Obstet Gynecol Sci.  2015 Mar;58(2):117-123. 10.5468/ogs.2015.58.2.117.

Impact of age on the false negative rate of human papillomavirus DNA test in patients with atypical squamous cells of undetermined significance

• Won KH
• Lee JY
• Cho HY
• Suh DH
• No JH
• Kim YB

• KMID: 2314035
• DOI: http://doi.org/10.5468/ogs.2015.58.2.117

Abstract

OBJECTIVE
Human papillomavirus (HPV) test was incorporated into the triage of lesser abnormal cervical cytologies: atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesion (LSIL). This study aimed to evaluate the impact of age on the efficacy of HPV testing in patients with lesser abnormal cervical cytologies.
METHODS
A total of 439 patients with ASCUS or LSIL were included. The association between age groups and the diagnostic performances of HPV test for high-grade cervical intraepithelial neoplasia (CIN2+) was evaluated.
RESULTS
Median age was 44 years (range, 17 to 75 years). ASCUS was more frequently observed in older patients while LSIL was more common in younger patients (P=0.002). CIN2+ was found in 11.3% (32/284) of the ASCUS patients and 12.9% (20/155) of patients with LSIL. Older patients with ASCUS showed lower HPV infection rates (P=0.025), but not LSIL (P=0.114). However, the prevalence of CIN2+ was similar between the age groups with ASCUS or LSIL. In patients with ASCUS, the false negative rate of HPV test for CIN2+ was 6.2%. The false negative rate of the HPV test became higher with increasing of the age after the age of 50 (P=0.034).
CONCLUSION
Our findings suggest that false negative rate of the HPV test for CIN2+ in ASCUS patients older than 50 years might become higher with increasing of the age. Negative HPV results in patients of the age >50 years with ASCUS should be carefully interpreted.

Keyword

Age; Atypical squamous cells of the cervix; Human papillomavirus DNA tests; Uterine cervical dysplasia

MeSH Terms

Cervical Intraepithelial Neoplasia
DNA*
Human Papillomavirus DNA Tests
Humans
Prevalence
Triage
Uterine Cervical Dysplasia
DNA

Reference

1. Melnikow J, Nuovo J, Willan AR, Chan BK, Howell LP. Natural history of cervical squamous intraepithelial lesions: a meta-analysis. Obstet Gynecol. 1998; 92:727–735.

2. Katki HA, Schiffman M, Castle PE, Fetterman B, Poitras NE, Lorey T, et al. Five-year risks of CIN 2+ and CIN 3+ among women with HPV-positive and HPV-negative LSIL Pap results. J Low Genit Tract Dis. 2013; 17:S43–S49.

3. Kulasingam SL, Kim JJ, Lawrence WF, Mandelblatt JS, Myers ER, Schiffman M, et al. Cost-effectiveness analysis based on the atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion Triage Study (ALTS). J Natl Cancer Inst. 2006; 98:92–100.

4. Kim JJ, Wright TC, Goldie SJ. Cost-effectiveness of alternative triage strategies for atypical squamous cells of undetermined significance. JAMA. 2002; 287:2382–2390.

5. Massad LS, Einstein MH, Huh WK, Katki HA, Kinney WK, Schiffman M, 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:S1–S27.

6. Katki HA, Schiffman M, Castle PE, Fetterman B, Poitras NE, Lorey T, et al. Five-year risks of CIN 3+ and cervical cancer among women with HPV testing of ASC-US Pap results. J Low Genit Tract Dis. 2013; 17:S36–S42.

7. Kim K, Kim JJ, Kim SM, No JH, Kim YB. Prevalence and determinants of high-risk human papillomavirus infection in women with high socioeconomic status in Seoul, Republic of Korea. Asian Pac J Cancer Prev. 2012; 13:269–273.

8. Sherman ME, Schiffman M, Cox JT. Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesion Triage Study Group. Effects of age and human papilloma viral load on colposcopy triage: data from the randomized Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesion Triage Study (ALTS). J Natl Cancer Inst. 2002; 94:102–107.

9. Poljak M, Brencic A, Seme K, Vince A, Marin IJ. Comparative evaluation of first- and second-generation digene hybrid capture assays for detection of human papillomaviruses associated with high or intermediate risk for cervical cancer. J Clin Microbiol. 1999; 37:796–797.

10. Ronco G, Giorgi-Rossi P, Carozzi F, Confortini M, Dalla Palma P, Del Mistro A, et al. Efficacy of human papillomavirus testing for the detection of invasive cervical cancers and cervical intraepithelial neoplasia: a randomised controlled trial. Lancet Oncol. 2010; 11:249–257.

11. Safaeian M, Solomon D, Wacholder S, Schiffman M, Castle P. Risk of precancer and follow-up management strategies for women with human papillomavirus-negative atypical squamous cells of undetermined significance. Obstet Gynecol. 2007; 109:1325–1331.

12. Budal EB, Haugland HK, Skar R, Maehle BO, Bjorge T, Vintermyr OK. HPV DNA testing improves CIN2+ risk stratification and detection of CIN2+ in delayed triage of ASCUS and LSIL: a population-based follow-up study from Western Norway. Cancer Med. 2014; 3:182–189.

13. Stoler MH, Wright TC Jr, Sharma A, Zhang G, Apple R, Wright TL, et al. The interplay of age stratification and HPV testing on the predictive value of ASC-US cytology. Results from the ATHENA HPV study. Am J Clin Pathol. 2012; 137:295–303.

14. Solomon D, Schiffman M, Tarone R;. Comparison of three management strategies for patients with atypical squamous cells of undetermined significance: baseline results from a randomized trial. J Natl Cancer Inst. 2001; 93:293–299.

15. Guo M, Hu L, Baliga M, He Z, Hughson MD. The predictive value of p16 (INK4a) and hybrid capture 2 human papillomavirus testing for high-grade cervical intraepithelial neoplasia. Am J Clin Pathol. 2004; 122:894–901.

16. De Cremoux P, Coste J, Sastre-Garau X, Thioux M, Bouillac C, Labbe S, et al. Efficiency of the hybrid capture 2 HPV DNA test in cervical cancer screening: a study by the French Society of Clinical Cytology. Am J Clin Pathol. 2003; 120:492–499.

17. Jastania R, Geddie WR, Chapman W, Boerner S. Characteristics of apparently false-negative digene hybrid capture 2 high-risk HPV DNA testing. Am J Clin Pathol. 2006; 125:223–228.

18. Schiffman M, Solomon D. Findings to date from the ASCUS-LSIL Triage Study (ALTS). Arch Pathol Lab Med. 2003; 127:946–949.