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Some hrHPV genotypes incur higher risk of precancer than others.1

Addressing the need for enhanced risk stratification

As the inclusion of HPV testing with Pap cytology for screening results in identification of more women at high risk, a new limitation is emerging — the lack of enhanced risk stratification that can identify those women who require more aggressive management.2

Current practice can involve repeating both Pap cytology and pooled hrHPV DNA testing in 12 months for women with normal cytology and a positive hrHPV DNA result instead of referring them for colposcopy. This approach, while an improvement on cytology alone in the early detection of precancer or cervical cancer, remains limited by:

  • Lack of HPV 16/18 genotype-specific results, which allows for risk stratification
  • Delays in clinical intervention for those at highest risk
  • Uncertainty and anxiety on the part of both physician and patient when the patient has normal cytology and a positive hrHPV DNA result


The Clinical Dilemma: The HPV-positive woman

Pooled hrHPV testing provides only part of the answer

An HPV-negative result provides confidence An HPV-positive result leaves questions
99% negative predictive value9 High risk of false-positives due to lack of specificity10
Long-term protective benefit of hrHPV is well proven9 False-positives have an unnecessary adverse psychosocial impact on women11
A women negative for HPV can be managed differently than a woman positive for high-risk genotypes12 Following each hrHPV-positive test result with colposcopy places a large burden on the healthcare system
The screening interval can safely be extended for HPV-negative women12 Dilemma: Inability to discern who would benefit from immediate colposcopy without further triage13

HPV 16/18 genotyping identifies women at the greatest risk of ≥CIN3.

Rate of ≥CIN3 by hrHPV status

10-year cumulative incidence rate of CIN3 by hrHPV status2

10-year Cumulative Incidence Rate of CIN3 by hrHPV Status

Women with HPV 16 and 18 are at greatest risk of developing high-grade cervical lesions2

In a seminal study of 20,810 women in the Kaiser Permanente healthcare system, in the population of women with normal cytology, those who were HPV 16 positive and those who were HPV 18 positive were shown to be at the highest risk of developing ≥CIN3.

Discover a woman’s risk for ≥CIN2.

Role of persistence of HPV genotypes in development of ≥CIN3

12-year risk of ≥CIN3 in Danish women with normal cytology and persistent hrHPV8

12-year Risk of ≥CIN3 in Danish Women with Normal Cytology and Persistent hrHPV

Women who had persistent HPV 16 infection had an approximately 50% 12-year risk of ≥CIN3.

  • Acronyms:


1. cobas® 4800 HPV Test US package insert. April 2011.

2. 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):1072-1079.

3. The American Congress of Obstetricians and Gynecologists. ACOG Practice Bulletin. Clinical Management Guidelines for Obstetrician-Gynecologists: Screening for Cervical Cancer. November, 2012.

4. Bosch FX, de Sanjosé S. Human papillomavirus and cervical cancer — burden and assessment of causality. J Natl Cancer Inst Monogr. 2003;31:3-13.

5. Bulk S, Berkhof J, Bulkmans NW, et al. Preferential risk of HPV16 for squamous cell carcinoma and of HPV18 for adenocarcinoma of the cervix compared to women with normal cytology in The Netherlands. Br J Cancer. 2006;94(1):171-175.

6. Ault KA, Joura EA, Kjær SK, et al. Adenocarcinoma in situ and associated human papillomavirus type distribution observed in two clinical trials of a quadrivalent human papillomavirus vaccine. Int J Cancer. 2011;128(6):1344-1353.

7. de Sanjosé S, Quint WG, Alemany L, et al. Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective cross-sectional worldwide study. Lancet Oncol. 2010;11(11):1048-1056.

8. Kjær SK, Frederiksen K, Munk C, Ifner T. Long-term absolute risk of cervical intraepithelial neoplasia grade 3 or worse following human papillomavirus infection: role of persistence. J Natl Cancer Inst. 2010;102(19):1478-1488.-

9. Castle PE, Stoler MH, Wright TC Jr, Sharma A, Wright TL, Behrens CM. Performance of carcinogenic human papillomavirus (HPV) testing and HPV16 or HPV18 genotyping for cervical cancer screening of women aged 25 years and older: a subanalysis of the ATHENA study [published online August 23, 2011]. Lancet Oncol. doi:10.1016/S1470-2045(11)70188- 7.

10. Saslow D, Solomon D. Lawson HW, et al. 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. Am J Clin Pathol. 2012; 137:516-542.

11. Gray NM, Sharp L, Cotton SC, et al. Psychological effects of a low-grade abnormal cervical smear test result: anxiety and associated factors. British J of Cancer. 2006;94:1253:1262.

12. Katki HA, Kinney WK, Fetterman B, et al. Cervical cancer risk for women undergoing concurrent testing for human papillomavirus and cervical cytology: a population-based study in routine clinical practice. Lancet Oncol. 2011;12(7):663- 672.

13. Cox JT, Castle PE, Behrens CM, et al. Comparison of cervical cancer screening strategies incorporating different combinations of cytology, HPV testing and genotyping for HPV 16/18: results from the ATHENA HPV study. Am J Ob Gyn. 2012:In Press.