Abstract
Purpose. To describe the acquisition, persistence, and clearance of HPV infection in women with CIN 2 followed up for 12 months. Methods. Thirty-seven women with CIN 2 biopsy, who have proven referral to cervical smear showing low-grade squamous intraepithelial lesions or atypical squamous cells of undetermined significance and tested for HPV, were followed up for one year with cervical smear, colposcopy, and HPV test every three months. HPV DNA was detected by the polymerase chain reaction and genotyping by reverse line blot hybridization assay. Results. CIN 2 regression rate was 49% (18/37), persistence as CIN 1 or CIN 2 was 22% (8/37), and progression to CIN 3 was 29% (11/37). Multiple HPV types were observed at admission in 41% (15/37) of cases. HPV 16 was detected at admission in 58% (11/19) of the cases that persisted/progressed and in 39% (7/18) of the cases that regressed. HPV 16 was considered possibly causal in 67% (10/15) of the cases that persisted or progressed and in 10% (1/10) of the cases that regressed (P = 0.01). Conclusion. Multiple HPV infections were frequently detected among women with CIN 2 at admission and during the followup. The CIN 2 associated with HPV 16 was more likely to persist or to progress to CIN 3.
Highlights
Cervical intraepithelial neoplasia (CIN) and cervical cancer derive from cellular transformations of the cervix epithelium after HPV infection
Women aged 18 to 46 years old were considered eligible for the study if they fulfilled the following criteria: (1) referral cervical smear showing atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesion (LSIL); (2) biopsy showing CIN 2 reviewed by senior pathologist who was unaware of the DNA HPV test results [10]; (3) lesion completely visualized by colposcopy and squamocolumnar junction totally visible; (4) not being pregnant; (5) showing no evidence of any immunodeficiency diseases; (6) no history of previous invasive neoplasia; (7) HPV test result
The cases with undefined HPV possibly causal type were not considered for the latter analysis. According to this cohort study, multiple HPV infections were frequently detected in women with CIN 2, as new HPV types were frequently detected during twelve-month followup
Summary
Cervical intraepithelial neoplasia (CIN) and cervical cancer derive from cellular transformations of the cervix epithelium after HPV infection. High-risk HPV (HR-HPV) persistent infections represent a necessary cause of cervical cancer, but not sufficient [1]. It was thought that cervical squamous cell carcinomas (SCC) would always evolve from HPV infected normal cervical epithelium via a continuum, long-lasting consecutive CIN 1, CIN 2, and CIN 3 lesions [1]. It has been shown that clinically relevant CIN 2 or CIN 3 may be induced within 2-3 years following HPV high-risk infection, and another 10–12 years may pass until invasive cervical carcinoma would develop [2]. Most CIN 1 lesions that are associated with HR-HPV, and some CIN 2 lesions, should not be considered as true precursor stages of cervical cancer but rather the cytopathic effect of a productive viral infection [3]. The development of CIN 3 arises in women who cannot resolve the HPV infection, and the infections can persist for years or decades following initial exposure [8]
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