Comparative Study of Human Papilloma Virus DNA Detection and Results of Histopathological Examination of Cervical Colposcopic Biopsy

摘要

In our study, we come to investigate the factors that may participate to false-negative colposcopic biopsy results. Patients positive for high-risk human papillomavirus (HPV) DNA with negative cervical histopathologic findings were examined between January 2004 and August 2006. Patients with atypical squamous cells of undetermined significance (ASC) in Papanicolaou smears, with positive HPV DNA results, but negative cervical histopathologic findings accounted for 4.5% of all ASC smears submitted for HPV DNA testing. We found 4% of the cases had focal HPV infection or mild dysplasia. When serial sectioning of the biopsy material were examined, we found that 31% had clinically significant lesions: HPV infection or cervical intraepithelial neoplasia (CIN) 1, 19%; CIN 2/3, 8%; and dysplasia, not otherwise specified, 3%. Of the remaining patients, follow-up revealed squamous abnormalities in 25%. About 5% of patients with positive HPV DNA results had a negative follow-up biopsy result. "False-negative" biopsies accounted for one third of cases. Introduction Epidemiologic data have long implicated a sexually transmitted agent, based specifically on the risk factors for cervical cancer, which include early age at first intercourse, multiple sexual partners, and a male partner with multiple previous sexual partners. A recent survey of gynecologic cytology reporting practices found a median reporting rate of 3.9% for atypical squamous cells of undetermined significance (ASC).[1] Although in most patients with ASC a significant lesion will not be found in subsequent examination, they require further evaluation because 5% to 10% of patients initially diagnosed with ASC actually have high-grade dysplasia.[2] Until recently, management of patients with ASC often involved colposcopic examination and cervical biopsy. [3]Human PapillomaVirus (HPV) is the known cause of the venereally transmitted vulvar condyloma accuminatum. It is also suspected to be an oncogenic agent in a variety of squamous tumors and proliferative lesions of skin and mucus membranes; however, there is mounting evidence for HPV involvement in cervical cancer. [4, 5] The strongest evidence is that HPV DNA is detected by hybridization techniques in 75 – 100% if patients with condylomas, precancerous cervical dysplasia, and invasive carcinoma. Since the mid to late 1990s, testing for HPV DNA in Pap tests has been shown to be a useful adjunct in triaging patients with ASC test results for colposcopy. It has been shown that HPV DNA testing using the Hybrid Capture II assay, or HCII (Digene, Beltsville, MD), performed better than repeated cytology in triaging patients with ASC.[4] In addition, reflex high-risk HPV DNA testing offers the same life expectancy while remaining more cost-effective than other management strategies.[5, 6]In a recent meta-analysis, it has been reported that in a small but significant number of women, no abnormalities were found by colposcopic-directed cervical biopsy after a diagnosis of ASC with positive high-risk HPV DNA testing.[4] In most cytologic-histologic correlation studies, colposcopic biopsy often is regarded as the “gold standard” on which gynecologic cytologic screening is to be judged. However, several studies have demonstrated that histologic examination is far from perfect.[7, 8] Aim of the workThe aim of this work is to try to investigate factors that may contribute to false-negative colposcopic biopsy results in positive high-risk HPV DNA results. Patients and Methods The material of this study included all recorded cases in the archive of the Medical Records Department of the Institute received in our lab from different Governorate areas and referred to Damanhour National Medical Institute Hospital (DNMI) during the period from January 2004 to August 2006.A computerized search identified patients with ASC Pap test results and positive results of reflexive high-risk HPV DNA testing during the period from January 2004 to August 2006. A