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HPV and Cervical Cancer

Pap Cytology: Impact and Limitations

For the last 50 years, Pap cytology screening has had a tremendous impact on women’s health. Since its introduction, the use of regular Pap cytology screening, together with the diagnosis and treatment of precancerous lesions, has contributed to an 80% reduction in the incidence and mortality of cervical cancer in countries with systematic screening.1 However, even though we know cervical cancer is nearly 100% preventable with proper HPV vaccination, screening and treatment -- 311,000 women worldwide are still dying of cervical cancer each year2 and over 570,000 women are diagnosed. To reduce the incidence and mortality rates, attention must focus in part on the screening, triage and management of women found to be at risk for cervical cancer. Furthermore, the majority of cervical cancer deaths occur in low to middle income countries where the infrastructure needed to support Pap cytology does not exist. New screening solutions are necessary to increase women's access and to implement more optimal prevention strategies.

The Limits of Pap Cytology

Although Pap testing has proven to be a useful screening tool in countries with organized or opportunistic screening programs, there are limitations and drawbacks to using Pap cytology alone:

  • Limited sensitivity: Pap cytology has limited sensitivity. When used without adjunct testing, disease may be missed.3,4,5,6    

  • Subjective interpretation: Interpretations of samples are based on individual judgments of pathologists or technicians, which can compromise reproducibility. Guidelines are provided, but no definitive objective standard exists.1,7  

  • Interpretation errors: False-negative reports may occur when pathologists or technicians fail to detect abnormal cells. False-positive results may also occur when normal cells are incorrectly categorized as abnormal.1   

  • Sample quality: When samples are prepared as a smear, quality may not be sufficient to enable acceptable analysis.8

These issues can lead to over- or underestimation of risk.8,9 Overestimation of risk may lead to unnecessary tests or treatments. This can be of particular concern to younger women, who have many false-positive tests and for whom treatment for suspicious lesions may have long-term consequences for fertility and pregnancy. Underestimation of risk can result in delays or absence of action that might prevent or compromise treatment.




Normal cytology does not always mean cancer-free: Up to one-third of cervical cancers occur in women who received a normal Pap test result10,11

The Case for HPV Primary Screening

The discovery of HPV as the cause of cervical cancer has revolutionized cervical cancer prevention strategies.3,12,13  An HPV DNA test is a more sensitive indicator of risk for a woman's future cervical health than a Pap test alone.14  In fact, leading US medical societies (ACOG, ASCCP, SGO) now support HPV primary screening as an option for cervical cancer screening for women ages 25 and older.

Evidence supports high-risk HPV (hrHPV) testing for primary screening of cervical cancer:2

  • In primary screening, hrHPV testing was proven more sensitive than cytology for detecting ≥CIN2 and ≥CIN3.15
  • There is an opportunity to identify those at highest risk, since 70% of cervical cancers are caused by HPV genotypes 16 and 18.1

Multiple U.S. and International guidelines recommend HPV primary screening. Learn more

Sensitivity is vital in Primary HPV Screening

There is risk of missed disease if a clinically relevant hrHPV infection is not detected in the first round of routine screening. Women with undetected hrHPV infections may progress to cancer.

"Per U.S. guidelines every 3-5 years, many other countries follow every 5 years interval"

HPV Genotyping: Identify Women at Greatest Risk

Since HPV 16 and 18 confer a higher risk of having precancerous lesions and cervical cancer than other genotypes,17 focusing on these genotypes gives physicians useful details upon which to make effective treatment decisions. Distinguishing HPV 16 and 18 from other high-risk HPV types may identify women at the greatest risk of ≥CIN317 and those that would benefit from colposcopy.

 

Be confident with cobas® HPV Test

Screen Confidently 

Women with a positive high-risk HPV result may benefit from a biomarker-based triage test that can be run from the same sample collected for HPV DNA screening or Pap cytology. Immediate triage can give more information sooner, to help guide next step clinical decisions. 

Click here to learn more about CINtec® PLUS Cytology.

 

References

  1. National Cancer Institute. Cervical Cancer Screening (PDQ®). https://www.cancer.gov/types/cervical/hp/cervical-screening-pdq (accessed 29April2020)
  2. Cancer Today, International Agency for Research in Cancer (IARC) GLOBOCAN 2018 Registry: https://gco.iarc.fr/today/data/factsheets/cancers/23-Cervix-uteri-fact-sheet.pdf (accessed 29April2020)
  3. Saslow D, Solomon D, Lawson HW, et al; for the ACS-ASCCP-ASCP Cervical Cancer Guideline Committee. 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. CA Cancer J Clin. 2012;62:147-172.
  4. Barcelos AC, Michelin MA, Adad SJ, Murta EF. Atypical squamous cells of undetermined significance: Bethesda classification and association with Human Papillomavirus. Infect Dis Obstet Gynecol. Epub 2011 Jun 29.
  5. Andrae B, Kemetli L, Sparén P, et al. Screening-preventable cervical cancer risks: evidence from a nationwide audit in Sweden. J Natl Cancer Inst. 2008;100(9):622-629.
  6. Leyden WA, Manos MM, Geiger AM, et al. Cervical cancer in women with comprehensive health care access: attributable factors in the screening process. J Natl Cancer Inst. 2005;97(9):675-683.
  7. Galgano MT, Castle PE, Atkins KA, et al. Using biomarkers as objective standards in the diagnosis of cervical biopsies. Am J Surg Pathol. 2010;34(8):1077-1087.
  8. Solomon D, Davey D, Kurman R, et al. The 2001 Bethesda System: terminology for reporting results of cervical cytology. Journ Am Med Assoc. 2002;287(16):2114-2119.
  9. Massad LS, Einstein MH, Huh WK, et al. 2012 updated consensus guidelines for the management of abnormal cervical cancer screening tests and cancer precursors. J Low Genit Tract Dis. 2013;17(Suppl 1):S1-S27.
  10. Leyden WA, Manos MM, Geiger AM, et al. Cervical cancer in women with comprehensive health care access: attributable factors in the screening process. J Natl Cancer Inst. 2005;97(9):675-683.
  11. Andrae B, Kemetli L, Sparén P, et al. Screening-preventable cervical cancer risks: evidence from a nationwide audit in Sweden. J Natl Cancer Inst. 2008;100(9):622-629.
  12. Rijkaart DC, Berkhof J, Rozendaal L, et al. Human papillomavirus testing for the detection for high-grade cervical intraepithelial neoplasia and cancer: final results of the POBASCAM randomized controlled trial. Lancet Oncol. 2012; 13:78-88.
  13. Bosch FX, de Sanjosé S. Chapter 1: Human papillomavirus and cervical cancer—burden and assessment of causality. J Natl Cancer Inst Monogr. 2003;31:3-13.
  14. Wright, T. C., et al. Gynecol Oncol. 2015; 136(2): 189-19
  15. Whitlock EP, Vesco KK, Eder M, Lin JS, Senger CA, Burda BU. Liquid-based cytology and human papillomavirus testing to screen for cervical cancer: a systematic review for the U.S. Preventative Services Task Force. Ann Intern Med. 2011; 155:687-697.
  16. Khan MJ, Castle PE, Lorincz AT, et al. The elevated 10-year risk of cervical precancer and cancer in women with human papillomavirus (HPV) type 16 or 18 and the possible utility of type-specific HPV testing in clinical practice. J Natl Cancer Inst. 2005;97(14):1072-107
  17. Perkins RB, et al. 2019 ASCCP Risk-Based Management Consensus Guidelines for Abnormal Cervical Cancer Screening Tests and Cancer Precursors. J Low Genit Tract Dis. 2020;24(2):102-31.