A Pooled Analysis to Compare the Clinical Characteristics of Human Papillomavirus-positive and -Negative Cervical Precancers.

Abstract

Given that high-risk human papillomavirus (HPV) is the necessary cause of virtually all cervical cancer, the clinical meaning of HPV-negative cervical precancer is unknown. We, therefore, conducted a literature search in Ovid MEDLINE, PubMed Central, and Google Scholar to identify English-language studies in which (i) HPV-negative and -positive, histologically confirmed cervical intraepithelial neoplasia grade 2 or more severe diagnoses (CIN2+) were detected and (ii) summarized statistics or deidentified individual data were available to summarize proportions of biomarkers indicating risk of cancer. Nineteen studies including 3,089 (91.0%) HPV-positive and 307 (9.0%) HPV-negative CIN2+ were analyzed. HPV-positive CIN2+ (vs. HPV-negative CIN2+) was more likely to test positive for biomarkers linked to cancer risk: a study diagnosis of CIN3+ (vs. CIN2; 18 studies; 0.56 vs. 0.24; P < 0.001) preceding high-grade squamous intraepithelial lesion cytology (15 studies; 0.54 vs. 0.10; P < 0.001); and high-grade colposcopic impression (13 studies; 0.30 vs. 0.18; P = 0.03). HPV-negative CIN2+ was more likely to test positive for low-risk HPV genotypes than HPV-positive CIN2+ (P < 0.001). HPV-negative CIN2+ appears to have lower cancer risk than HPV-positive CIN2+. Clinical studies of human high-risk HPV testing for screening to prevent cervical cancer may refer samples of HPV test-negative women for disease ascertainment to correct verification bias in the estimates of clinical performance. However, verification bias adjustment of the clinical performance of HPV testing may overcorrect/underestimate its clinical performance to detect truly precancerous abnormalities.

• Authors: Philip E Castle, Amanda J Pierz, Rachael Adcock, Shagufta Aslam, Partha S Basu, Jerome L Belinson, Jack Cuzick, Mariam El-Zein, Catterina Ferreccio, Cynthia Firnhaber, Eduardo L Franco, Patti E Gravitt, Sandra D Isidean, John Lin, Salaheddin M Mahmud, Joseph Monsonego, Richard Muwonge, Samuel Ratnam, Mahboobeh Safaeian, Mark Schiffman, Jennifer S Smith, Avril Swarts, Thomas C Wright, Vanessa Van De Wyngard, Long Fu Xi
• Journal: Cancer prevention research (Philadelphia, Pa.) (Cancer Prev Res (Phila)) Vol. 13 Issue 10 Pg. 829-840 (10 2020) ISSN: 1940-6215 [Electronic] United States
• PMID: 32655005 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: ©2020 American Association for Cancer Research.

Topics

• Adult
• Early Detection of Cancer (methods)
• Female
• Global Health
• Humans
• Meta-Analysis as Topic
• Papillomaviridae (isolation & purification)
• Papillomavirus Infections (complications, virology)
• Precancerous Conditions (diagnosis, epidemiology, virology)
• Prognosis
• Uterine Cervical Neoplasms (diagnosis, epidemiology, virology)
• Uterine Cervical Dysplasia (diagnosis, epidemiology, virology)