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Multiple Intraepithelial Neoplasias of the Lower Female Genital Tract: The Reliability of HPV mRNA Test

Frega, Antonio MD1; Sesti, Francesco MD2; Sopracordevole, Francesco MD3; Biamonti, Alberto MD4; Votano, Sergio MD5; Catalano, Angelica MD1; Milazzo, Giusi Natalia MD1; Gentile, Marco MD1; Ricciardi, Enzo MD1; French, Deborah MD6; Moscarini, Massimo MD1

Journal of Lower Genital Tract Disease:
doi: 10.1097/LGT.0b013e31829706bc
Original Articles

Objective: Human papillomavirus (HPV) is the most important pathogenetic factor of intraepithelial neoplasias of the lower genital tract. HPV-DNA and mRNA tests are applied for the management of epithelial dysplasias. The aims of this multicentric retrospective study were to compare the 2 molecular tests before the onset of metachronous intraepithelial lesions and to analyze the different characteristics between synchronous and metachronous lesions and their relationship to the pathologic mechanisms.

Materials and Methods: The study concerns 55 cases of multiple intraepithelial neoplasias of the lower genital tract. Clinical features of patients with synchronous and metachronous lesions were analyzed. During a 3-year follow-up, HPV-DNA and mRNA tests were performed every 6 months after treatment of the initial lesion. HPV-DNA and mRNA results were analyzed 12 and 6 months before, at time of the onset of the metachronous lesion, and 6 months after its treatment.

Results: We observed 31 synchronous lesions and 24 metachronous lesions. Immunodeficiency and multiple genotypes were associated with the synchronous lesions (p = .04 and p = .02, respectively). During the follow-up, positive DNA and mRNA tests increased before the appearance of the metachronous lesion and decreased 6 months after; mRNA test was significantly better than the DNA test 6 months before the appearance of the lesion (p = .04) and at the time of its appearance (p = .02).

Conclusions: Our results support the hypothesis that a positive HPV-mRNA test could be a marker of persistent infection and a risk factor for the onset of metachronous lesions.

In Brief

E6/E7 proteins could be a marker of persistent infections, thus HPV-mRNA test could prove itself to be a more precise predictor of metachronous lesions.

Author Information

1Department of Gynecological, Obstetric and Urological Sciences, Sant’ Andrea Hospital, Sapienza University of Rome, Rome, Italy; 2Section of Gynecology, Academic Department of Biomedicine and Prevention and Clinical Department of Surgery, Tor Vergata University Hospital, Rome, Italy; 3Department of Gynaecologic Oncology, National Cancer Institute, Aviano, Italy; 4Department of Obstetrics and Gynaecology, Cristo Re Hospital, Rome, Italy; 5Department of Obstetrics and Gynaecology, San Carlo Hospital-IDI IRCCS, Rome, Italy; and 6Department of Clinical and Molecular Medicine, Sant’ Andrea Hospital, Sapienza University of Rome, Rome, Italy

Reprint requests to: Antonio Frega, MD, Department of Gynecological, Obstetric and Urological Sciences, Sant’ Andrea Hospital, Sapienza University of Rome, Via di Grottarossa 1035-1039, 00189 Rome, Italy. E-mail:

The authors have declared they have no conflicts of interest.

Copyright © 2014 by the American Society for Colposcopy and Cervical Pathology