Protecting patients from cervical cancer and over-treatment

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Cervical cancer is highly preventable, yet approximately 530,000 women develop the disease each year worldwide and some 270,000 die from it unnecessarily. Recognised as one of the most common cancers in women, most cases occur in countries that have not yet established systematic screening or prevention practices.1

Over the decades, many countries have adopted the Papanicolaou test -- also known as “Pap smear” -- that uses a cervical cytology sample to screen women for the presence of abnormal cells to enable the diagnosis and treatment of precancerous lesions. This approach has helped reduce the number of women affected by, or who die from, cervical cancer by at least 80% in the last seventy years.2

Although the incidence of the disease has been greatly reduced through the Pap test, data show limitations of the test, including difficulties in detecting precancerous cells among many normal cells and the subjective interpretation of the test.3 As a consequence, up to a third of cervical cancers occur in women who have had normal Pap results.4-6   

The role of human papillomavirus (HPV) in cervical cancer

Almost all cervical cancers – more than 99%– are caused by a persistent high-risk human HPV infection. Therefore, screening for HPV can help identify women at risk. Finding disease early, before cancer develops, is an important prevention strategy.7 Not every woman who tests positive for high-risk HPV has or will develop cervical cancer. Women who test negative for HPV can be safely reassured that they are at very low risk for cervical cancer for at least 3-5 years.11 While there is no cure for an HPV infection, it is possible to stop disease progression and treat pre-cancer or cancer.7 There are also vaccines available for boys and girls and young men and women, ages 9 to 26, to protect against certain types of HPV.7

About HPV

HPV is a common virus that can be transmitted through direct skin-to-skin contact during sexual activity with an infected individual. Approximately 80% of women (and men) will have had an HPV infection by age 50.8 Men and women affected often do not show symptoms and are unaware that they may be passing it on to others.9,10 While more than 90% of all HPV infections are cleared by the body’s immune system within two years without causing any serious health problems. 11

There are more than 100 types of HPV and at least 13 are high-risk for cervical cancer.7 Seventy percent of cervical cancer cases are caused by two specific genotypes – HPV 16 and 18.11

Cervical cancer screening in transition

Screening technologies have advanced greatly since the introduction of the Pap smear in the 1940s. Innovative molecular biological testing based on HPV DNA including HPV 16/18 genotyping, as well as immunocytochemical and immunohistochemical staining to detect the biomarkers p16INK4a and Ki-67, two relevant indicators that are known to correlate with cervical pre-cancer disease progression, provide the ability to identify women with the greatest risk of developing cervical cancer,12-14  those who need immediate management due to the existence of cervical lesions, and those who can safely return to routine screening.  In a meta-analysis of more than 60,000 women, high-risk HPV testing was substantially more sensitive in detecting cervical disease than Pap cytology testing (96.1% vs. 53.0%), which was subsequently confirmed by a study that included more than 47,000 women.12,14 By finding and treating precancerous lesions early, clinicians can prevent cancer from developing.

Preventive practice is evolving in parallel with technological advancement, and medical guidelines currently vary country to country in their approaches to cervical cancer screening. In the current U.S. screening guidelines, HPV testing used in addition to a Pap test (also known as co-testing) is now preferred over a Pap test alone for women aged 30-65.15,16 The FDA also has approved the HPV primary screening test to be used as a stand-alone option.17 Also, other medical societies have provided recommendations that HPV screening alone is sufficient.18

Among other countries around the world who are considering HPV primary screening, the Netherlands was one of the first to decide to officially transition its national screening program for cervical cancer from Pap cytology testing to HPV primary screening. As HPV testing becomes integrated into primary cervical cancer screening in many countries of the world, even greater numbers of women will be protected from this disease and being over- or under-treated.

References

1. WHO, GLOBOCAN 2012. Estimated Cancer Incidence. Mortality and Prevalence Worldwide in 2012. http://globocan.iarc.fr/Pages/fact_sheets_population.aspx Last accessed December 2016
2. National Cancer Institute. Cervical Cancer Screening- for health professionals (PDQ®) Available at: http://www.cancer.gov/cancertopics/pdq/screening/cervical/HealthProfessional#Section_115. Last accessed December 2016 
3. Herbert A et al. BJOG. 2009;116(6):845-853
4. Leyden WA et al. J Natl Cancer Inst. 2005;97(9):675-683
5. Andrae B et al. J Natl Cancer Inst. 2008;100(9):622-629
6. Priest P et al. Bjog. 2006;114(4):398-407
7. WHO. Human papillomavirus (HPV) and cervical cancer http://www.who.int/mediacentre/factsheets/fs380/en/ Last accessed December 2016
8. Centers for Disease Control. Epidemiology and Prevention of Vaccine-Preventable Diseases. The Pink Book: Course Textbook - 12th Edition Second Printing (May 2012). Retrieved from http://www.cdc.gov/vaccines/pubs/pinkbook/hpv.html on March 3, 2013.
9. Kerkar SC et al. Sex Reprod Health. 2011 Jan;2(1):7-11.
10. Centers for Disease Control. Genital HPV Infection – Fact Sheet. http://www.cdc.gov/std/hpv/stdfact-hpv.htm  Last accessed December 2016
11. CDC. Human Papillomavirus. http://www.cdc.gov/vaccines/pubs/pinkbook/hpv.html Last accessed December 2016
12. Wright TC et al. Gynecol Oncol. 2015;136(2):189-197
13. Ikenberg H et al. J Natl Cancer Inst. 2013; 105(20): 1550-1557
14. Bergeron C et al. Cancer Cytopathol. 2015;123(6): 373-381
15. Cuzick J  et al. Int J Cancer. 2006;119(5):1095-1101.
16. US Preventative Services Task Force. Cervical Cancer: Screening. http://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/cervical-cancer-screening  Last accessed December 2016
17. U.S Food & Drug Administration.  http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm394773.htm. Last accessed December 2016
18. ACOG: Obstet Gynecol. 2016;127(1):e1-e20.