of Western Ontario, London, Ontario, Canada
    2. 2. Epidemiology – Cancer of the Cervix <ul><li>370,000 cases estimated worldwide ’93; with 200,000 deaths; </li></ul><ul><li>3 rd most common cancer in women worldwide; </li></ul><ul><li>80% of all cases of cervical cancer occur in the developing countries; </li></ul><ul><li>Estimates of the prevalence of pre-invasive lesions range from 1.25 – 3 .0 million (USA) </li></ul>
    3. 3. Epidemiology – Cancer of the Cervix
    4. 4. Epidemiology – Cancer of the Cervix <ul><li>Incidence rates (per 100,000 women) </li></ul><ul><ul><li>Finland 4.3 </li></ul></ul><ul><ul><li>Canada 7.6 (‘05 estimated rates) </li></ul></ul><ul><ul><li>France 9.8 </li></ul></ul><ul><ul><li>Romania 23.9 </li></ul></ul><ul><ul><li>Serbia 27.4 </li></ul></ul><ul><ul><li>Ethiopia 35.5 </li></ul></ul><ul><ul><li>Latin America 37 </li></ul></ul>
    5. 5. Cervical Cancer Update
    6. 6. Cervical Cancer Update
    7. 7. Epidemiology – Cancer of the Cervix Canada <ul><li>12 th most common cancer in women in Canada </li></ul><ul><li>2005 – estimated 1,350 new cases </li></ul><ul><li>approximately 400 deaths </li></ul><ul><li>The rate of decline in incidence has slowed in the last 20 years; </li></ul><ul><li>Trend of increasing incidence in white women < 50 yrs of age (USA & Europe) </li></ul>
    8. 8. Estimated Cervical Cancer Cases Canada, 2005 <ul><li>Number of new cases 1,350 </li></ul><ul><li>Incidence rates * 7.6 ( ’77 – 15.4) </li></ul><ul><li>Number of deaths 400 </li></ul><ul><li>Mortality rates * 2.0 (’77 – 4.8) </li></ul><ul><li> * rate per 100,000 </li></ul>National Cancer Institute of Canada: Canadian Cancer Statistics 2005
    9. 9. Cervical Cancer in Ontario 2004 <ul><li>New cases - 510 </li></ul><ul><li>Number of Deaths - 150 </li></ul><ul><li>Death to Case Ratio = 30/100 </li></ul><ul><li>A reduction in incidence rates </li></ul><ul><li>From 21.6 /100,000 in 1969 </li></ul><ul><li>to 7 in 2004 </li></ul><ul><ul><li>Canadian Cancer Statistics, National Cancer Institute of Canada, 2004 </li></ul></ul>
    10. 10. Cervical Cancer – Actual / Expected Number of Deaths (Canada)
    11. 11. Cervical Screening in Canada CCHOTA, May 2003, No response from PQ, NB, YK TBS 2001 N Y/N N NT/NV Mod. British N N Y BC TBS 2001 N N Y Alberta TBS 2001 N N Y Saskatchewan TBS 2001 N N Y Manitoba TBS 1991 N N Y PEI TBS 2001 N N Y Nova Scotia TBS 2001 On demand N Y Newfoundland TBS 2001 On demand Y Y Ontario Terminology HPV Testing Liquid Based Cytology Screening Program Province/ Territory
    12. 12. Ontario Cervical Screening Practice Guidelines Cervical Screening Guidelines Development Committee of the Ontario Cervical Screening Program and the Gynecology Cancer Disease Site Group of Cancercare Ontario
    13. 15. Guidelines Revision Process Ontario Cervical Screening Program Cancer Care Ontario Program in Evidence Based Care Cancer Care Ontario GYN Disease Site Group Screening Guidelines Development Committee QMPLS “ Weigh the Evidence”
    14. 16. LBC is the preferred method for cervical cytology screening; however conventional Pap smears remain an acceptable method.
    15. 17. A province wide cervical screening program with an adequate recall mechanism is recommended.
    16. 19. Initiation of Screening <ul><li>Data on optimal age to begin screening is limited to HPV modeling and cancer rates </li></ul><ul><li>Minimal risk of significant lesion within 3-5 yrs of first HPV contact </li></ul><ul><li>Incidence of cervical cancer is low < 20 yrs </li></ul><ul><li>Potential harm to screening adolescent women </li></ul><ul><ul><li>false positives, transient lesions, anxiety </li></ul></ul>
    17. 20. Initiation of Screening ACOG, American College of Obstetricians & Gynecologists; ACS, American Cancer Society; CTFPHE, Canadian Task Force on the Periodic Health Examination; IARC, International Agency for Research on Cancer; NHS, National Health Service, NZGG, New Zealand Guidelines Group; USPSTF, United States Preventive Services Task Force. All sexually active women CTFPHE 20 years of age for sexually active women NZGG 21 year of age or within 3 years of first intercourse ACOG, ACS, USPSTF 25 years of age IARC, NHS
    18. 21. Initiation of screening <ul><li>Cervical cytology screening should be initiated within three years of first vaginal sexual activity. </li></ul><ul><li>All women who are or have ever been sexually active should be screened. </li></ul>
    19. 22. Cessation of Screening ACOG, American College of Obstetricians & Gynecologists; ACS, American Cancer Society; CTFPHE, Canadian Task Force on the Periodic Health Examination; IARC, International Agency for Research on Cancer; NHS, National Health Service, NZGG, New Zealand Guidelines Group; USPSTF, United States Preventive Services Task Force. Not enough evidence ACOG Age 65 USPSTF Age 70 NZGG Age 65 NHS Age 70 ACS Age 65 IARC
    20. 23. Cessation of screening Screening may be discontinued after the age of 70 if there is an adequate negative screening history in the previous 10 years (i.e. 3-4 negative tests).
    21. 24. Screening Interval ACOG, American College of Obstetricians & Gynecologists; ACS, American Cancer Society; CTFPHE, Canadian Task Force on the Periodic Health Examination; IARC, International Agency for Research on Cancer; NHS, National Health Service, NZGG, New Zealand Guidelines Group; USPSTF, United States Preventive Services Task Force. At least every 3 yrs USPSTF Every 3 yrs CTFPHE Every 3 yrs NZGG Every 3 yrs, age 25-50 then every 5 yrs NHS Annually under age 30 Every 2-3 yrs over age 30 ACOG, ACS Every 3 yrs, age 25-49 IARC
    22. 25. These recommendations do not apply to those women who have had previous abnormal Pap tests. Screening at a 3 year interval is recommended, supported by an adequate recall mechanism. Screening interval ·  Screening should be done annually until there are 3 consecutive negative Pap tests. ·  Screening should continue every 2 to 3 years after three annual negative Pap tests.
    23. 26. Women who have sex with women should follow the same screening recommendations as women who have sex with men. Pregnant women should be screened the same as women who are not pregnant . Discontinue cervical screening in women who have undergone total hysterectomy for benign causes. Immunocompromised or HIV positive women should receive annual screening.
    24. 27. <ul><li>These are minimum guidelines only. Certain clinical situations may require earlier follow-up/referral for colposcopy. </li></ul><ul><li>Any repeat Pap test should not be performed earlier than three months. </li></ul><ul><li>The Pap test should not be used in the assessment of a visible cervical lesion. These patients require biopsy for accurate diagnosis. </li></ul>
    25. 28. Other Timing Issues <ul><li>These recommendations do not apply to those women who have had previous abnormal Pap tests or treatment for SIL </li></ul><ul><ul><li>they should have at least yearly screening. </li></ul></ul><ul><li>Screening at a three-year interval is recommended if there is an adequate recall mechanism in place. </li></ul><ul><li>Women who have not been screened in more than five years should be screened annually until there are three consecutive negative Pap tests. </li></ul>
    26. 29. HPV Testing ?
    27. 30. Human Papillomaviruses
    28. 31. HPV Genome : Double–stranded DNA virus
    29. 38. Management of cytologic abnormalities
    30. 39. ASCUS and LSIL Mimics
    31. 40. ASCUS
    32. 41. Risk of Harbouring HSIL <ul><li>While most ASC-US patients will have no cervical abnormality </li></ul><ul><li>9% will have HSIL. </li></ul><ul><li>With LSIL. </li></ul><ul><ul><li>up to 18.3% will have HSIL. </li></ul></ul>
    33. 43. ASC-US & The ALTS Trial <ul><li>A large USA RCT </li></ul><ul><li>Compared management options for women ASC-US and LSIL </li></ul><ul><li>Randomization was to one of three management arms: </li></ul><ul><ul><li>repeat conventional cytology </li></ul></ul><ul><ul><li>reflex HPV DNA testing, or </li></ul></ul><ul><ul><li>immediate colposcopy. </li></ul></ul>
    34. 44. Reflex HPV Testing <ul><li>Can be subsequently be performed on the residual of cells of an LBC sample if ASC-US is diagnosed. </li></ul><ul><li>It is cost effective because a second sample (and clinic visit) is not necessary. </li></ul>
    35. 45. HPV Testing for ASC-US The ALTS Trial: <ul><li>52% were HPV +ve </li></ul><ul><ul><li>10 % of HPV +ve ASCUS had HSIL </li></ul></ul><ul><li>48% were HPV –ve and spared colposcopy. </li></ul><ul><li>only 31% of women >28 years old had +ve HPV test and 69 % spared colposcopy. </li></ul><ul><li>a -ve HPV result = a 99.5% chance of not missing a significant lesion. </li></ul>
    36. 46. The ALTS Trial: HPV Testing for LSIL <ul><li>83% of the women with LSIL were HPV positive. </li></ul><ul><li>This makes HPV testing for LSIL unnecessary </li></ul><ul><li>Most of these women will be referred to colposcopy any way. </li></ul>
    37. 47. The ALTS Trial <ul><li>Therefore, HPV DNA testing for ASC-US: </li></ul><ul><ul><li>was more sensitive in detecting CIN 3 than conventional cytology </li></ul></ul><ul><ul><li>resulted in fewer referrals for colposcopy among women over 29 years </li></ul></ul><ul><ul><li>conventional cytology alone provides adequate triage in women with LSIL. </li></ul></ul><ul><ul><li>Sherman ME, et al; Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesion Triage Study Group. Effects of age and human papilloma viral load on colposcopy triage: J Natl Cancer Inst. 2002;94:102-7. </li></ul></ul>
    38. 48. HPV Testing & Costs <ul><li>A 1999 assessment concluded that HPV testing in primary screening would not be cost-effective unless: </li></ul><ul><ul><li>screening intervals be substantially lengthened for HPV –ve patients, </li></ul></ul><ul><ul><li>the age at which women are no longer need screening be lowered (e.g. 60) following a series of negative HPV tests. </li></ul></ul><ul><ul><ul><ul><li>Cuzick J, Beverley E, Ho L, Terry G, Sapper H, Mielzynska I et al. HPV testing in primary screening of older women. Br J Cancer 1999; 81(3):554-558. </li></ul></ul></ul></ul>
    39. 49. HPV Testing & Costs <ul><li>There will be a greater reduction in cancer </li></ul><ul><li>at less cost than annual conventional cytology </li></ul><ul><li>for women aged 30 years and more if: </li></ul><ul><ul><li>Screening occurs every 2- or 3-years </li></ul></ul><ul><ul><li>reflex HPV testing is used for equivocal results </li></ul></ul><ul><ul><ul><li>Goldie SJ, Kim JJ, Wright TC. Cost-effectiveness of human papillomavirus DNA testing for cervical cancer screening in women aged 30 years or more. Obstet Gynecol 2004; 103(4):619-631. </li></ul></ul></ul>
    40. 50. Ontario Guidelines ASC-US & HPV Testing <ul><li>HPV DNA testing with cytology is therefore recommended for women aged 30 and older with ASCUS. </li></ul><ul><ul><li>Lower false +ve rate </li></ul></ul><ul><ul><ul><li>i.e. +HPV and –ve colpo </li></ul></ul></ul><ul><li>In women under the age of 30, </li></ul><ul><ul><li>HPV testing is not recommended </li></ul></ul>
    41. 52. Why 30? <ul><li>The absolute benefit of HPV DNA testing is smaller in younger women than it is in older women because: </li></ul><ul><ul><li>the high rate of transient HPV infections and </li></ul></ul><ul><ul><li>the very low incidence of cervical cancer. </li></ul></ul><ul><li>The benefits of HPV DNA testing among women with ASCUS increase along a continuum with age, </li></ul><ul><li>The likelihood of harms from HPV DNA testing (unnecessary anxiety, treatment and cost) diminish as age increases. </li></ul><ul><li>The balance of benefits and potential harms, therefore, grows more favorable as women age. </li></ul>
    42. 53. Under 30 –HPV Testing for ASC-US Not Recommended <ul><li>The majority of patients with ASC will be HPV+ve </li></ul><ul><li>Most of these are transient infections </li></ul><ul><ul><li>Lasting no more than 4 to 8 months </li></ul></ul><ul><li>Therefore HPV testing is not helpful in triage </li></ul><ul><li>The risk of missing a cancer is extremely low </li></ul>
    43. 54. Therefore…Under 30 <ul><li>Repeat Pap test in 6 months is recommended. </li></ul><ul><li>If that Pap test is again abnormal, </li></ul><ul><ul><li>refer for colposcopy. </li></ul></ul><ul><li>If that Pap test is normal, </li></ul><ul><ul><li>repeat cytology in another 6 months. </li></ul></ul><ul><li>Once a woman has had 2 negative Pap tests results, she should return to routine screening. </li></ul>
    44. 55. HPV Testing in 30+ with ASC-US <ul><li>If HPV positive - refer for colposcopy </li></ul><ul><li>If HPV negative - repeat LBC in 12 months </li></ul><ul><li>Once a woman has had two negative LBC Pap tests, </li></ul><ul><ul><li>she should then return to routine screening. </li></ul></ul>
    45. 56. In the Absence of HPV Testing in 30+ with ASC-US <ul><li>A repeat Pap test in six months is recommended. </li></ul><ul><li>If the Pap test is again abnormal, </li></ul><ul><ul><li>refer for colposcopy. </li></ul></ul><ul><li>If the Pap test is normal, </li></ul><ul><ul><li>repeat the Pap in another six months. </li></ul></ul><ul><li>Once there has been 2 negative Pap tests at 6 mo intervals, then return to routine screening. </li></ul>
    46. 57. Qualifying Statements <ul><li>These are minimum guidelines only. </li></ul><ul><li>Certain clinical situations may require earlier follow-up/referral for colposcopy. </li></ul><ul><li>A repeat Pap test should not be performed earlier than 3 months following the original. </li></ul><ul><li>A Pap test should not be used as the sole assessment of a visible cervical lesion. </li></ul><ul><ul><li>These patients require a biopsy for accurate diagnosis. </li></ul></ul>
    47. 58. The Big Question… <ul><li>Will HPV testing help sort out Pap smear problems? </li></ul><ul><li>Yes….and….. </li></ul><ul><li>No </li></ul><ul><li>In fact, it adds new problems… </li></ul>
    48. 59. Benefits of Testing for HPV <ul><li>Will reduce referrals to colpo clinic for ASC-US HPV –ve patients. </li></ul><ul><ul><li>reduces the false +ve rate of cytology alone </li></ul></ul><ul><li>HPV +ve patients can be followed at defined intervals so that any SIL (10% risk of HSIL) is detected early and treated. </li></ul><ul><li>Woman with negative results on both HPV and cytology testing have very low risk of developing a high-grade lesion over an extended interval. </li></ul><ul><ul><ul><li>Sherman ME, Lorincz AT, Scott DR, Wacholder S, Castle PE, Glass AG et al. Baseline cytology, human papillomavirus testing, and risk for cervical neoplasia: a 10-year cohort analysis. J Natl Cancer Inst 2003; 95(1):46-52. </li></ul></ul></ul>
    49. 60. Problems with HPV Screening <ul><li>ASC-US HPV + pts referred to Colpo: </li></ul><ul><ul><li>Many will a normal cervix on colposcopic examination </li></ul></ul><ul><li>Patients will struggle with being told their cervix is colposcopically normal but they have an oncogenic virus infection </li></ul><ul><li>only about 10% will develop HSIL </li></ul>
    50. 61. Problems with HPV Screening <ul><li>We must resist the urge, or, being urged to, treat the cervix in the absence of biopsy proven LSIL or HSIL. </li></ul><ul><li>A recent randomized trial from the U.K. (HART) and the ASCCP Guidelines recommend </li></ul><ul><ul><li>repeat Pap & HPV testing at 12 month intervals indefinitely </li></ul></ul><ul><ul><ul><ul><li>Cuzick J, et al. Management of women who test positive for high-risk types of human papillomavirus: the HART study. Lancet 2003; 362(9399):1871-1876. </li></ul></ul></ul></ul>
    51. 62. Problems with HPV Screening <ul><li>Women with mildly abnormal smear results & are HPV +ve experience: </li></ul><ul><ul><li>high levels of anxiety </li></ul></ul><ul><ul><li>exacerbated by an inability to understand the meaning of the results </li></ul></ul><ul><ul><li>resulting in an fear of cancer far above the risk associated with ASCUS/LSIL </li></ul></ul><ul><li>Those who were HPV –ve were no less anxious than HPV +ve women. </li></ul><ul><li>There is a dearth of research on the merits and consequences of conveying this information. </li></ul><ul><ul><ul><li>Esther Maissi et al. Psychological impact of HPV testing in women with borderline or mildly dyskaryotic cervical smear test results.  British Medical Journal 2004; 328: 1293-6 </li></ul></ul></ul>
    52. 63. Problems with HPV Screening <ul><li>Women struggle to balance: </li></ul><ul><ul><li>the anxiety of knowing that HPV infection causes cervical cancer </li></ul></ul><ul><li>with </li></ul><ul><ul><li>the fact that HPV infection often regresses without treatment. </li></ul></ul><ul><li>They are also confused that cytology results are normal in the presence of HPV infection. </li></ul><ul><ul><ul><ul><li>Anhang R, Wright TC, Jr., Smock L, Goldie SJ. Women's desired information about human papillomavirus. Cancer 2004; 100(2):315-320. </li></ul></ul></ul></ul>
    53. 64. Negative Outcomes with HPV Testing <ul><li>HPV testing in screening may shift the overall societal perspective of cervical cancer. </li></ul><ul><li>The link between STD and cervical cancer was always present but now it will be explicit. </li></ul><ul><li>This may lead to decreases in screening due to stigma of screening participants. </li></ul><ul><li>Compliance with follow up visits also remains a concern. </li></ul>
    54. 65. HPV Education <ul><li>For adolescents and young adults, media sources, parents and friends play a more important role in HPV education than health professionals </li></ul><ul><li>Adolescents have indicated that, compared with other STIs, they know and were taught the least about HPV </li></ul><ul><li>If not carefully delivered, negative outcomes including </li></ul><ul><ul><li>stigma, </li></ul></ul><ul><ul><li>decreased screening, </li></ul></ul><ul><ul><li>and anxiety following a positive test, </li></ul></ul>
    55. 66. New Health Technology - Beneficial <ul><li>Improved disease outcome; </li></ul><ul><li>Reduction in use of invasive procedures or side-effects; </li></ul><ul><li>Reduction in costs </li></ul>
    56. 67. Improved disease outcome <ul><li>The object of cervical cancer screening is to prevent the development and death from cancer of the cervix; </li></ul><ul><li>No studies to show reduction in invasive cancer of the cervix through the use of HPV testing in screening or triage; </li></ul>
    57. 68. Improved disease outcome <ul><li>Studies have shown that it is possible to find more high grade lesions when HPV testing is added to cytology; </li></ul><ul><li>Whether this leads to meaningful improvement in disease control is unclear </li></ul>
    58. 69. Improved disease outcome <ul><li>In BC, most cancers of the cervix arise not from technical deficiencies of Pap Smears, but from insufficient screening from the general population , it is unlikely that adding HPV screening would improve in outcomes. </li></ul>
    59. 70. Low-Grade Squamous Intraepithelial Lesion - LSIL
    60. 71. Low Grade SIL
    61. 72. Management of LSIL <ul><li>ALTS - LSIL – 83% HPV positive </li></ul><ul><li>Therefore HPV triage was abandoned </li></ul><ul><li>The CIN 3 follow up rate of LSIL was similar to ASCUS/ HPV + </li></ul><ul><li>BUT – There were concerns that in Ontario recommending colposcopy for all women with LSIL would overwhelm the colposcopy system </li></ul>
    62. 73. Management of LSIL <ul><li>Age is a factor since many young women with LSIL have transient lesions </li></ul><ul><li>Spitzer, ASCCP - “ Even though adolescents have a high incidence of LSIL, they have a very low incidence of developing rapid onset cervical cancer. For selected adolescents, acceptable options for follow-up consist of repeat cervical cytologic analysis at 6 and 12 months” </li></ul><ul><li>BUT no evidence to support a specific age </li></ul>
    63. 74. High-Grade squamous Intraepithelial Lesion - HSIL
    64. 75. Women with AGC should also receive endocervical and endometrial sampling, where appropriate. High grade SIL, ASC-H, Atypical Glandular cells Colposcopy
    65. 76. Potential Use of HPV Testing <ul><li>Primary screening tool for women over 30; </li></ul><ul><li>Triage tool for women over 30 with a mild atypia that are recommended for 6 month repeat smear; </li></ul><ul><li>As a risk assessment tool for women over 30 with high risk flag whose last smear was negative. </li></ul>
    66. 77. Next… <ul><li>HPV Vaccines ! </li></ul>
    67. 78. HPV Vaccines
    68. 79. HPV Vaccines <ul><li>Who? </li></ul><ul><li>When? </li></ul><ul><li>Cross-protection? </li></ul><ul><li>Alterations in Cervical Cancer Screening? </li></ul>
    69. 80. Conclusion <ul><li>Cancer of the cervix is a relatively less common cancer; </li></ul><ul><li>The goal of screening is the prevention of cancer of the cervix; </li></ul>
    70. 81. Conclusion <ul><li>Overall, the great majority of women referred for colposcopy still do not develop CIN 2-3 and very few will develop cancer; </li></ul><ul><li>Critical to optimize postcolposcopy management to detect initially missed CIN 2-3 while avoiding overtreatment of the many women referred . </li></ul>
    71. 82. Conclusion <ul><li>The role of HPV testing within a cervical screening program has yet to be fully understood; </li></ul><ul><li>HPV vaccines have the potential to eliminate Cancer of the Cervix… </li></ul><ul><li>Prudence must be used when introducing the HPV vaccine within the context of an existing Cervical Cancer Screening Program </li></ul>
    72. 83. Conclusion <ul><li>Other issues that have yet to be addressed: </li></ul><ul><ul><li>Patient preference </li></ul></ul><ul><ul><li>Convenience </li></ul></ul><ul><ul><li>Quality of life </li></ul></ul><ul><ul><li>Cost – effectiveness </li></ul></ul>
    73. 84. Thank you for your attention
    74. 85. Question?
    75. 87. Sensitivity for CIN 3
    76. 88. Negative Predictive Value
    77. 89. Cervical Cancer Screening Programs and Practices, Canada 2001
    78. 90. <ul><li>What is the optimal cervical screening tool? </li></ul><ul><li>Do organized cervical screening programs reduce the incidence / mortality of cervical cancer compared to spontaneous cervical screening? </li></ul><ul><li>What is the most appropriate time for initiation and cessation of cervical screening? </li></ul><ul><li>At what time interval should women be screened? </li></ul><ul><li>How should women in special circumstances be screened? </li></ul><ul><li>What is the optimal management for women with abnormal cytology (up to but not including colposcopy/management)? </li></ul>Project Objectives
    79. 91. ALTS Trial -ASCUS Triage As compared to prevalence of CIN 3 in immediate colposcopy arm – 11.4% 96% 99% NPV for CIN 3 17% 20% PPV for CIN 3 58% 53% Referred to colp 83.4% 92.4% Sensitivity – CIN 3 ASCUS / ASCUS ASCUS / HPV +
    80. 93. Next Steps <ul><li>Draft revision </li></ul><ul><li>Stakeholder Review </li></ul><ul><li>Final revision </li></ul><ul><li>Approval – OCSCG, PEBC, GYN DSG </li></ul><ul><li>Publication / Education </li></ul><ul><li>Next steps </li></ul><ul><ul><li>Implementation </li></ul></ul><ul><ul><li>Management guidelines </li></ul></ul>
    81. 94. ALTS – Results by age % Referred to Colp Sensitivity for CIN 3 50% 64% Cytology follow up 31% 65% HPV testing 91% 88% Cytology follow up 94% 96% HPV testing Age >= 29 years Age 23-28 years
    82. 95. CYTOLOGY COLPO .>MOD REPEAT @ 6 MONTHS PERSISTENT OF MILD FOR 2 YRS OR > MOD Recall @ 24 months Neg Mild PRIMARY SCREENING FOR WOMEN OVER 30 Current Practice : Women over 30, 3 consecutive negatives, not high risk, recall @ 24 m .
    83. 96. PRIMARY SCREENING FOR WOMEN OVER 30 HPV: Screen every 3 years HPV Cytology Colpo + > Or = mild Recall @ 36 m Neg Repeat @ 12 m. HPV & cytology Neg
    84. 97. TRIAGE of MILD DYSPLASIA for WOMEN OVER 30 Current Practice: Women > 30 years, last smear mild Repeat cytology @ 6 months COLPO > Mod or 3rd consec. mild Recall @ 6 months Mild Recall @ 12 months Neg
    85. 98. TRIAGE of MILD DYSPLASIA for WOMEN OVER 30 HPV Testing: Use at 6 months Mild repeat @ 6 months HPV Cytology Colpo Repeat @ 12 m. HPV & Cytology Neg > Mild Pos Recall @ 24 months Neg
    86. 99. TRIAGE of High Risk WOMEN OVER 30 Current Practice: High risk flag set, last smear Neg (72,000 women) High Risk Cytology Repeat Cytology @ 6 months Mild Colpo > Mod Recall @ 12 months Neg
    87. 100. TRIAGE of High Risk WOMEN OVER 30 HPV Testing: Use at 6 months High Risk HPV Cytology Colpo Recall @ 12 months HPV & Cytology Neg > Mild + Turn High Risk & recall @ 24 months Neg
    88. 101. Ontario HPV Pilot Project Cancer Care Ontario and Ministry of Health <ul><li>To Study the Feasibility of Implementing Human Papillomavirus Testing in the Family Practice Setting in Ontario </li></ul><ul><li>Funded by the Ontario Women's Health Council </li></ul><ul><li>Looking at screening effectiveness </li></ul><ul><li>Cost effectiveness </li></ul><ul><li>Feasibility for hard to reach women </li></ul><ul><li>HPV testing for ASC-US Paps </li></ul><ul><ul><li>+ve HPV  Colposcopy </li></ul></ul><ul><ul><li>-ve HPV  back to routine Pap tests </li></ul></ul>
    89. 104. PRIMARY SCREENING FOR WOMEN OVER 30 <ul><li>HPV: Screen every 3 years </li></ul><ul><li>Probable effect of change to current practice </li></ul><ul><ul><li>Reduction in cytology </li></ul></ul><ul><ul><li>Stable in colposcopy referrals </li></ul></ul><ul><ul><li>Increase in HPV testing </li></ul></ul>
    90. 105. TRIAGE of MILD DYSPLASIA for WOMEN OVER 30 <ul><li>HPV: Use at 6 months </li></ul><ul><li>Probable effect of change to current practice </li></ul><ul><ul><li>Reduction in cytology </li></ul></ul><ul><ul><li>Stable in colposcopy referrals </li></ul></ul><ul><ul><li>Increase in HPV testing </li></ul></ul>
    91. 106. TRIAGE of High Risk WOMEN OVER 30 <ul><li>HPV: Use at 6 months </li></ul><ul><li>Probable effect of change to current practice </li></ul><ul><ul><li>Reduction in cytology </li></ul></ul><ul><ul><li>Stable in colposcopy referrals </li></ul></ul><ul><ul><li>Increase in HPV testing </li></ul></ul>

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