Kye-Hyun Nam

Factors associated with HPV persistence after conization in patients with negative margins.

OBJECTIVE The clearance rate of human papillomavirus (HPV) after conization is generally high, although some HPV infections persist. We investigated the factors that affect the clearance of HPV after conization in patients with negative margins. METHODS We retrospectively analyzed 77 patients (mean age 39.9 years, range 25 to 51 years) with CIN 2/3 who underwent loop electrosurgical excision procedure (LEEP) conization with negative margins. All patients had a Pap smear and high-risk (HR) HPV testing using Hybrid Capture II system and HPV DNA chip before conization. We used>/=1 relative light units (RLUs) as the cutoff for persistence of HPV after conization. RESULTS High-risk HPV was detected in 73 of 77 (94.8%) patients before conization. At the 6-months follow-up, the high-risk HPV was eliminated in 60 of 73 (82.2%) patients. The HPV persistence rate after conization was 17.8% (13/73). Univariate analysis showed that persistent HPV infection after conization with negative margins was more likely to occur when the pretreatment viral load was high (RLU/positive control >100 (p=0.027) and the HPV was type 16 (p=0.021). Logistic regression analysis showed that preoperative HPV type 16 infection was the only significant independent factor (p=0.021) for HPV persistence out of age, cytology, punch biopsy histology, HPV viral load, and conization histology. CONCLUSION Conization effectively removes HR-HPV infection. HPV type 16 infection before conization was significantly related to HR-HPV persistence after conization with negative margins. Therefore, patients with HPV 16 infection before conization need to be followed closely.

Early human papillomavirus testing predicts residual/ recurrent disease after LEEP

Objective The purpose of this study was to determine the predictive factors for residual/recurrent disease and to analyze the timing for Pap smears and human papillomavirus (HPV) testing during follow-up after loop electrosurgical excision procedure (LEEP) for cervical intraepithelial neoplasia (CIN) 2 or worse. Methods We retrospectively analyzed 183 patients (mean age, 39.3 years) with CIN 2/3 who were treated with LEEP. Post-LEEP follow-up was performed by Pap smear and HPV hybrid capture2 (HC2) testing. The definition of persistent/recurrent disease was biopsy-proven CIN 2 or worse. Results Among 183 patients, punch biopsies were CIN 2 in 31 (16.9%) and CIN 3 in 152 (83.1%). HPV HC2 tests before LEEP were positive in 170 (95.5%) of 178 patients. During follow-up, 12 patients (6.6%) had residual/recurrent CIN 2+. LEEP margin status was a significant predictive factor for persistent/recurrent disease. Other factors such as age, HPV HC2 viral load (≥100 relative light units), and HPV typing (type 16/18 vs. other types) did not predict recurrence. Early HPV HC2 testing at 3 months after LEEP detected all cases of residual/recurrent disease. The sensitivity and negative predictive value of the HPV HC2 test for residual/recurrent disease were both 100% at 3 and 6 months. Conclusion Margin involvement in conization specimens was a significant factor predicting residual/recurrent disease after LEEP. HPV test results at 3 and 6 months after treatment were comparable. Early 3-month follow-up testing after LEEP can offer timely information about residual/recurrent disease and alleviate patient anxiety early about treatment failure.

Human papillomavirus type 16 causes larger colposcopic lesions than other HPV types in patients with grade 3 cervical intraepithelial neoplasia.

Objective Recent studies have shown that human papillomavirus (HPV) type 16 causes more definite visual abnormalities on cervigram than other HPV types and is thus easier to evaluate colposcopically. We examined factors, including HPV-16, related to colposcopic lesions in patients with grade 3 cervical intraepithelial neoplasia (CIN 3). Methods A retrospective chart review included 108 women with CIN 3 who underwent the loop electrosurgical excision procedure (LEEP). Lesions were assessed according to the number of cervical quadrant(s) involved by colposcopy, dichotomized as 2 or fewer or 3 or more quadrants involved. The Hybrid Capture 2 (HC2) test and HPV DNA chip assay (MyGene Co, Seoul, Korea) were used to detect HPV before punch biopsy or loop electrosurgical excision procedure. The type of HPV was dichotomized as HPV-16 or other (including negative cases). The HC2 viral load cutoff was 300 relative light units. Cytology was dichotomized as (1) low grade, less than, or equal to low-grade squamous lesions; or (2) high-grade, with high-grade squamous lesions or worse. Age and menopausal status were also assessed. Results The mean (SD) age of the 108 women was 41.9 (10.7) years (range = 22–76 y). Seventy-one (65.7%) had lesions involving 2 quadrants or fewer and 37 (34.3%) had lesions involving 3 quadrants or more. Multiple logistic regression revealed that larger lesions (≥3 quadrants involved) were significantly associated with HPV-16 (p = .032, odds ratio [OR] = 2.552, 95% confidence interval = 1.085–6.000) but not with age, menopausal status, cytologic grade, or HPV HC2 viral load. Conclusions Our data suggest that colposcopic lesions differ according to HPV type and that HPV-16 is associated with larger lesions, facilitating lesion detection by colposcopy.

Random biopsy after colposcopy-directed biopsy improves the diagnosis of cervical intraepithelial neoplasia grade 2 or worse.

Objectives. To evaluate the usefulness of additional random biopsies in the diagnosis of cervical intraepithelial neoplasia grade 2 (CIN 2) or worse (CIN 2+) after colposcopy-directed biopsy. Materials and Methods. A retrospective chart review was performed in 107 women with satisfactory colposcopy results after colposcopy-directed biopsy with random biopsy for abnormal cervical cytological evaluation at Soonchunhyang University Hospital between April 2008 and November 2009. Random biopsies were performed at the cervical squamocolumnar junction in lesion-free quadrants of the cervix. Loop electrosurgical excision procedure conizations were performed in 59 women. Age, referral cytology, lesion size, human papilloma virus (HPV) viral load, and HPV type were analyzed as possible indicators of lesion severity detected using random biopsy. Results. The mean age was 39.3 years (range = 21-72 y), and 96 (89.7%) women were premenopausal. Sixty-three women had CIN 2+; of those, 8 (12.7%) were diagnosed using random biopsies: 6 had high-grade squamous intraepithelial lesions; 1 had low-grade squamous intraepithelial lesions; and 1 had atypical squamous cells of undetermined significance. Lesions diagnosed as CIN 2+ using random biopsies were significantly correlated with high-grade cytology (p <.001) and lesion size (p <.001) but not age (cutoff = 40 years), HPV viral load (cutoff = 300 relative light units; Hybrid Capture 2), or HPV genotype. Of 59 patients who underwent loop electrosurgical excision procedure conization, the disease severity of 9 (15.3%) cases was upgraded 1 or more grades, compared with the punch biopsy results. Conclusions. The detection of CIN 2+, particularly high-grade cytological abnormalities and large lesion size, can be increased by additional random biopsies after satisfactory colposcopy. Loop electrosurgical excision procedure conization can detect lesions not detected by punch biopsy.

Protein Expression Profile using Two-Dimensional Gel Analysis in Squamous Cervical Cancer Patients

PURPOSE Screening in cervical cancer is now progressing to discover candidate genes and proteins that may serve as biological markers and that play a role in tumor progression. We examined the protein expression patterns of the squamous cell carcinoma (SCC) tissues from Korean women with using two- dimensional polyacrylamide gel electrophoresis (2-DE) and matrix assisted laser desorption/ionization-time of flight (MALDI- TOF) mass spectrometer. MATERIALS AND METHODS Normal cervix and SCC tissues were solubilized and 2-DE was performed using pH 3 approximately 10 linear IPG strips of 17 cm length. The protein expression was evaluated using PDQuest 2-D software. The differentially expressed protein spots were identified with a MALDI-TOF mass spectrometer, and the peptide mass spectra identifications were performed using the Mascot program and by searching the Swiss-prot or NCBInr databases. RESULTS A total of 35 proteins were detected in SCC. 17 proteins were up-regulated and 18 proteins were down-regulated. Among the proteins that were identified, 12 proteins (pigment epithelium derived factor, annexin A2 and A5, keratin 19 and 20, heat shock protein 27, smooth muscle protein 22 alpha, alpha-enolase, squamous cell carcinoma antigen 1 and 2, glutathione S-transferase and apolipoprotein a1) were protein previously known to be involved in tumor, and 21 proteins were newly identified in this study. CONCLUSION 2-DE offers the total protein expression profiles of SCC tissues; further characterization of these differentially expressed proteins will give a chance to identify the badly needed tumor-specific diagnostic markers for SCC.

Clinical significance of a negative loop electrosurgical excision procedure biopsy in patients with biopsy-confirmed high-grade cervical intraepithelial neoplasia.

Objective We sought to determine which clinical factors can predict this phenomenon and to better understand the clinical significance of negative loop electrosurgical excision procedure (LEEP) findings through long-term follow-up. Methods We identified 559 patients with biopsy-confirmed cervical intraepithelial neoplasia grade 2 or 3 (CIN 2, 3) who were treated by LEEP between February 2001 and December 2010. Preconization clinical characteristics, as well as high-risk human papillomavirus (hrHPV) status, were analyzed as possible predictors of an absence of a lesion in the specimen. The clinical significance of an absence of a lesion in the specimen, as well as other factors, was evaluated by Cox hazard regression analysis in terms of recurrence. Results No lesion on the LEEP specimen was found in 102 (18.2%) of 559 patients with CIN 2,3 on punch biopsy. Punch biopsy status of CIN 2, low HPV viral load (<100 relative light units [RLU]), and negative or positive HPV infection other than type 16 were significantly related to no lesion in the LEEP specimen. Postoperative HPV persistence (≥10 RLU) and same-type HPV detection were significantly related to recurrent disease of CIN 2+ (p < .001). The recurrence of patients with no lesion in LEEP did not statistically differ from that of patients with a lesion in the LEEP specimen (p = .390). Conclusions The absence of a lesion in the LEEP specimen is very common. A negative LEEP is associated with a persistence/recurrence rate similar to that of positive LEEP. We recommend that the follow-up for patients with no lesion in the LEEP specimen should be the same as that for patients with a lesion.

Pseudoaneurysm of uterine artery causing intra-abdominal and vaginal bleeding after cervical conization

Uterine arterial pseudoaneurysm is a very rare condition usually associated with postpartum hemorrhage. It almost never occurs after cervical conization; however, since ruptured pseudoaneurysm could be life threatening, we should consider the possibility of vascular injury such as pseudoaneurysm when we find a patient with vaginal bleeding after the process of surgical operation. Emergency arterial embolization is a well established therapeutic option to control the ruptured pseudoaneurysm. This is a case report of uterine arterial pseudoaneurysm causing intra-abdominal bleeding followed by cervical conization, which was successfully treated by uterine artery embolization.

Colposcopy at a turning point

For women who have abnormal Pap test results, the biopsy under colposcopic evaluation is the gold standard for determining the treatment modality. To increase the effectiveness of colposcopic communication, the International Federation for Cervical Pathology and Colposcopy (IFCPC) recently published fourth new nomenclature, aiming to create an evidence-based terminology. To increase the diagnostic accuracy of colposcopy, multiple biopsies of two or more sites are recommended. Recently, with the introduction of human papillomavirus (HPV) vaccine for cervical cancer prevention, pre-cancerous diseases caused by virus types 16 and 18 have been reduced, which is expected to reduce the number of colposcopic examinations and make colposcopic diagnosis more difficult.

Neural Axis Metastasis from Metachronous Pulmonary Basaloid Carcinoma Developed after Chemotherapy & Radiation Therapy of Uterine Cervical Carcinoma

Multiple primary or secondary malignancies after anticancer therapy were recently reported to be increasing in frequency. The authors describe a case of metachronous metastatic pulmonary basaloid carcinoma to the central nervous system that was discovered after chemotherapy and radiation therapy for cervical uterine carcinoma. Two different types of cancer developed within some interval. Theres the possibility that a secondary pulmonary neoplasm developed after the chemotherapy and radiotherapy conducted as cervical cancer treatment.