Sang Soo Seo

Incidence of cervical, endometrial, and ovarian cancer in Korea, 1999-2010

Objective To investigate the recent incidence of and trends in cervical, endometrial, and ovarian cancer in Korean females. Methods Data from the Korea Central Cancer Registry between 1999 and 2010 were analyzed. Age-standardized rates (ASRs) and annual percent changes (APCs) were calculated. Results The absolute incidence rates of the three major gynecologic cancers increased: 6,394 in 1999 to 7,454 in 2010. The ASR for gynecologic cancer was 23.7 per 100,000 in 1999 and decreased to 21.0 in 2010 (APC, -1.1%; 95% confidence interval [CI], -1.53 to -0.70) due to a definitive decrease in the incidence of cervical cancer (APC, -4.3%). Endometrial cancer has been definitively increasing (APC, 6.9% during 1999-2010), especially in females <30 years old (APC, 11.2%) and in females ≥80 years old (APC, 9.5%). The incidence of ovarian cancer is increasing gradually (APC, 1.5%). Conclusion ASRs and APC for gynecologic cancers overall are decreasing due to the decrease in the incidence of cervical cancer. However, the incidence of endometrial and ovarian cancer has been increasing.

Interleukin-10 promoter polymorphisms and cervical cancer risk in Korean women

The aims of this study were to determine whether polymorphisms of the interleukin (IL)-10 promoter might be associated with an increased risk of cervical cancer, and further whether systemic IL-10 concentration might be influenced by the genotypes in Korean women. Peripheral blood samples from patients with invasive cervical cancer (ICC, n=144) and non-cancer controls (NCC, n=179) were used to detect three biallelic IL-10 promoter polymorphisms at -1082, -819, and -592 sites by polymerase chain reaction-restriction fragment length polymorphism assay using MnlI, MaeIII and RsaI, respectively. The IL-10 serum concentration was measured with enzyme-linked immunosorbent assay. We compared the distribution of genotypes in both groups, evaluated the serum IL-10 level according to the genotypes, and analyzed the association of these polymorphisms with the risk of cervical cancer. The genotype at the -1082 site exhibited only the *A homozygote, and only two haplotypes were found in Korean women, one being -1082*A/-819*T/-592*A (ATA) and the other -1082*A/-819*C/-592*C (ACC). No association was found for IL-10 promoter polymorphisms among the ICC patients in comparison with the NCC subjects. The risk of cervical cancer was not increased in either genotype and the IL-10 serum concentration was not influenced by the genotypes in either group. Polymorphisms of the IL-10 promoter do not appear to be associated with cervical cancer risk or systemic IL-10 production in Korean women.

Multiple HPV infection in cervical cancer screened by HPVDNAChip.

This study determined the distribution of high-risk HPV type infection in cervical cancer using newly developed oligonucleotide chips (HPVDNAChips). The study subjects included 80 cases of cervical neoplasia and 746 controls with a normal Pap smear. For HPV genotyping, the commercially available HPVDNAChips was used. The risk of cervical cancer was increased in women with a family history of cervical cancer (adjusted OR=2.3, 95% CI: 0.92-6.17) and in smokers (adjusted OR=3.2, 95% CI: 1.45-7.06). There was also a trend of increased risk with the number of full term pregnancies (P(for trend)<0.001). There were only 7.2% (54 of 746) infected high-risk HPV types in the control, whereas 54.5% (six of 11) and 76.5% (52 of 68) were infected in the CIN and cervical cancer, respectively. Multiple HPV infection was observed in 0.5% (three of 592) of the control group but in 9.1% (seven of 77) of cases. Multivariate analysis revealed that subjects infected with multiple HPV types had a 31.8-fold (95% CI: 7.50-134.75) higher risk of cervical cancer, while the single HPV type had a 19.9-fold increased risk (95% CI: 10.90-36.18) (P(for trend)<0.001). These results show that the detection and typing of HPV infection by HPVDNAChip can be a useful in clinical applications because it provides information on multiple infections and the types of HPV in addition to HPV infection status.

RASSF1A hypermethylation and its inverse correlation with BRAF and/or KRAS mutations in MSI‐associated endometrial carcinoma

Both hypermethylation of the tumor suppressor gene RASSF1A and activating mutations of the KRAS and/or BRAF gene have been reported in a variety of human cancers. To investigate these epigenetic and genetic alterations in endometrial carcinoma (EC), we examined their frequency in 4 uterine EC cell lines and in 75 sporadic primary ECs. Using methylation specific PCR, we found RASSF1A methylation in 25 of 75 (33.3%) ECs. RASSF1A methylation was significantly associated with microsatellite instability (MSI, p < 0.001) and also with hMLH1 methylation (p < 0.001). KRAS mutations were detected in 14 of 75 (18.7%) ECs. BRAF mutations were identified in only 3 of 75 (4.0%) ECs and were not found in ECs with KRAS mutations or RASSF1A methylation. RASSF1A methylation was more frequent in KRAS mutation‐negative ECs than in KRAS mutation‐positive ECs (37.7% vs 14.3%), but this inverse correlation is not statistically significant (p = 0.122). However, we observed that RASSF1A methylation was inversely correlated with KRAS and/or BRAF mutations (p = 0.028) in MSI‐negative ECs, while this inverse correlation disappeared in MSI‐positive ECs. Furthermore, in MSI‐positive ECs, 2 cases of concomitant RASSF1A methylation and KRAS mutation were found. Taken together, these results provide strong evidence that, in EC tumorigenesis, RASSF1A promoter hypermethylation is as important as KRAS mutations in activating the RAS pathway.

Use of serum squamous cell carcinoma antigen for follow-up monitoring of cervical cancer patients who were treated by concurrent chemoradiotherapy

BackgroundTo investigate the significance of monitoring the levels of the serum squamous cell carcinoma antigen (SCC-Ag) for the detection of recurrent disease in patients with cervical cancer treated by concurrent chemoradiotherapy.MethodsThe records of 112 patients with cervical cancer were reviewed. Serum SCC-Ag levels were measured at regular follow-up visits. A SCC-Ag level of 2 ng/mL was considered the upper limit of normal. Biochemical failure was defined as two consecutively increasing SCC-Ag values above normal. Recurrent disease was confirmed by histologic and radiographic studies.ResultsEighteen patients (16%) developed recurrent disease. Sixteen patients had initially elevated SCC-Ag, post-treatment normalization of SCC-Ag, and tumor recurrence. The SCC-Ag difference (ΔSCC-Ag), defined as the difference between the last value after two consecutively increases above normal and the value immediately before the elevation, had good clinical performance in predicting cancer recurrence. The cutoff value of ΔSCC-Ag was 0.95 ng/mL.ConclusionsSCC-Ag is a relatively good method for the detection of disease recurrence in patients with cervical cancer who were treated by concurrent chemoradiotherapy.

Human papillomavirus genotypes and cofactors causing cervical intraepithelial neoplasia and cervical cancer in Korean women.

Objective Infection with human papillomavirus (HPV) is a necessary cause of cervical cancer, but the risk associated with the various viral types and related cofactors have not been adequately assessed in Korean women. This study aimed to investigate the genotype distribution of HPV and cofactors related to cervical carcinogenesis in Korean women. Materials and Methods We conducted a hospital-based case-control study in 215 women with histologically confirmed cervical neoplasia (111 cases of cervical intraepithelial neoplasia [CIN] and 104 cases of invasive cervical cancer [ICC]) and 1214 healthy control women. Polymerase chain reaction–based dot blot assays were used for detection of 16 high-risk HPV types. To clarify the cofactors, we administered questionnaires evaluating smoking, drinking, and sexual and reproductive history from women infected with HPV. Results Human papillomavirus was detected in 86.5% of the women with CIN and 96.2% of the women with ICC compared to 14.6% of the control women. The most common HPV types were, in descending order of frequency, types 16, 58, 18, 33, and 66 for CIN, and types 16, 18, 31, and 33 for ICC. Among the control women, HPV 16, 66, 33, 58, 18, and 31 were the most common types. Smoking and higher number of births (≥3) were associated with CIN (odds ratio [OR], 2.49; 95% confidence interval [CI], 1.21–5.15, and OR, 2.67; 95% CI, 1.36–5.28, respectively). This relationship was also found in the women with ICC (OR, 3.42; 95% CI, 1.59–7.38, and OR, 2.17; 95% CI, 1.08–4.38, respectively) compared to controls. In addition, the circumcision of sexual partner and the sexual habit of condom use were protective factors for ICC (OR, 0.47; 95% CI, 0.24–0.90, and OR, 0.19; 95% CI, 0.06–0.57, respectively). Conclusion Human papillomavirus types 16, 18, 31, 33, and 58 are the major causative genotypes for cervical carcinogenesis in Korean women. Smoking and multiparity seem to be the most significant cofactors.

Role of high risk-human papilloma virus test in the follow-up of patients who underwent conization of the cervix for cervical intraepithelial neoplasia.

OBJECTIVEnTo examine whether the presence of high risk-human papilloma virus (HR-HPV) after conization of the cervix was a risk factor for persistence or recurrence of cervical intraepithelial neoplasia (CIN) and whether HR-HPV test could be a guideline for post-therapy surveillance.nnnMETHODSnThe study retrospectively analyzed data from 243 patients who underwent LLETZ or CKC of the cervix due to CIN.nnnRESULTSnA positive HR-HPV test result which was performed between 3 and 6 months after procedure was a risk factor for persistent or recurrent cytological (p<0.001, odds ratio [OR]=22.51, 95% confidence interval [CI]=9.74-52.02) and pathological (p<0.001, OR=18.28, 95% CI=5.55-60.20) abnormalities.nnnCONCLUSIONnHR-HPV positive patients between 3 and 6 months after procedure should undergo frequent and meticulous post-therapy surveillance, while HR-HPV negative patients do not require such high-level surveillance and could undergo routine surveillance.

Lower extremity edema in patients with early ovarian cancer

BackgroundThe objective of this study was to investigate clinical manifestations of lower extremity edema (LEE) in early ovarian cancer.MethodsPatients with early ovarian cancer who underwent staging surgery between January 2001 and December 2010. Medical records for LEE and/or responses to the Gynecologic Cancer Lymphedema Questionnaire (GCLQ) were evaluated.ResultsPatients had a median age of 46xa0years. Twenty-nine patients (40.8%) had past (13 patients, 44.8%) and/or current patient-reported LEE (16 patients, 55.2%). Symptoms reported on the GCLQ in over 20% of respondents were numbness, firmness/tightness, swelling, heaviness, limited movement of knee, and aching. GCLQ total symptoms score was significantly higher in patients with current LEE. Most of the LEE (25/29, 86.2%) developed within 12xa0months after surgery and LEE lasted more than 6xa0months in approximately two-thirds of the patients (18/29, 62.1%). Only half of the patients (52.1%) indicated knowledge of lymphedema: 86.2% of LEE patients and 28.6% of patients with no LEE.ConclusionsAlthough a significant proportion of patients with ovarian cancer have LEE after surgery, most are not aware of lymphedema until they develop. Education and analyses for LEE and lymphedema are needed in patients with ovarian cancer.

Experiences of pretreatment laparoscopic surgical staging in patients with locally advanced cervical cancer: results of a prospective study

OBJECTIVEnTo prospectively evaluate the feasibility, safety, and survival of laparoscopic surgical staging in patients with locally advanced cervical cancer.nnnMETHODSnFrom Oct 2001 to Jul 2006, a total of 83 consecutive patients were eligible for inclusion and underwent laparoscopic surgical staging.nnnRESULTSnThree patients with intraoperative great vessel injury and 1 patient in whom the colpotomizer was unable to be inserted were excluded. Laparoscopic surgical staging was feasible in 95.2% (79/83). Immediate postoperative complications were noted in 12 (15.2%) patients. Prolonged complications directly related to operative procedures numbered 2 (2.5%), and were trocar site metastases. The mean time from surgery to the start of radiotherapy (RT) or concurrent chemoradiotherapy (CCRT) was 11 (5-35) days. All patients tolerated the treatment well and completed scheduled RT or CCRT without disruption of treatment and additional admission. The rate of modification of the radiation field after surgical staging was 8.9% (7/79). Five-year progression-free survival and overall survival (OS) rates were 79% and 89%, respectively. The OS of patients with microscopic lymph node metastases, which were fully resected, were comparable to those of patients without lymph node metastasis. However, the OS of patients with macroscopic lymph node metastases that were fully resected were poorer compared with those of patients without lymph node metastasis.nnnCONCLUSIONnPretreatment laparoscopic surgical staging is a feasible and safe treatment modality. However the survival benefit of debulking lymph nodes or full lymph node dissection is not clear.

Occult Para-Aortic Lymph Node Metastasis After Negative Positron Emission Tomography/Computed Tomography Scan

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