Verrucous Carcinoma of the Cervix: Detection of Carcinogenetic Human Papillomavirus Types and their Role during Follow-up

Abstract

Background: Verrucous carcinoma is a rare variant of well-differentiated squamous cell carcinoma of the uterine cervix. Infection with high-risk human papillomavirus (HPV) is the main cause of intraepithelial and invasive neoplasias of the female genital tract, but the aetiology of verrucous carcinoma is still unknown. The aim of this study was to evaluate the presence of HPV in verrucous carcinomas of the cervix and to investigate the persistence and the role of high risk HPV types in follow-up. Patients and Methods: Three patients, with atypical cytologies, were observed. All the patients underwent cytology and colposcopy followed by direct biopsy. The Hybrid Capture II microplate method was used for molecular detection of pre-surgical low- and high-risk HPV types. HPV tests were performed during the follow-up, annually. Results: The cytological findings revealed that atypical squamous cells “cannot rule out high-grade lesion” (ASC-H) in one case and high grade squamous intraepithelial lesion (H-SIL) in two cases. The HPV test detected high risk HPV types. Colposcopic findings showed cervical exophytic lesions. The histology revealed a well-differentiated verrucous carcinoma Ib stage, according to FIGO classification, in every case. Following radical hysterectomy, the post-operative course was uneventful. The mean follow-up time was 4.6 years. The follow-up HPV tests of the H-SIL patients were consistently negative as to cytological and colposcopical findings and no relapse was observed. At one-year follow-up the ASC-H patient who had shown postoperative histological features of koilocytosis associated with CIN2 and VAIN 3 had a persistence of high-risk HPV types with negative cytological and colposcopical findings. The HPV test was positive for two years and colposcopic and histological findings of VAIN degree 2 were revealed three years after surgery. Following vaginal laser CO₂ vaporization the subsequently cytological and colposcopic checks were negative as was molecular detection of HPV. Conclusion: Follow-up colposcopy, cytology and molecular detection of HPV is recommended in all verrucous carcinoma patients since carcinogenic HPV DNA detection could represent a valuable diagnostic tool as an adjunct to cytology, for monitoring HPV infections with transforming potential.