Human Papillomavirus-16 DNA Quantitation Differentiates High-Grade Anal Neoplasia

Int J Environ Res Public Health. 2018 Aug 8;15(8):1690. doi: 10.3390/ijerph15081690.

Abstract

Background: Due to their higher rates of anal dysplasia/cancer, human immunodeficiency virus (HIV)-positive individuals are recommended to undergo anal dysplasia screening, which consists of anal cytology (AC) and high resolution anoscopy (HRA) with anal biopsy (AB) after abnormal AC result. However, AC variability limits its usefulness. Our objective was to evaluate human papillomavirus (HPV)-16 DNA quantitation as part of the screening algorithm. Methods: HPV-16 was detected in AC specimens from 75 HIV-positive participants using quantitative real-time polymerase chain reaction. AB results were available from 18/44 patients who had abnormal AC. Statistical tests included Mann-Whitney U, Kruskal-Wallis, receiver operating characteristic (ROC) analysis and Kappa coefficient tests. Results: HPV-16 copy numbers differed significantly across AC (p = 0.001) and AB grades (p = 0.009). HPV-16 ≥ 65 copies/cell predicted high-grade AB (p = 0.04). Using this cut-off in comparison to AB, it had better specificity (1.00) than AC (0.75) and specificity (0.77) than qualitative HPV-16 detection (0.38). Also, the Kappa coefficient of the cut-off (κ = 0.649) was higher than AC (κ = 0.557) and qualitative HPV-16 detection (κ = 0.258) to AB. Conclusion: Higher HPV-16 copy numbers corresponded to higher AC and AB grades, suggesting the importance of HPV burden on disease stage. Furthermore, HPV-16 ≥ 65 copies/cell distinguished high-grade disease and demonstrated better sensitivity, specificity, and agreement with AB than AC or qualitative HPV-16 detection. These results support the potential use of HPV quantitation in conjunction with AC in anal dysplasia screening.

Keywords: HIV/AIDS; HPV; MSM; anal cancer; cytology; dysplasia; human papillomavirus; men who have sex with men.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Algorithms
  • Anal Canal / pathology*
  • Anal Canal / virology
  • Anus Neoplasms / diagnosis*
  • Anus Neoplasms / pathology
  • Anus Neoplasms / virology*
  • Early Detection of Cancer
  • Female
  • Homosexuality, Male / statistics & numerical data
  • Human papillomavirus 16 / genetics*
  • Human papillomavirus 16 / isolation & purification*
  • Humans
  • Male
  • Mass Screening
  • Middle Aged
  • Neoplasm Grading*
  • Papillomavirus Infections / diagnosis
  • Papillomavirus Infections / virology*