Cervical Cancer Screening. David Quinlan December 2013

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1 Cervical Cancer Screening David Quinlan December 2013

2 Cervix

7 Cervical Cancer Screening Modest variation provincially WHO and UK begin at 25 stop at 60 Finland begin at 30 stop at 60

9 Rationale for screening update Increased knowledge about HPV Roll out of vaccination programs Technological advances in detection of precursor lesions and presence of HPV

10 Questions to be answered Which primary testing modality should be used when screening? What cohort should be targeted for screening? How frequently should screening occur? How should positive screening tests be addressed?

11 Cervical Cancer Infection with oncogenic HPV (70% = 16, 18) Develop slowly Precancerous changes usually detected through pap smear testing 80% squamous cell carcinoma Long term decreases highly correlated with organized screening programs

12 Majority of infections cleared particularly in adolescents and young women Median duration 8 months 9% persist at 24 month Persistent infections with high risk HPV more common as women get older At 30 months 9% under 30yrs 21% over 30yrs

13 Persistent infection can lead to atypia and dysplasia Most women with cervical dysplasia will experience spontaneous regression to normal tissue within 2 years

14 Clearance is higher in younger women and adolescents Additional risk factors smoking, HIV +, immunosuppression Understanding the natural history of HPV infections important in secondary prevention strategies

15 Pap Test Poor accuracy Sampling error Detection error Reduced with frequent testing False negative rate 15% Medical, economic and legal implications False positive Patient anxiety, unnecessary procedures Expensive

16 Pap test 1941 BC conventional cytology screening program Begin at 21 or 3 yrs. after sexually active Repeat every 12 month till 3 negative results then every 24 months Discontinue at 69 if 3 negative smears in last 10 years with no previous history of significant abnormalities

17 British Columbia Highly successful screening program cervical cancer Decreased incidence 78% Decreased mortality 72% Plateaued Increased incidence of adeno ca Limitations of pap test

18 Liquid Based Cytology (LBC) Advantages of LBC Higher sensitivity for Cervical Intraepithelial Neoplasia 2 (CIN2) ( ~5% greater than conventional cytology) Low rate of inadequate specimens Enhanced technologist efficiency Disadvantages More costly than conventional cytology Still relies of manual interpretation Conclusion Although an improvement it is not clear that it will produce a large increase in effectiveness

19 HPV Testing Liquid based test to detect the presence of one or more types of HPV Collected from cervix same from patient perspective Can do cytology from same sample ( LBC ) Goal is to improve sensitivity Most test for pool of HPV types High and intermediate types Genotyping now available

20 HPV Testing Hybrid capture 2 ( HC2 ) gold standard Significantly higher sensitivity: 96 % ( pap = 45% ) Lower specificity :90% ( pap = 96 % ) Better at detecting precursors associated with adenocarcinomas than pap

21 HPV testing with reflex cytology Earlier detection of high grade lesions Improved pick up of glandular lesions Risk of overtreatment Pick up lesions that would naturally regress Particularly in younger women Increased referral to colposcopy Doubled in women aged 35 60

22 Screening Cohort when to start? High risk HPV infection of a healthy adolescent does not imply the same cervical cancer risk as her older counterpart; thus screening and management protocols differ between age groups. Such messages must be understood by health providers

23 Screening Cohort UK organized screening to begin at 25 Population screening offers no benefit for women younger than 25 Acknowledge that although rare, cervical cancer does occur in young women Stress the importance of timely and effective follow up of symptoms of cancer Avoid pitfalls of overtreatment

24 Screening Cohort when to stop? Presently. Between 60 and 70 after 10 years of negative screening British Columbia 69 Continue in high risk women History of cervical cancer immunocompromised

25 A series of negative results with HPV screening will likely improve the confidence to stop screening earlier Individual history important Elevated risk for women history of dysplasia lasting up to 25 yrs. Continued participation in screening programs Increased risk of vaginal cancer

26 Risk of receiving a pap smear suggestive of cervical cancer within 3 yrs. of normal smear is 0.01% HPV negative screen extension likely to 5 6 years

27 Management of HPV positive screens Women who are 30 yrs. or older and are HPV positive but cytology negative should be rescreened in one year

28 Proposed BCCA Cervical Cancer Screening Guidelines Initiation at age 25 except in women with no sexual contact Ages screened once every 3 years using cytology Normal cytology screened at 3 year intervals High grade cytology referred to colposcopy Low grade cytology repeat in 6 months and 12 months and refer to colposcopy if persist

29 Proposed BCCA Cervical Cancer Screening Guidelines At 35 years HPV screening with reflex cytology in all women who test high risk HPV positive HPV negative women retest at 5 year interval HPV positive and low or high grade cytology refer to colposcopy

30 Proposed BCCA Cervical Cancer Screening Guidelines HPV+ and cytology negative retest in 12 months No change repeat in 24 months Negative HPV on either retest routine screening at 5 year intervals At 69 discontinue screening if at least 2 negative HPV tests in past 5 years and no biopsy confirmed CIN+ in past 25 years

31 Proposed BCCA Cervical Cancer Screening Guidelines Follow regular guidelines if : received HPV vaccine lesbian pregnant Post hysterectomy with cervix removed history of CIN2+ screen with HPV vault smear for 25 years post treatment discontinue if for benign disease and no history CIN2+

32 What to do with the following? 1. Unsatisfactory sample no endocervical glandular cells 2. Unable to interpret inflammatory exudate 3. Atypical endometrial cells 4. Clinical abnormality

34 Margins >20% of of specimens will have dysplasia extending to area of thermal artifact Cure with LEEP = (90%) ALL patients with high grade lesions require follow-up irrespective of the status of margins

35 Current Follow up Colposcopy Clinic at 6 months and 12 months 6 months colposcopy and ECC 12 months colposcopy, ECC and HPV If HPV+ve or adenoca. insitu will be followed at Colposcopy Clinic.

36 HPV testing Post LEEP Lesion in TF zone After excision of lesion women clear lesion and HPV HPV infection is mainly limited to the lesion and the TF zone

38 HPV FOCAL Study Objectives Primary: To establish the efficacy of HPV testing as standalone primary screening, followed by cytology triage (LBC) for HPV positive women Secondary: Establish the appropriate screening interval for HPV negative women Establish the appropriate clinical follow-up for women who are HPV positive Establish the cost-effectiveness of HPV testing for primary screening within the context of an organized Canadian cervical cancer screening program

39 What about Vaccination? BC program to vaccinate school girls in grades 6 &9 with Gardasil which protects against the HR HPV 16 & 18 and Genital Wart HPV 6 & 11 HPV 16 & 18 are associated with 70% of cervical cancer Clinical Trials have demonstrated that Vaccination at these ages produces strong immunity Immunity persists throughout observed follow-up (7+ years) Vaccination produces the virtual elimination of HPV 16 &18 associated CIN2+ lesions

Appropriate Use of Cytology and HPV Testing in the New Cervical Cancer Screening Guidelines

Appropriate Use of Cytology and HPV Testing in the New Cervical Cancer Screening Guidelines Tim Kremer, MD Ralph Anderson, MD 1 Objectives Describe the natural history of HPV particularly as it relates