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Cervical cancer is characterized as a slow growing neoplasm where abnormal cells of the cervix develop into pre-cancerous cells that later become cancerous 1. It was hypothesized in 2012 that 1350 Canadian women would be diagnosed with this disease and that 390 women would die because of it <2>. Several risk factors have been associated with cervical cancer including smoking, sexual activity, and oral contraceptive use <3>. However, the most significant risk associated with the development of cervical cancer is the contraction of human papillomavirus (HPV) <3>. The Canadian Cancer Society Statistics for 2012 report that the incidence of cervical cancer has decreased by 1.4% and the mortality of this disease has decreased by 2.9% in the past year <4>. This rate of decline has been occurring for over 10 years and is likely attributed to routine Pap tests <4>. With the exciting emergence of two preventative vaccines in Canada against HPV, these rates have been hypothesized to decrease even more <4,5>.
The difference between Pap Tests and HPV DNA testing
Cervix cytology screening or a Pap test involves obtaining cervical cells and analyzing them to determine the presence abnormal cells which may be present due to contraction of HPV <6,7>. Any type of abnormal result found in the sample of cells will require follow up testing and potential treatment as directed by the patient's health care provider <6>. HPV DNA testing is performed the same way as the Pap test with a specific goal of determining if the patient is infected with strains of HPV known to cause cervical cancer <8>. Some strains of HPV known to cause genital warts are 6 and 11, while strains 16 and 18 have been known to cause cervical cancer <9>. It should be noted that an HPV infection can be asymptomatic and may resolve on its own without causing cancer <9>. Because there is still the risk of developing cancer, screening is still essential to detect abnormal cells early and prevent progression of disease <6>.
Cervical Cancer Screening Guidelines: Old vs New
Screening guidelines for cervical cancer in Ontario have changed compared to what they were in 2005. In the past it was recommended that women should undergo their first screening within three years of becoming sexually active and then every year thereafter until three tests proved negative <10>. After that point, testing was recommended to be completed every 2 or 3 years <10>. New guidelines from Cancer Care Ontario have changed the initiation time of the test, screening interval and interval cessation time as shown in Table 1 <11>.
Table 1: Cervical Cancer Screening Guidelines from Cancer Care Ontario <11>
When to begin cervical cancer screening
Begin testing for cervical cancer when women are 21 years old. These women must be or have been sexually active in the past.
When to perform the next screening
If the results of the test prove normal, the next test should be completed in 3 years.
When to stop cervical cancer screening
When women are 70 years of age and have had 3 or more negative tests in the past 10 years.
It should therefore be noted that women who are not sexually active by 21 years of age do not need to be screened <11>. It is also recommended that women who have been vaccinated against HPV still continue normal screening <11>. Special considerations should be made for women who have been treated for dysplasia or are immunocompromised and should be monitored by their physician as appropriate <11>.
The new screening guidelines are based on clinical evidence from various studies. One study referenced in the new guidelines by Sasieni et al looked at cervical cancer screening and its effect on the incidence of cervical cancer; paying particular attention to patient age <12>. This prospective case-control study found that in women ages 22-24 who were screened for cervical cancer, there was no clinical correlation of decreased prevalence of cervical cancer in women ages 25-29 (OR = 1.11 with CI 95% 0.83-1.5) <12>. The authors concluded that there was little impact on rates of cervical cancer in women up till the age of 30 as a result of screening younger women, in the 20-24 age range <12>. The Canadian Task Force on Preventative Health Care recently released cervical cancer screening guidelines in the Canadian Medical Association Journal, which also quote the above study <13>. The guidelines are similar to those of Cancer Care Ontario, stating that women under 20 years of age should not be routinely screened (a strong recommendation) <13>. The same recommendation is made for women ages 20-24 but is based on less substantial evidence <13>.
Cancer Care Ontario has also provided guidelines on further screening if the first cytology sample is positive for a variety of diagnoses <11>. Depending on the diagnosis, the next steps in care for the patient may include further cytology testing, a colposcopy, or in the case of atypical squamous cells of undetermined significance HPV testing <11>. HPV testing is not funded by the Ministry of Health and Long Term Care, despite the fact that Cancer Care Ontario has recommended it be first line in screening for cervical cancer based on several studies <10,11>. In the updated guidelines, Cancer Care Ontario reports that HPV DNA testing would begin when women are 30 years of age and that subsequent screening upon a negative test would occur every 5 years <10>. Cytology screening would only be used upon a positive HPV DNA test <10>. These new guidelines reference several randomized controlled trials (RCT) to support the use of HPV DNA testing <10>. One RCT by Mayrand et al looked at whether testing for HPV DNA is more effective than Pap tests for cervical cancer screening <14>. 10 154 women between ages 30-69 were randomly assigned to either the HPV DNA testing focused arm or the Pap test focused arm. Both tests were performed in either group, but the order of the tests were such that patients in the HPV DNA testing arm would receive that test first and vice versa <14>. The sensitivity of the HPV DNA testing arm for cervical intraepithelial neoplasia grade 2 or 3 was 94.6% (95%CI: 84.2-100) and the specificity was 94.1% (95%CI: 93.4-94.8). The sensitivity of the Pap test arm was 55.4% (95%CI: 33.6-77.2) and the specificity was 96.8% (95%CI 96.3-97.3) <14>. The authors were able to conclude that HPV testing has increased sensitivity when testing for cervical intraepithelial neoplasia <14>.
Preventative Vaccines Available: Cervarix® vs Gardasil®
Cervarix® and Gardasil® vaccines are available in Canada for prevention of HPV <5>. The vaccines, which protect against certain forms of HPV known to cause cervical cancer should be administered to females, and males in the case of Gardasil®, optimally before becoming sexually active <5>. However, both can be administered to women who have been sexually active in the past <5>. Both vaccines cover HPV strains 16 and 18 while Gardasil® also covers strains 6 and 11 <5>. Other advantages to the Gardasil® vaccine are that it is indicated in both females and males and can be administered in women up to the age of 45, an indication as per April 2011 <5>. Gardasil® has been implemented into Ontario's Routine Immunization program for girls in grade 8 <15,16>. A review article by Schiller et al looked at four phase III clinical trials involving the use of Gardasil® and Cervarix® <17>. Both vaccines proved to be effective against the HPV strains they target as well as safe for patients to use <17>. This review article also reported the efficacy of Gardasil® and Cervarix® in providing further protection against negative outcomes associated with the HPV strains which they target <17>. This included genital warts as well as specific vulva and vaginal cancers in the case of Gardasil®, and specific types of anal infections in the case of Cervarix® <17>.
The Future of Cervical Cancer Screening and Prevention
As incidence rates of cervical cancer continue to decrease due to improved screening techniques and the development of preventative HPV vaccines, it is hoped that mortality rates will significantly plummet. Health care practitioners are hoping that HPV DNA testing will soon become the standard of cervical cancer screening with further funding from the Ministry of Health and Long Term Care <10>. With the future completion of novel and innovative clinical trials such as those involving the safety of using HPV vaccines in already infected females or using folic acid in the prevention of cervical cancer, health care professionals can learn more about this disease and further improve the ways in which it is screened for and prevented <18>.