Detection of Residual/Recurrent Cervical Disease after Successful LEEP Conization: the Possible Role of mRNA-HPV Test

Roberta      Zappacosta; Manuel      Maria Ianieri; Andrea      Tinelli; Sarah      Gustapane; Chiara      D'Angelo; Daniela      Maria Pia Gatta; Serena      Capanna; Sandra      Rosini

Abstract

Background: Loop Electrosurgical Excision Procedure (LEEP) represents the mainstay technique for CIN2+ removal. The major concern in conservative treatment is to verify whether CIN eradication was complete, since incomplete excision is associated with an increased risk of cervical cancer. The histopathologic evaluation of resection margins status is far from perfect, since cervical lesions may recur in 5-15% of patients who had conisation specimens with clean margins.

Current follow-up protocol of patients treated by conisation for high grade CIN is manly based on the combination of cytology-plus- HPV-DNA testing. This approach showed high sensitivity but low specificity level in detecting recurrence. The consequence were overdiagnosis and overtreatment, especially in youngest women, in which spontaneous regression rate of CIN is substantial.

In this longitudinal study we investigated whether patient’s age, cone depth and pre-conisation HPV-load level, may be used as predictive markers for residual/recurrent CIN after conisation. Then we aimed to examined the role of E6/E7 mRNA testing during post-conization follow-up.

Methods: The study, focused on the outcome of 116 patients treated for CIN by LEEP, included three consecutive steps. Firstly, the authors analysed the prevalence of residual/recurrence disease after conization; then, they investigated which factors may influence treatment failure even when resection margins were clean; finally, they evaluated the diagnostic accuracy of E6/E7 mRNA test as predictive marker of recurrence.

Results: HPV infection was detected in 31% of patients at 6-month follow-up and in 11.2% of patients, at 24-month follow-up. Younger women showed higher rate of recurrence than older ones. The risk of residual/recurrent infection did not correlate with cone-depth. Recurrence is higher in patients with low viral load level than in those having high load levels. mRNA test showed higher specificity and positive predictive value than the combination cytology-plus-HPV-DNA test.

Conclusion: The inclusion of mRNA test within the current protocol of follow-up would efficiently and earlier predict the risk of residual/ recurrent cervical abnormalities after conisation. This molecular strategy would also reduce overtreatment, particularly in patients above 30 years of age.

Keywords: Cervical intraepithelial neoplasm, human papillomavirus, cervical cancer, mRNA-HPV, loop electrosurgical excision procedure, LEEP, genome amplification, REAL-Time PCR, CIN2+, cytology