1. Spotlight on Cervical Cancer Screening
Slide Objective: Title slide

2. Cervical Cancer Screening

3. Ontario Cancer Statistics 2013
Cancer Type
# New Cases
# Deaths
Cervical
610 (F)
150 (F) 3
Slide Objective: Present burden of disease for breast, cervical and colorectal cancer
Context for Cervical Cancer:
The end point for cervical cancer screening is cervical intraepithelial neoplasia (CIN) 2 and/or CIN 3, NOT cervical cancer.
The aim of screening is to prevent cervical cancer.
The benefit of widespread cervical cancer screening in Ontario is a reduced incidence of cervical cancer cases.
Less-developed countries that do not have widespread cervical cancer screening with the Pap test have much higher cervical cancer incidence and mortality rates compared to Ontario and Canada.
Background:
Breast cancer (GLOBOCAN 2008)
Global incidence rate of 38.9 per 100,000 compared to 83.2 per 100,000 in Canada
Global mortality rate of 12.4 per 100,000 compared to 15.6 per 100,000 in Canada
Cervical cancer (GLOBOCAN 2008)
Incidence rate globally is more than two times higher than in Canada (global cervical cancer incidence rate is 15.2 per 100,000 compared to 6.6 per 100,000 in Canada)
Mortality rate globally is four times higher than in Canada (global cervical cancer mortality rate of 7.8 per 100,000 compared to 1.9 per 100,000 in Canada)
Colorectal cancer (GLOBOCAN 2008)
Global incidence of 17.2 per 100,000 compared to 38.1 per 100,000 in Canada
Global mortality rate of 8.2 per 100,000 compared to 11.7 per 100,000 in Canada
References:
Canadian Cancer Society’s Advisory Committee on Cancer Statistics. Canadian Cancer Statistics Toronto: Canadian Cancer Society; Available online:
Ferlay J, Shin HR, Bray F, Forman D, Mathers C and Parkin DM. GLOBOCAN 2008 v2.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 10 [Internet]. Lyon, France: International Agency for Research on Cancer; Available from: accessed September 19, 2013

4. Burden of Disease in Ontario
4/17/2017
Burden of Disease in Ontario
Estimated 610 women will be diagnosed and will die of cervical cancer in 2013
Up to 80,000 abnormal Pap tests require assessment each year
4th most common cancer among women under age 50
Slide Objective: Provide a brief overview of the burden of disease for cervical cancer
Background Information:
Cervical cancer is almost entirely preventable with regular screening, appropriate and timely follow-up of abnormal Pap test results and, recently, HPV immunization. Compared to most other cancers, cervical cancer is diagnosed about 10 years earlier.
References:
Ontario Agency for Health Protection and Promotion and the Institute for Clinical Evaluative Sciences. Ontario Burden of Infectious Disease (OBOID) Study. December 2010.
Canadian Cancer Society’s Advisory Committee on Cancer Statistics, Canadian Cancer Statistics Toronto, ON: Canadian Cancer Society, 2013.
Cancer Care Ontario. Ontario Cancer Fact: Long-term decline in cervical cancer incidence continues. December Available at Accessed July 16, 2013.

5. Sensitivity and Specificity
Cancer Site
Test
Sensitivity
Specificity
Cervical
Pap test
44% to 78%
91% to 96%
HPV test
88% to 93% *
*Sensitivityfor CIN II
86% to 93%
Slide Objective: Highlight sensitivity and specificity for different tests
Background Information:
Once you have a test that fulfills the principles of screening and has adequate evidence of benefit, then it is important to examine the accuracy of the test to look at how well it performs. Sensitivity refers to the proportion of people with disease who have a positive test result. Specificity refers to the proportion of people without disease who have a negative test result.
In a screening program, there is repeated testing over time. Hence a single test sensitivity may be low, but with repeated program testing, it will increase.
Test characteristics of sensitivity and specificity do not prove that a screening test is efficacious. This must be shown by a demonstrated reduction in the risk of dying from the cancer with screening, the best evidence being from randomized controlled trials.
Note that FOBT sensitivity is similar to liquid-based cytology Pap testing, which is widely accepted for cervical screening. The program is currently assessing the feasibility of switching from guaiac-based FOBT (gFOBT) to fecal immunochemical testing (FIT).
References:
Nelson HD, Tyne K, Naik A, Bougatsos C, Chan BK, Humphrey L. Screening for breast cancer: an update for the U.S. Preventive Services Task Force. Ann Intern Med Nov 17;151(10):727-37, W237–42.
Rabeneck L, Zwaal C, Goodman JH, Mai V, Zamkanei M. Cancer Care Ontario guaiac fecal occult blood test (FOBT) laboratory standards: evidentiary base and recommendations. Clin Biochem Nov;41(16-17):1289–305.
Arbyn M, Ronco G, Anttila A, Meijer CJLM, Poljak M, Ogilvie G, et al. Evidence Regarding Human Papillomavirus Testing in Secondary Prevention of Cervical Cancer. Vaccine. 2012: 30S:F88–F99.

6. Effectiveness of Screening
Cancer Site
Effectiveness of Screening
Type of Studies
Cervical
With Pap testing:
Incidence and mortality reduced by up to about 80% with regular screening
Observational studies and Global incidence data
Slide Objective: Highlight effectiveness and corresponding evidence of screening
References:
Breast:
A recent summary of evidence associated with using mammography to screen for breast cancer found a 21% reduction in breast cancer mortality in women aged 50 to 69 years.
The Canadian Task Force on Preventive Health Care. "Recommendations on Screening for Breast Cancer in Average-risk Women Aged 40–74 Years." Canadian Medical Association Journal (2011): 1991–2001.
Cervical:
World Health Organization. International Agency for Research on Cancer. IARC handbooks of cancer prevention: cervix cancer screening. Vol 10. Lyon: IARC Press;2005.
Colorectal:
Note: biennial screening” refers to FOBT followed by colonoscopy for those who test positive.
Hewitson P, Glasziou P, Watson E, Towler B, Irwig L. Cochrane systematic review of colorectal cancer screening using the fecal occult blood test (Hemoccult): an update. Am J Gastroenterol. 2008;103(6):1541–9.

7. Cervical Abnormalities
Cancer (0.015%)
Atypical Glandular Cells (0.1%)
Atypical Squamous Cells: HSIL Cannot be Excluded (0.1%)
High-Grade Squamous Intraepithelial Lesion (HSIL) (0.3%)
Low-Grade Squamous Intraepithelial Lesion (2.1%)
Atypical Squamous Cells of Undetermined Significance (2.3%)
Negative for Intraepithelial Lesion or Malignancy (95.0%)
Women (aged 20–69) Eligible for Cervical Cancer Screening
Pre-cancer lesions/
Pap abnormalities: 80,000
Slide Objective: To highlight the burden of the disease.
Background Information:
As mentioned in the Ontario Cancer Statistics 2013 slide, the end point for cervical cancer screening is cervical intraepithelial neoplasia (CIN) 2 or 3 so that cervical cancer can be prevented (the end point is not cervical cancer).
In 2008, there were 1.6 million Pap tests in Ontario. Approximately 5% were abnormal, which represents about 80,000 abnormalities per year. Proportion of Pap test results in 2008:
95.0%: negative for intraepithelial lesion or malignancy (NILM)
2.3%: atypical squamous cells of undetermined significance (ASCUS)
2.1%: low-grade squamous intraepithelial lesion (LSIL)
0.3%: high-grade squamous intraepithelial lesion (HSIL)
0.1%: atypical squamous cells, HSIL cannot be excluded (ASC-H)
0.1%: atypical glandular cells (AGC)
0.015%: squamous cell carcinoma, adenocarcinoma, other malignant neoplasms (CA)
While the focus is often on cervical cancer prevention, one must also consider the substantial burden of Pap abnormalities.
Family physicians see this burden of abnormal Pap test results in their office on a weekly basis.
References:
Invasive cervical cancer—estimates for 2012 (Canadian Cancer Statistics, 2012). Cancer Care Ontario. Ontario Cervical Screening Program 2003–2008. October 2011. 7

8. Ontario Screening Data
4/17/2017
Ontario Screening Data
65% of women aged 20 to 69 screened (2009 to 2011)
Ontario Cancer Plan provincial target is 85% participation for cervical screening
Of the 454 women diagnosed with invasive cervical cancer in 2008, 60% were under-/never-screened and 40% were screened
Slide Objective: Provide current status of cervical screening in Ontario
Background Information:
Pap test screening is well-integrated in primary care.
Participation in cervical cancer screening among eligible women falls short of the provincial target, but has been consistently improving since All CCO program participation rate targets are currently under review.
The cervical cancer screening participation rate is calculated based on women aged 20 to 69. In future years, the indicator will be calculated among women aged 21 to 69.
Most women (60%) who are diagnosed with invasive cervical cancer have either never been screened or were under-screened (last screening test was more than three years ago).
About 40% of women diagnosed with invasive cervical cancer were screened.
So despite cervical cancer screening, cytology is limited in what it can do. This is part of the reason there has been so much research on alternate tests.
Seldom-/never-screened women include newcomers to Canada, women over 50 years, Aboriginal women, and women living in poverty or of low literacy.
References:
Cancer Care Ontario, Cancer Quality Council of Ontario [Internet]. Toronto: Cancer Care Ontario; 2013 [cited August 19, 2013]. Cancer System Quality Index (CSQI). Available from:
Cancer Care Ontario. Ontario Cervical Screening Program 2003–2008. October 2011.
Note: the 2013 cervical cancer screening (Pap test) participation rate varies from the 2012 participation rates (e.g., 72% for 2008–2010 compared to 65% for 2009–2011). This is due to differing methodologies used, as well as reporting on different time periods by ICES in 2012 and the CCO Evaluation and Reporting, Cancer Screening team in 2013.

9. Cervical Cancer Causes
Persistent infection with high risk (oncogenic) types of HPV (human papillomavirus)
HPV is commonly found in sexually active men and women and transmitted through any skin to skin sexual contact
Most HPV infections are transient; about 90% will clear within 2 years
Slide Objective: Provide understanding of HPV and link to cervical cancer
Background Information:
HPV is transmitted through skin to skin intimate sexual contact, including but not limited to intercourse.
Co-factors that have been associated with cervical cancer include tobacco and exposure to second-hand smoke long-term (more than five years) use of hormonal contraception, more than five full-term pregnancies, exposure to other sexually transmitted diseases (Chlamydia trachomatis or herpes simplex virus-2 [HSV-2]), poor diet (especially low antioxidant intake) and immunosuppression, e.g., human immunodeficiency virus (HIV) organ transplant, immunosuppressive drug therapy or chemotherapy.
Some HPV infections are not clinically relevant; non-oncogenic HPV infections can show cervical cell changes, which will be detected by the Pap test.
References:
Cancer Care Ontario. Perspectives on infectious agents and cancer. Toronto: Cancer Care Ontario; 2010.
Ontario Agency for Health Protection and Promotion. Ontario burden of infectious disease study. Toronto: OAHPP/ICES; 2010.
Castellsagué, X. Natural history and epidemiology of HPV infection and cervical cancer. Gynecologic Oncology 2008; 110(3) Supplement 2: S4–S7.
Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV, et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol. 1999;189(1):12–9.
Cancer Care Ontario. Human Papillomavirus (HPV) Clinician Fact Sheet. May 2007.

10. Cervical Cancer Causes
Pap tests detect cervical cell changes that are a result of HPV infections
Some abnormal Pap tests are also a reflection of premalignant change
Other co-factors (like smoking), that are not well-understood, are also involved in oncogenesis
Slide Objective: Provide understanding of HPV and link to cervical cancer
Background Information:
HPV is transmitted through skin to skin intimate sexual contact, including but not limited to intercourse.
Co-factors that have been associated with cervical cancer include tobacco and exposure to second-hand smoke long-term (more than five years) use of hormonal contraception, more than five full-term pregnancies, exposure to other sexually transmitted diseases (Chlamydia trachomatis or herpes simplex virus-2 [HSV-2]), poor diet (especially low antioxidant intake) and immunosuppression, e.g., human immunodeficiency virus (HIV) organ transplant, immunosuppressive drug therapy or chemotherapy.
Some HPV infections are not clinically relevant; non-oncogenic HPV infections can show cervical cell changes, which will be detected by the Pap test.
References:
Cancer Care Ontario. Perspectives on infectious agents and cancer. Toronto: Cancer Care Ontario; 2010.
Ontario Agency for Health Protection and Promotion. Ontario burden of infectious disease study. Toronto: OAHPP/ICES; 2010.
Castellsagué, X. Natural history and epidemiology of HPV infection and cervical cancer. Gynecologic Oncology 2008; 110(3) Supplement 2: S4–S7.
Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV, et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol. 1999;189(1):12–9.
Cancer Care Ontario. Human Papillomavirus (HPV) Clinician Fact Sheet. May 2007.

11. Cervical Cancer Natural History
Slide Objective: To highlight that cervical cancer is a rare outcome of a persistent HPV infection
Background Information:
Early changes in the cervix precede cervical cancer, usually by many years, and can generally be detected by the Pap test long before invasive cancer develops.
HPV infection causes cervix cell changes, reflected in Pap abnormality
For most women, cells change back to normal when the infection clears.
Women are less likely to clear infections as they get older.
Cervical intraepithelial neoplasia (CIN) 1 often regresses. Moreover, approximately 40% of CIN 2 regress.
CIN 3 is less likely than lower grades of CIN to regress or resolve without treatment and is therefore a useful predictor of the risk for cervical cancer.
References:
Moscicki AB, Schiffman M, Kjar S, Villa LL. Chapter 5: Updating the natural history of HPV and anogenital cancer. Vaccine. 2006; 24(Suppl 3):S3/42–S3/51.
Castle PE, Schiffman M, Herrero R, Hildesheim A, Rodriguez AC, et al. Bratti MC, et al. A Prospective Study of Age Trends in Cervical Human Papillomavirus Acquisition and Persistence in Guanacaste, Costa Rica. J Infect Dis 2005; 191(11):1808–1816.
Holowaty P, Miller AB, Rohan T, To T. Natural history of dysplasia of the uterine cervix. J Natl Cancer Inst 1999;91:252–8.
Castle, PE, Schiffman M, Wheeler CM, Solomon D. Evidence for Frequent Regression of Cervical Intraepithelial Neoplasia-Grade 2. Obstet Gynecol January; 113(1): 18–25.
Melnikow J, Nuovo J, Willan AR, Chan BK, Howell LP. Natural history of cervical squamous intraepithelial lesions: a metaanalysis. Obstet Gynecol 1998;92:727–35.
Murphy J, Kennedy E, Dunn S, Fung Kee Fung M, Gzik D, McLachlin CM, Shier M, Paszat L. Cervical Screening. Evidence-based Series Program in Evidence-Based Care and Cancer Care Ontario. October 5, 2011.

12. HPV Vaccine
Two vaccines—bivalent (Cervarix®) and quadrivalent (Gardasil®)—prevent 2 high risk HPV types that cause 70% of cervical cancers
Injected in 3 doses over 6 months
Slide Objective: Provide overview of available vaccines and efficacy for primary prevention
Background Information:
While the vaccines are approved for use in males, broad coverage in adolescent females is the preferred strategy for cervical cancer prevention.
The vaccines are also approved for women up to age 46 (user pay of $500).
Natural infection does not result in immunity. Vaccination even after exposure will protect against subsequent infections.
Studies have found both Gardasil® and Cervarix® to be safe.
Other than a brief soreness at the injection site, participants reported few side effects.
Because vaccines contain only particles from part of the virus, infection from the vaccine is not possible.
The vaccines do not contain any preservative or antibiotics.
Gardasil® protects against infection with two high risk HPV types (16 and 18), which cause 70% or more of cervical cancers, and two low risk types (6 and 11), which cause about 90% of ano-genital warts.
Cervarix® protects against HPV types 16 and 18 only.
The duration of protection in unknown, but evidence suggests protection for up to six years.
National Advisory Committee on Immunization (NACI) 2012 HPV Vaccine Recommendations (Updated January 2012): Females
Between nine and 26 years of age:
HPV2 (Ceravix) or HPV4 (Gardasil) vaccine recommended for prevention of cervical cancer and precursors in girls and women
HPV4 vaccine recommended for prevention of vulvar, vaginal, anal cancers and precursors, and anogenital warts
Vaccination between nine and 13 years (prior to onset of sexual activity) maximizes benefit
Over the age of 26 years:
HPV2 or HPV4 vaccine may be administered to women 27 years of age and older
HPV4 vaccine immunogenicity, safety and efficacy demonstrated in women aged 24 to 45; HPV2 vaccine efficacy not demonstrated in this age group, but immunogenicity data suggest efficacy will be high
NACI 2012 HPV Vaccine Recommendations (Updated January 2012): Males
HPV4 recommended for prevention of anogenital warts, penile and anal cancer, perineal intraepithelial neoplasias and associated cancers
Men who have sex with men:
HPV4 recommended in males (nine years of age and older) who have sex with men (choice of vaccine: HPV4 only)
References:
Cancer Care Ontario. Perspectives on infectious agents and cancer. Toronto: Cancer Care Ontario; 2010.
Ontario Agency for Health Protection and Promotion. Ontario burden of infectious disease study. Toronto: OAHPP/ICES; 2010.
Smith JS, Lindsay L, Hoots B, Keys J, Franceschi S, Winer R, et al. Human papillomavirus type distribution in invasive cervical cancer and high-grade cervical lesions: a meta-analysis update. Int. J. Cancer Aug 1;121(3):621–632.
Castellsagué X, Schneider A, Kaufmann AM, Bosch FX. HPV vaccination against cervical cancer in women above 25 years of age: key considerations and current perspectives. Gynecol Oncol 2009 Dec;115(3 Suppl):S15–23. Epub 2009 Oct 12.
Public Health Agency of Canada. Canadian Communicable Disease Report. An Advisory Committee Statement (ACS). National Advisory Committee Statement on Immunization (NACI). Update on Human Papillomavirus (HPV) Vaccines. Vol. 38. January Available from:

13. HPV Vaccine Provides best protection if received prior to HPV exposure
Natural infection does not reliably result in immunity
Does not replace regular cervical cancer screening
Slide Objective: Provide overview of available vaccines and efficacy for primary prevention
Background Information:
While the vaccines are approved for use in males, broad coverage in adolescent females is the preferred strategy for cervical cancer prevention.
The vaccines are also approved for women up to age 46 (user pay of $500).
Natural infection does not result in immunity. Vaccination even after exposure will protect against subsequent infections.
Studies have found both Gardasil® and Cervarix® to be safe.
Other than a brief soreness at the injection site, participants reported few side effects.
Because vaccines contain only particles from part of the virus, infection from the vaccine is not possible.
The vaccines do not contain any preservative or antibiotics.
Gardasil® protects against infection with two high risk HPV types (16 and 18), which cause 70% or more of cervical cancers, and two low risk types (6 and 11), which cause about 90% of ano-genital warts.
Cervarix® protects against HPV types 16 and 18 only.
The duration of protection in unknown, but evidence suggests protection for up to six years.
National Advisory Committee on Immunization (NACI) 2012 HPV Vaccine Recommendations (Updated January 2012): Females
Between nine and 26 years of age:
HPV2 (Ceravix) or HPV4 (Gardasil) vaccine recommended for prevention of cervical cancer and precursors in girls and women
HPV4 vaccine recommended for prevention of vulvar, vaginal, anal cancers and precursors, and anogenital warts
Vaccination between nine and 13 years (prior to onset of sexual activity) maximizes benefit
Over the age of 26 years:
HPV2 or HPV4 vaccine may be administered to women 27 years of age and older
HPV4 vaccine immunogenicity, safety and efficacy demonstrated in women aged 24 to 45; HPV2 vaccine efficacy not demonstrated in this age group, but immunogenicity data suggest efficacy will be high
NACI 2012 HPV Vaccine Recommendations (Updated January 2012): Males
HPV4 recommended for prevention of anogenital warts, penile and anal cancer, perineal intraepithelial neoplasias and associated cancers
Men who have sex with men:
HPV4 recommended in males (nine years of age and older) who have sex with men (choice of vaccine: HPV4 only)
References:
Cancer Care Ontario. Perspectives on infectious agents and cancer. Toronto: Cancer Care Ontario; 2010.
Ontario Agency for Health Protection and Promotion. Ontario burden of infectious disease study. Toronto: OAHPP/ICES; 2010.
Smith JS, Lindsay L, Hoots B, Keys J, Franceschi S, Winer R, et al. Human papillomavirus type distribution in invasive cervical cancer and high-grade cervical lesions: a meta-analysis update. Int. J. Cancer Aug 1;121(3):621–632.
Castellsagué X, Schneider A, Kaufmann AM, Bosch FX. HPV vaccination against cervical cancer in women above 25 years of age: key considerations and current perspectives. Gynecol Oncol 2009 Dec;115(3 Suppl):S15–23. Epub 2009 Oct 12.
Public Health Agency of Canada. Canadian Communicable Disease Report. An Advisory Committee Statement (ACS). National Advisory Committee Statement on Immunization (NACI). Update on Human Papillomavirus (HPV) Vaccines. Vol. 38. January Available from:

14. Ontario HPV Vaccination Program
Publicly funded school-based immunization program for grade 8 girls
New catch-up program since September for girls in grades 9-12
59% uptake in grade 8 girls (2009/2010)
More vaccine program information at
Slide Objective: To provide an overview of Ontario’s HPV Vaccination Program
Background Information:
All provinces and territories in Canada have implemented publicly-funded HPV vaccine programs with a goal of reducing the risk that women will develop cervical cancer.
Since September 2007, the Gardasil® HPV vaccine has been offered to grade 8 females as part of the voluntary school-based immunization program.
The school-based HPV vaccination program is a ground-breaking step in women’s health.
There was only a 59% uptake of grade 8 girls.
As of September 2012, girls in grades 9 to 12 who didn't receive or didn't complete the three-dose HPV immunization in grade 8 can now receive the vaccine free of charge until the end of Grade 12. For more information about the program, see
Reference:
Wilson, SE. Coverage from Ontario Cancer’s School Based HPV vaccine program: the first 3 years. 2013; 31(5): 757–62.

15. Current Guidelines
Clear evidence for primary HPV screening with cytology triage, starting at age 30, every 5 years
Must implement within organized program
Must be publicly funded
Follow cytology-based guidelines during transition to funded HPV screening
Slide Objective: To provide overview of key points regarding updated cervical cytology screening guidelines
Background Information:
There is clear evidence for primary HPV screening (seven randomized controlled trials):
More sensitive than cytology
Should start in women aged 30 and older; older women are more likely to have persistent HPV infections of clinical significance compared to younger women who tend to have transient HPV infections
There is a lower risk of developing disease after a negative HPV result compared to a negative cytology result (better negative predictive value, or NPV). A five-year interval is safe and effective.
Women with HPV-positive results should be triaged with cytology rather than be referred directly to colposcopy. Cytology triage can identify clinically relevant HPV infections and achieve more appropriate referrals to colposcopy.
The guidelines recommended that primary HPV screening be implemented within an organized screening program and that HPV testing be publicly funded.
Long-term goal is to have HPV testing as the preferred screening test for cervical cancer.
In the short term, cytology is recommended as the primary screening tool.
The HPV test is not currently publicly funded by the ministry (user fee about $90).
CCO is working with the ministry to publicly fund the HPV test.
CCO is actively working to plan for implementation of HPV test.
Reference:
Murphy J, Kennedy E, Dunn S, Fung Kee Fung M, Gzik D, McLachlin CM, et al. Cervical Screening. Toronto (ON): Cancer Care Ontario; 2011 Oct 5. Program in Evidence-based Care Evidence-based Series No.: 15-9.

16. Comparison of 2005 and 2011Guidelines
Question
2005 Guidelines
2011 Guidelines
Initiation
Within 3 years of first vaginal sexual activity with cytology (Pap test)
Age 21
Interval after Negative Test
Annual until 3 consecutive negative cytology tests, then every 2 to 3 years
Every 3 years
Cessation
Age 70 if adequate and negative screening history in previous 10 years (≥ 3 negative tests)
No change
Management guidelines for follow-up of abnormal cytology did not change
Guidelines summary:
Slide Objective: To provide comparison of 2005 and 2011 cervical cytology screening guidelines
Background Information:
The previous guidelines recommended initiation of screening within three years of sexual activity.
The new guidelines recommend starting at age 21 for women who are or ever have been sexually active. Regardless of sexual activity, women should not be screened before age 21.
The previous guidelines recommended three annual, consecutive normal Pap tests before extending the screening interval.
The new guidelines recommend triennial screening.
There is no change to cessation. Women should be screened until age 70.

17. Screening Initiation
Start at age 21 in sexually active women (includes intercourse as well as digital and/or oral sexual activity involving the genital area with a partner of either gender)
Cervical cancer rare < 25 years and extremely rare < 21 years
10 to 15 years to develop cervical cancer
Slide Objective: Highlight age of screening initiation
Background Information:
There is lack of evidence regarding age to initiate cervical screening; guidelines recommend initiating cytology screening at age 21 in sexually active women.
Cervical cancer is extremely rare in Ontario women < 21 years (0.34 per 100,000 from 2003 to 2007). Cervical cancer is rare in women less than age 21. In the five-year period from 2005 to 2009, there were fewer than six cases in women aged 15 to 19 across the entire province.
Cervical cancer is rare in women aged 20 to 24 (1.62 per 100,000 from 2003 to 2007).
Cervical cancer takes 10 to 15 years to develop from persistent HPV infection.
Most adolescents have transient HPV infections.
The consensus in other jurisdictions is that adolescents should not be screened for cervical cancer.
In recent guideline updates, many Canadian provinces recommend initiating screening at age 21 (e.g., BC, Alberta, Saskatchewan, New Brunswick, Nova Scotia, Northwest Territories).
The American guidelines include the United States Preventive Services Task Force, American Cancer Society, American College of Obstetricians & Gynecologists.
For decades, many European countries with organized screening programs have started screening in women older than age 21. Most begin at age 25; Finland and Netherlands begin at 30.
References:
Cancer Care Ontario (Ontario Cancer Registry, 2012). Prepared by Prevention and Cancer Control (Prevention and Surveillance), 2013.
Moscicki AB, Shiboski S, Hills N et al. Regression of low-grade squamous intra-epithelial lesions in young women. Lancet. 2004, 364(9446): 1678–83.
Rogstad KE. The psychological impact of abnormal cytology and colposcopy. Br J Obstet Gynaecol. 2002;109(4):364–8.
Cancer Care Ontario. Ontario Cervical Screening Program 2003–2008 report. October 2011.
New Brunswick Cervical Cancer Prevention and Screening: Clinical Practice Guidelines. June 2011.
Moyer V. Screening for Cervical Cancer: U.S. Preventive Services Task Force Recommendation Statement. Ann Intern Med. 2012;156:880–891.
Saslow D, Solomon D, Lawson HW. American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for Clinical Pathology Screening Guidelines for the Prevention and Early Detection of Cervical Cancer. J Low Gen Tract Dis May–Jun;62(3):147–72. doi: /caac Epub 2012 Mar 14.
American College of Obstetricians and Gynecologists. Cervical Cytology Screening. Obstet Gynecol. 2009;114(6):1409–20.
Bastos J, Peleteiro B, Gouveia J, Coleman MP, Lunet N. The state of the art of cancer control in 30 European countries in Int J Cancer. 2009; 126, 2700–15.

18. STI Screening
The new guidelines for cervical screening do no affect the guidelines for STI screening
Asymptomatic sexually active females under age 25 should be screened annually for chlamydia, or more often if there are multiple partners
Slide Objective: Highlight opportunities to increase screening rates, encourage appropriate screening and decrease mortality
Background Information:
There have been advances in knowledge about HPV infection, cervical cancer screening and new screening technologies. There is an opportunity to optimize the benefits of cervical cancer screening and to reduce the associated harms.
More frequent screening increases false-positive results, which can lead to harms.
CCO is working on several initiatives to improve screening rates for under- and never-screened groups.

19. Harms of Screening Adolescents
90% will clear infection within 2 years
High rates of low-grade mostly transient and clinically inconsequential abnormalities
Unnecessary anxiety from detection, biopsies and treatment
Treatment linked to possibility of adverse future pregnancy outcomes
No protective effect with screening
Slide Objective: Highlight harms of screening adolescents
Background Information:
There are harms to screening adolescents:
~90% will clear HPV infection within 24 months without consequence to their cervical health.
High rates of low-grade cytological abnormalities that are in most cases transient and clinically inconsequential HPV infections show up as cytological abnormality.
There is unnecessary anxiety due to detection and treatment of lesions—there are also resource allocation implications in colposcopy clinics.
There is a risk of adverse future pregnancy outcomes following treatment (e.g., preterm delivery, low birth weight, premature rupture of membranes).
There is also no protective effect with screening.
References:
Moscicki AB. Cervical cytology testing in teens. Curr Opin Obstet Gynecol Oct;17(5):471–5.
Bartholomew DA. Human papillomavirus infection in adolescents: a rational approach. Adolesc Med Clin Oct;15(3):569–95.
Moscicki AB, Shiboski S, Hills N et al. Regression of low-grade squamous intra-epithelial lesions in young women. Lancet. 2004, 364(9446): 1678–83.
Rogstad KE. The psychological impact of abnormal cytology and colposcopy. Br J Obstet Gynaecol. 2002;109(4):364–8.
Sasieni P, Castanon A, and Cuzick J. The Impact of Cervical Screening on Young Women: A Critical Review of the Literature 2002–2009. NHS Cancer Screening Programmes Publication No 31. Sheffield; Feb 2010
Arbyn M, Kyrgiou M, Simoens C, et al. Perinatal mortality and other severe adverse pregnancy outcomes associated with treatment of cervical intraepithelial neoplasia: meta-analysis. BMJ. 2008;337:a1284. doi: /bmj.a1284.
Kyrgiou M, Koliopoulos G, Martin-Hirsch P, Arbyn M, et al. Obstetric outcomes after conservative treatment for intraepithelial or early invasive cervical lesions: systematic review and meta-analysis. Lancet. 2006;367:489–98.
Prendiville W. The treatment of CIN: what are the risks? Cytopathology. 2009;20(3):145–53.
Sasieni P, Castanon A, Cuzick J. Effectiveness of cervical screening with age: population based case-control study of prospectively recorded dataBMJ. 2009;339.
Andrae B, Kemetli L, Sparen P, Silfverdal L, et al. Screening-Preventable Cervical Cancer Risks: Evidence From a Nationwide Audit in Sweden. J Natl Cancer Inst. 2008;100(9):622–9.
Crocetti E, Battisti L, Betta A, Palma PD, et al. The cytological screening turned out effective also for adenocarcinoma: a population-based case–control study in Trento, Italy. Eur J Cancer Prev. 2007;16(6):564–7.

20. Screening Interval
Cytology screening every 3 years unless immunocompromised or previously treated for dysplasia
No incremental benefit of screening more frequently than every 3 years
Aligns with other jurisdictions
Slide Objective: Highlight screening interval and the evidence that there is little benefit in screening more frequently than every three years
Background Information:
There is no benefit to annual cytology screening.
The new interval aligns with other jurisdictions:
Canadian provincial guidelines: two- to three-year intervals (after two to three normal)
American guidelines: United States Preventive Services Task Force, American Cancer Society, American College of Obstetricians and Gynecologists all recommend three years interval
European countries: most have three-year intervals; Finland and the Netherlands have five-year intervals
These guidelines do not apply to women who have been previously treated for dysplasia
Little evidence to guide us in managing these women
References:
IARC Working Group on cervical cancer screening, in Hakama M, Day NE, Miller AB (eds). Screening for Cancer of the Uterine Cervix. Lyon, IARC Scientific Publication, 1986.
Coldman A, Phillips N, Kan L, Matisic J, Benedet L, Towers L. Risk of invasive cervical cancer after Pap smears: the protective effect of multiple negatives. J Med Screen. 2005;12(1):7–11.
Sawaya GF, McConnell KJ, Kulasingam SL,et al. Risk of Cervical Cancer Associated with Extending the Interval between Cervical-Cancer Screenings. N Engl J Med. 2003;349:1501–9.
Sasieni P, Adams J, Cuzick J. Benefit of cervical screening at different ages: evidence from the UK audit of screening histories. Br J Cancer. 2003;89:88–93.
Hakama M., Miller A.B., & Day N.E. (1986). Screening for cancer of the uterine cervix. From the IARC Working Group on Cervical Cancer Screening and the UICC Project Group on the Evaluation of Screening Programmes for Cancer. IARC Sci. Publ. , 1–315.

21. Screening Cessation
Stop screening at age 70 if adequate and negative screening history
Low incidence of cancer in women who have been adequately screened
Potential discomfort of procedure
Difficulties visualizing squamocolumnar junction
Slide Objective: Highlight when screening can be discontinued
Background Information:
There is a lack of evidence for determining the age to cease cervical screening:
Discontinue at age 70 if adequate and negative screening history in previous 10 years (i.e., ≥ three negative tests)
Higher incidence rate in older Ontario women because they have not been regularly screened
Low rate of cervical cancer in older women who have been adequately screened
Ontario study found less than 1% of women with high-grade squamous intraepithelial lesion (HSIL) and negative screening history were over 70 years, thus providing a rationale for cessation of screening at this age
Potential discomfort of procedure
Difficulties with visualization of the squamocolumnar junction in older women
Aligns with most Canadian provinces, many of which recommend age 69 or 70:
Age 69: British Columbia, North West Territories, Alberta, New Brunswick, Prince Edward Island
Age 70: Nunavut, Manitoba and Ontario
American guidelines: USPSTF, ASCCP/ACS, ACOG recommend age 65 or 70
Age 65 or 70: American College of Obstetricians and Gynecologists (2009)
Age 65: United States Preventive Services Task Force (2012)
Age 65: American Cancer Society (ACS), American Society for Colposcopy & Cervical Pathology (ASCCP) and American Society for Clinical Pathology (ASCP) guidelines (2012)
European countries: most stop at age 64 or 65; some at age 60
Age 59 (Denmark) or age 60 (Finland, Ireland, the Netherlands, Sweden)
Age 64 (Belgium, England, Italy, Portugal) or 65 (France, Hungary, Spain)
Age 69: Iceland, Norway
References:
Sasieni P, Castanon A. Call and recall cervical screening programme: Screening interval and age limits. Curr Diagn Pathol. 2006;12:114–26.
Fahs MC, Mandelblatt J, Schechter C, Muller C. Cost effectiveness of cervical cancer screening for the elderly. Ann Intern Med. 1992;117:520–7.
Colgan TJ, Clarke A, Hakh N, Seidenfeld A. Screening for Cervical Disease in Mature Women: Strategies for Improvement. Cancer Cytopathol. 2002;96(4):195–203.

22. Cervical Screening Participation Rate
Ontario Cancer Plan target 2010: 85%
Slide Objective: Shows the age-adjusted percentage of women (aged 20 to 69) who had a Pap test within three-year time intervals (2000 to 2011), reported in CSQI 2013
Background Information:
In 2009–2011, approximately 2,761,000 (65%) Ontario women 20 to 69 years old were screened for cervical cancer with a Pap test out of 4,254,000 who were eligible for screening. In the past four reporting periods ( through 2009–2011), the participation rate steadily increased from 62% to 65% but falls short of the 85% target.
2000–2002: 62%
2003–2005: 63%
2006–2008: 64%
2009–2011: 65%
Even this small increase in screening participation is statistically significant because so many women are represented.
In the 2000–2002 period, 3.6 million women in Ontario were screened, which then increased by approximately 600,000 to 4.2 million women in the 2009–2011 period.
Report Date: January, 2013
Data Source: OHIP's CHDB; Pap tests and hysterectomy claims, CytoBase; Pap tests, OCR; resolved invasive cervical cancers, PIMS; invasive cervical cancers, CPDB; physician PEM status, CAPE; physician/patient rostering information, RPDB; demographics, PCCF+ version 5k
Prepared by: Evaluation and Reporting, Cancer Screening, Cancer Care Ontario
Note: the 2013 cervical cancer screening (Pap test) participation rate varies from the 2012 participation rates (e.g., 72% for 2008–2010 compared to 65% for 2009–2011). This is due to differing methodologies used, as well as reporting on different time periods by ICES in 2012 and the CCO Evaluation and Reporting, Cancer Screening team in 2013.

23. Cervical Screening Participation Rate by Age
Ontario Cancer Plan target 2010: 85%
Slide Objective: This additional cervical screening participation slide shows the percentage of women (aged 20 to 69) who had a Pap test within a three-year time interval, by age group (2000 to 2011), reported in CSQI 2013
Background Information:
In 2009–2011, the participation rate was highest (69%) for women aged 30 to 39 and lowest (53%) for the oldest age group (60 to 69 years old). The same pattern can be seen in earlier time periods.
The participation rate in each age group increased between 2000–2002 and 2009–2011 with the exception of the youngest age group (20 to 29 years old) (-2%).
Note: the 2013 cervical cancer screening (Pap test) participation rate varies from the 2012 participation rates (e.g., 72% for 2008–2010 compared to 65% for 2009–2011). This is due to differing methodologies used, as well as reporting on different time periods by ICES in 2012 and the CCO Evaluation and Reporting, Cancer Screening team in 2013.
Report Date: January, 2013
Data Source: OHIP's CHDB; Pap tests and hysterectomy claims, CytoBase; Pap tests, OCR; resolved invasive cervical cancers, PIMS; invasive cervical cancers, CPDB; physician PEM status, CAPE; physician/patient rostering information, RPDB; demographics, PCCF+ version 5k
Prepared by: Evaluation and Reporting, Cancer Screening, Cancer Care Ontario

24. Cervical Screening Participation Rate by LHIN
Ontario Cancer Plan target 2010: 85%
Slide Objective: This additional cervical screening participation slide shows the age-adjusted percentage of women (aged 20 to 69) who had a Pap test within a three-year time interval, by Local Health Integration Network (LHIN) (2000 to 2011) reported by CSQI 2013
Background Information:
In 2009–2011, LHIN-specific participation rates varied between 61% and 69%.
Almost all LHINs improved on their participation rates between 2006–2008 and 2009–2011.
In 2009–2011, LHINs with the highest participation rates included South East (69%), Champlain (69%) and Waterloo Wellington (67%). The Toronto Central LHIN had the lowest participation rate in 2009–2011 at 61%.
All LHINs improved on their cervical screening participation rates between 2000–2002 and 2009–2011. LHINs that showed the greatest improvement during this time included Erie St. Clair (+8%), South West (+6%) and Hamilton Niagara Haldimand Brant (+6%).
Report Date: January, 2013
Data Source: OHIP's CHDB; Pap tests and hysterectomy claims, CytoBase; Pap tests, OCR; resolved invasive cervical cancers, PIMS; invasive cervical cancers, CPDB; physician PEM status, CAPE; physician/patient rostering information, RPDB; demographics, PCCF+ version 5k
Prepared by: Evaluation and Reporting, Cancer Screening, Cancer Care Ontario
Note: the 2013 cervical cancer screening (Pap test) participation rate varies from the 2012 participation rates (e.g., 72% for 2008–2010 compared to 65% for 2009–2011). This is due to differing methodologies used, as well as reporting on different time periods by ICES in 2012 and the CCO Evaluation and Reporting, Cancer Screening team in 2013.

25. Colposcopy Rate Following a High-Grade Abnormal Pap Test at 6 Months
Slide Objective: Shows the percentage of women (aged 20 to 69) with a high-grade abnormality on a Pap test who received a colposcopy within six months or definitive treatment within six months of the high-grade abnormal screen date, by LHIN (2008–2011) reported in CSQI 2013
Background Information:
In 2011, approximately 5,000 Ontario women had a follow-up procedure within six months of a high-grade abnormal Pap test, similar to the year before.
The rate of follow-up remained steady at 81% to 82% from 2010–2011; however, the 2011 rate was higher than that of 2008 (81% vs. 79%).
In 2011, Local Health Integration Network (LHINs) across the province showed follow-up rates ranging from 68% to 87%. Five out of 14 LHINs improved their follow-up rates between 2010 and 2011, while the remaining decreased.
In 2011, LHINs with the highest follow-up rates included South East (87%), Central East (86%) and Toronto Central (85%). The Erie St. Clair LHIN had the lowest follow-up rate in 2011 at 68%.
LHINs that showed the greatest improvements in their follow-up rates from 2008–2011 were Erie St. Clair (7%), South East (6%) and North Simcoe Muskoka (6%).
This data is not shown here, but it is available on
Report Date: January, 2013
Data Source: OHIP's CHDB; Pap tests and hysterectomy claims, CytoBase; Pap tests, OCR; resolved invasive cervical cancers, PIMS; invasive cervical cancers, CPDB; physician PEM status, CAPE; physician/patient rostering information, RPDB; demographics, PCCF+ version 5k
Prepared by: Evaluation and Reporting, Cancer Screening, Cancer Care Ontario

26. Challenges
Cervical cancer screening often linked to periodic health exam, hormonal contraception and bimanual exam
Difficult for physicians/providers to track 3- year screening interval
Roll-out of program correspondence started in 2013
Slide Objective: Highlight current challenges related to cervical screening in Ontario and the updated guidelines
Background Information:
Cervical cancer screening is often linked to the periodic health exam, hormonal contraception and bimanual exam.
Hormonal contraception and bimanual exams are often associated with younger women.
The impact is that there is decreased screening in older women (age 60+).
Clinical practice has been influenced by the fact that cervical cancer screening has not been organized in Ontario.
In 2013, transitioning from opportunistic screening conducted by a primary care provider when a woman visits for a periodic health exam and/or to renew hormonal contraception prescriptions to an organized program that will support providers to moving to three-year screening intervals. This will include program correspondence (result, invitation, reminder and recall letters) to women.
In our efforts “to abstain from doing harm,” it is important to ensure that patients are appropriately screened in accordance with the evidence so that screening for cervical cancer is beneficial to the patient and minimizes harms. Cancer Care Ontario is working with the Ministry of Health and Long-Term Care to align physician incentives with evidence-based guidelines. In addition, the ministry recently introduced changes to the Schedule of Benefits, including new and revised codes. These changes largely align with Cancer Care Ontario’s guidelines for cervical cancer screening. Cumulative Preventive Care Bonuses will align with CCO’s screening guideline recommendations of triennial screening in the 2013/14 bonus year.

27. CCO Initiatives Underway
Phased correspondence to women started in Fall of 2013
Privacy notification
Result (normal, abnormal, unsatisfactory) letters
Followed by recalls and invitations
Slide Objective: Highlight the plan for CCO correspondence to women
Correspondence to Women:
Starting with results letters:
The program has started to send privacy notifications to women who have had a recent Pap test. The letter will inform them about CS programs and states how CCO collects their personal health information, how that information is used and how CCO protects their privacy. Women may opt out of the correspondence if they choose at any time.
Thirty days following the privacy notifications, results letters will be sent to women with abnormal or unsatisfactory Pap test results. This information will not be sent to women who have opted out of receiving correspondence.
Invitations and recalls to follow:
Invite women ages 30 to 69 who were last screened for cervical cancer more than three years ago.
Remind women when they are overdue for follow-up of their abnormal screening results.
Recall women at three-year intervals before they are due for screening.

28. Opportunities Updated guidelines reflect new evidence
Increase awareness of balance between benefits and potential harms of screening
Reduce interventions in young women whose abnormal Pap tests are due to transient and inconsequential HPV infections
Increase screening rates for under-/never- screened groups
Slide Objective: Highlight opportunities to increase screening rates, encourage appropriate screening and decrease mortality
Background Information:
There have been advances in knowledge about HPV infection, cervical cancer screening and new screening technologies. There is an opportunity to optimize the benefits of cervical cancer screening and to reduce the associated harms.
More frequent screening increases false-positive results, which can lead to harms.
CCO is working on several initiatives to improve screening rates for under- and never-screened groups.

29. Opportunities
Improve appropriate follow-up after abnormal Pap test result
Continue to encourage primary prevention through HPV immunization
CCO and Public Health Ontario evaluating impact of primary and secondary prevention of HPV-related disease
Slide Objective: Highlight opportunities to increase screening rates, encourage appropriate screening and decrease mortality
Background Information:
CSQI 2013 reported that the overall rate of colposcopy following a high-grade abnormal Pap test at six months was 81% in 2011.
It is important to ensure women with high-grade abnormalities receive appropriate and timely follow-up.
Cervical cancer is almost entirely preventable with screening and HPV immunization.
HPV immunization protects against the two oncogenic types of HPV that cause 70% of cervical cancers (HPV types 16 and 18).
CCO encourages primary prevention of cervical cancer through HPV immunization.
Evaluation of primary and secondary prevention of HPV-related disease is underway.
Ontario HPV Program Evaluation Committee (OHPEC) will oversee the first comprehensive provincial evaluation of the HPV vaccination program and the OCSP.
Public Health Ontario is leading the overall evaluation, as well as the HPV vaccination program evaluation, in close collaboration with the MOHLTC.
CCO is leading the secondary prevention and cervical cancer screening evaluation.

30. Screening: Future State
Clear evidence for primary HPV screening
Must be implemented within an organized program
HPV test must be publicly funded
Updated cytology guidelines to bridge transition
Slide Objective: Highlight future direction of cervical screening
Background Information:
There is clear evidence for primary HPV screening, but until the HPV test is funded, it will not be used for primary screening.
Updated cytology guidelines will help bridge the transition.
HPV testing requires detecting HPV (DNA or RNA) within cells collected from the cervix. In terms of the patient experience, testing for HPV will be much the same as performing the Pap test.

31. Future Considerations
CCO working with ministry regarding implementation of primary HPV screening
Public funding of HPV test
Family physician/primary care provider education/information
Laboratories
Organization of colposcopy services
Slide Objective: Highlight considerations for primary HPV screening
Background Information:
Public funding of HPV test:
Need to conduct economic analysis/modeling, pilot testing, etc. to plan for HPV testing as primary screen
Develop a business case to the ministry to ask them to fund HPV test as primary screen
Primary care provider education/information:
Will need to inform providers about the new screening paradigm
Provide information about how to collect sample for HPV test (i.e., largely the same collection procedure as for Pap test)
Information about the management algorithm
Support to counsel patients with HPV-positive results, cytology results and next steps
Laboratories:
Labs would be changing from primary screening with cytology to primary HPV test with cytology triage
Cytology volumes would decrease dramatically
Huge impact on workforce and laboratory processes
Colposcopy:
Studies have shown that the colposcopy referral rate increases initially with primary HPV screening and then colposcopy referral rate decreases back to baseline by the second screening round
This increase in referrals will impact capacity of the colposcopy system

32. Clinical Case Study 1
A 17-year-old old female sees you to initiate birth control pill
She started having unprotected intercourse 2 months ago
Do you screen her for
cervical cancer?
Slide Objective: Provides opportunity to engage audience in discussion on when cervical screening should be initiated
Answer:
You would not screen her for cervical cancer until she is 21 years old because teens have high rates of transient and inconsequential infections.
The harms outweigh the benefits of screening.
Discuss HPV immunization; even though it’s best when given before exposure to HPV, it can still provide a benefit despite the fact that she’s already been sexually active.
You may want to assess her risk for sexually transmitted infections (STIs), counsel her about safe sex and screen her for STIs.
You may want to counsel her about her contraceptive choices.

33. Clinical Case Study 2
A 69-year-old female had a normal Pap test when she was 59 years old, an abnormal test when she was 63 years old and a normal Pap test most recently when she was 66
At what age can she safely
stop screening?
Slide Objective: Provides opportunity to engage audience in discussion on the discontinuation of screening
Answer:
Screening can be discontinued at age 70 if there in an adequate and negative cytology screening history in the previous 10 years (i.e., three or more negative cytology tests).
Two criteria must be met in order to stop screening for cervical cancer:
Adequate: she’s been regularly screened in the previous 10 years
Negative: three consecutive normal Pap tests results in previous 10 years (negative)
She has been adequately screened, so she meets the first criterion.
However, she doesn’t meet the second criterion of having three consecutive negative Pap tests in the previous 10 years.
Therefore, she should be screened again at age 69 and again at age 72.
If her Pap tests are normal when she is screened at age 69 and age 72, then she may safely stop screening.
Otherwise, she must be screened every three years until she has three consecutive normal/negative Pap tests.

34. Cervical Cancer Resources
For more information:
Slide Objective: Highlight ColonCancerCheck resources available for primary care providers
References:
Clinical resources can be found at:
ColonCancerCheck 2010 Program Report can be found at:
FOBT patient instruction sheet and the Tip Sheet (tips for your patients to ensure FOBT results are accurate and to avoid having to repeat the test) available in English, French and 28 other languages can be downloaded from the CCC website at

35. Questions?
Thank You