The use of molecular markers for cervical screening of women living with HIV in South Africa

AIDS. 2019 Nov 1;33(13):2035-2042. doi: 10.1097/QAD.0000000000002325.

Abstract

Objective: To determine the performance of molecular screening strategies for detection of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) in comparison with cytology screening in women living with HIV.

Design: Post-hoc analysis using data from a South African study cohort.

Methods: Cytology and human papillomavirus (HPV)-based strategies were evaluated, including single test and FAM19A4/miR124-2 methylation triage strategies. Participants underwent cytology screening and a colposcopy-directed biopsy. Valid results on cytology, HPV status, 16/18 genotyping and histology were available for 318 women. Detection of HPV and FAM19A4/miR124-2 hypermethylation was performed on DNA from cervical scrapes. Histological diagnosis of CIN3+ was used as outcome.

Results: Cytology provided highest specificity (91.6%), but lowest sensitivity (59.3%), whereas a single HPV test provided highest sensitivity (83.1%), but lowest specificity (66.4%). Combining cytology with methylation did not improve the performance compared with cytology alone: a slight increase in sensitivity was seen, at the cost of a decrease in specificity. Triage of high-risk HPV positive women with methylation increased specificity (76.1%) compared with a single HPV or cytology test, while maintaining acceptable sensitivity (72.9%). Similar performance was observed for HPV16/18 with methylation triage (sensitivity 79.7%, specificity 74.8%). The number of women needed to refer to detect one CIN3+ ranged from 1.5 (cytology) to 2.6 (single HPV test).

Conclusion: Molecular screening strategies using HPV, with or without HPV16/18 genotyping, and FAM19A4/miR124-2 methylation have higher sensitivity with an acceptable loss in specificity compared with current cytology screening and are efficient for the detection of CIN3+ in South African women living with HIV.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Colposcopy
  • Cytokines / genetics*
  • DNA Methylation
  • Female
  • HIV Infections / complications*
  • Human papillomavirus 16
  • Human papillomavirus 18
  • Humans
  • MicroRNAs / genetics*
  • Middle Aged
  • Papillomavirus Infections / genetics
  • Predictive Value of Tests
  • Risk Assessment
  • South Africa
  • Uterine Cervical Dysplasia / diagnosis*
  • Uterine Cervical Dysplasia / genetics
  • Uterine Cervical Neoplasms / diagnosis*
  • Uterine Cervical Neoplasms / genetics

Substances

  • Cytokines
  • MIRN124 microRNA, human
  • MicroRNAs
  • TAFA4 protein, human