This study was performed to assess the significance of plasma level and histochemical character of carcinoembryonic antigen(CEA) in early diagnosis and prognosis of ovarian tumor. Plasma level of CEA was measured using EIA method and immunohistochemical tissue staining of CEA was done using biotin-strepto avidin complex immunoperoxidase technique. The percentage of patients with positive CEA level(above 2.5 ng/ml) was 23.1%(6/26) in malignant ovarian tumor and 15.6%(12/77) in benign ovarian tumor. Positive tissue staining of CEA was 42.3%(11/26) in malignant ovarian tumor and 19.5%(15/77) in benign ovarian tumor. In histologic typing, positive tissue staining of CEA was 18.1%(2/11) in serous cystadenocarcinoma, 85.7%(6/7) in mucinous cystadenocarcinoma, 37.5%(3/8) in other malignant ovarian tumors, 7.1%(1/15) in serous cystadenoma, 7.1%(1/14) in mucinous cystadenoma and 27.1%(13/48) in other benign ovarian tumors. Among 5 cases of malignant ovarian tumors with positive CEA level, 3 cases(60%) showed positive tissue staining of CEA, whereas among 21 cases of malignant ovarian tumors with negative CEA level, 8 cases (38.1%) showed positive tissue staining of CEA. However, among 11 cases of benign ovarian tumors with positive CEA level, 4 cases(36.4%) showed positive tissue staining of CEA, whereas among 66 cases of benign ovarian tumors with negative CEA level, 11 cases(16.7%) showed positive tissue staining of CEA. In the 3 year follow-up study of 12 cases with malignant ovarian tumor, among 3 cases with positive tissue staining of CEA, 2 cases(66.7%) survived. In 9 cases with negative tissue staining of CEA, 6 cases(66.7%) survived. In conclusion, these results suggest that the measurement of tumor CEA may be of value in the differential diagnosis of malignant and benign ovarian tumor, especially in diagnosing mucinous cystadenocarcinoma. However, due to the small amount of cases available for study, it was difficult to determine the correlation between the prognosis and tissue CEA staining of ovarian tumors.
Avidin ; Carcinoembryonic Antigen* ; Cystadenocarcinoma, Mucinous ; Cystadenocarcinoma, Serous ; Cystadenoma, Mucinous ; Cystadenoma, Serous ; Diagnosis, Differential ; Early Diagnosis ; Follow-Up Studies ; Humans ; Immunoenzyme Techniques ; Plasma* ; Prognosis

c-erbB-2 oncogene is a gene that encodes a growth factor receptor-like molecule with tyrosine kinase activity and has a structure similar to that of the epidermal growth factor receptor. Overexpression of the c-erbB-2 oncoprotein is detected in human adenocarcinoma of the breast, cervix, and salivary gland, in all of which the association between overexpression of the c-erbB-2 and poor prognosis of the disease has been reported. The role of c-erbB-2 oncoprotein in the tumorigenesis of the human ovary has been poorly understood and remains controversial. In order to explore the relationship between c-erbB-2 oncoprotein status and ovarian carcinoma, tissue from 32 patients, each of whom had invasive ovarian carcinoma prior to treatment, 10 patients with benign cyst and 10 control case who underwent hysterectomy due to gynecological disease at Yonsei University Colloge of Medicine were analyzed. We measured c-erbB-2 oncoprotein with an enzyme-linked immunosorbent assay(ELISA) which was a sandwich type. Patients with invasive ovarian cancer were found to have significantly higher median c-erbB-2 oncoprotein expression than patients with either benign ovarian cyst(P<0.05) or control group(P<0.05), respectively. However there was no significant difference in c-erbB-2 oncoprotein status between benign cyst and control group. verexpression of c-erbB-2 oncoprotein was found in 7 of 32(21.9%) epithelial ovarian cancer. In invasive epithelial cancer, no significant difference in c-erbB-2 oncoprotein levels was noted when stratified according to age, menopausal status, histological cell type, tumor size or surgical stage. Our results were consistent with the concept that c-erbB-2 oncoprotein may play an important role in malignant and tumorigenesis in epithelial ovarian cancer.
Adenocarcinoma ; Breast ; Carcinogenesis ; Cervix Uteri ; Female ; Genes, vif ; Humans ; Hysterectomy ; Oncogenes ; Ovarian Neoplasms ; Ovary ; Prognosis ; Protein-Tyrosine Kinases ; Receptor, Epidermal Growth Factor ; Salivary Glands

Based on the facts that expression of insulin-like growth factors(IGFs), their receptors, and insulin-like growth factor binding proteins(IGFBPs) have been found in many different types of malignancies including human ovarian cancer and their potent mitogenic effects in vitro, a role for IGFs mediated autocrine loop in oncogenesis and growth regulation of human malignancies was suggested. Since ascites support the biological environment for advanced ovarian cancer, it seemed to be resonable to measure the level of growth factors or cytokines in ascites for understanding precise mechanism of those factors in tumor biology. To investigate their roles and to evaluate prognostic significance in ovarian cancer, the IGFs/IGFBPs system were studied in the ascites, not in sera or cystic fluids, from 22 patients with ovarian cancer, who underwent surgical staging and subsequent cis-platinum based systemic chemotherapyery at the Department of Obstetrics and Gnecology, Hanyang University Hospital from Jan. 1989 through Dec. 1994. Ascites from 7 patients with benign disease were used as the control. IGF-I, II, IGFBP-1, and 3 were measured by immunoradiometric assay. The IGF-I level was significantly higher in ascites with ovarian cancer compared with those of benign disease(63.3-/+11.1 vs 17.9-/+6.2ng/ml, p=0.0098), but the level of IGF-II was not significantly different(70.5-/+13.9 vs 70.8-/+31.5 ng/ml, p=0.2827). IGFBP-1 levels were tend to be lower in ascites of patients with ovarian cancer than that of control(25.2-/+9.5 vs 58.6-/+28.2ng/ml, p=0.0637). However, IGFBP-3 levels had no statistically significant difference between two groups(779.7-/+110.6 vs 674.7-/+175.1ng/ml, p=0.8328). Although growth hormone levels were significantly higher in ascites with metastatic ovarian cancer than those of primary epithelial ovarian cancer, the levels of IGF-I, II, IGFBP-1 and 3 in ascites were not significantly different between two groups. IGF-I levels were correlated with the levels of IGFBP-3 in ascites with ovarian cancer(Y=8.83X-2.0, r=0.745, p=0.0000). High level of IGF-I in ascites of patients with ovarian cancer in this study was suggested that IGF-I had an important role on growth regulation of ovarian cancer. As majority of ascites were obtained from advanced and poorly differentiated ovarian cancer patients, IGF-I in ascites seemed to be related with intraperitoneal metastasis. Further large number of study including data from sera or cystic fluid will be needed to elucidate the role of the IGFs and IGFBPs in ascites of patients with ovarian cancer.
Ascites* ; Biology ; Carcinogenesis ; Cisplatin ; Cytokines ; Growth Hormone ; Humans ; Immunoradiometric Assay ; Insulin-Like Growth Factor Binding Protein 1 ; Insulin-Like Growth Factor Binding Protein 3 ; Insulin-Like Growth Factor Binding Proteins* ; Insulin-Like Growth Factor I ; Insulin-Like Growth Factor II ; Intercellular Signaling Peptides and Proteins ; Neoplasm Metastasis ; Obstetrics ; Ovarian Neoplasms* ; Somatomedins*

OBJECTIVE: To evaluate the status of cone margins and severity of cervical neoplasia as predictors of residual lesions in the remaining cervices, and provide guideline for further treatment or close follow-up. METHOD: We performed a 3-year retrospective study and reviewed 95 patients who had undergone cervical conization followed by subsequent hysterectomy. RESULT: The prevalence rates of positive cone margins were 33, 50, 44, 71 and 88% respectively in patients with cervical intraepithelial neoplasia(CIN)II, CIN III, cervical cancer stage Ia1, Ia2 and Ib1. The prevalence rates of positive residual lesions in postcone hy-sterectomy specimens were 0, 31, 19, 29 and 59% respectively in patient with CIN II, CIN III, cervical cancer Ia1, Ia2 and Ib1. Residual lesions were significantly more frequently found in patients with positive cone margins(51%) than in those with negative margins(4.8%). Positive predictive values of margin status for the presence of residual lesions were 0, 56, 36, 40 and 67% respectively. Negative predictive values of margin status for the absence of residual lesions were 100, 94, 94, 100 and 100% respectively. CONCLUSIONS: (1) The prevalence of positive cone margin and residual lesion increased with more severe cervical neoplasia. (2) Positive cone margins had significantly higher risks of residual lesion than negative cone margins. (3) Positive cone margin does not invariably indicate the presence of residual lesion. (4) Negative cone margin does not ensure the absence of residual lesion. Subsequent hysterectomy may be reserved for the patient with CIN III or cervix cancer having positive cone margin or invasive lesion, or the patient who is not reliable for continuous follow-up.
Conization* ; Follow-Up Studies ; Humans ; Hysterectomy ; Prevalence ; Retrospective Studies ; Uterine Cervical Neoplasms

OBJECTIVE: The purpose of this study is to evaluate the histologic correlations and the clinical significance among patients with atypical squamous cells of undetermined significance (ASCUS), atypical glandular cells of undetermined significance(AGUS) and benign endometrial cells identified on cervical Pap smear screening. MATERIALS & METHODS: The computerized files of the Department of Pathology at Samsung Cheil Hospital were searched from 1991 to 1997 to evaluate the annual statistics of cytologic diagnoses including normal/benign, ASCUS, AGUS, low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion(HSIL) and cancer classified by the Bethesda System(TBS). Cytohistologic correlations on follow-up were separately analysed in ASCUS(190 cases), AGUS(268 cases) and benign endometrial cells(169 cases), respectively. Additionally, post-menopausal squamous atypia(83 cases) were also included in this study. TBS terminology was used in both cytologic and histologic diagnoses. RESULTS: During 7-year period (1991-1997), 447,049 cervicovaginal smears were evaluated. The median rate of abnormal cytology was 4.4%, with 2.1% of ASCUS, 2.06% of squamous intraepithelial lesion(SIL), and 0.08% of AGUS. The median ratio of ASCUS versus SIL was 1.24. Specimen adequacy was evaluated on 47,525 cases, of which categories of "satisfactory for evaluation but limited by" and "unsatisfactory for evaluation" were 28.3% and 0.03%, res-pectively. Follow-up of 190 patients with ASCUS cytology showed 30%(57 cases) with SIL on biopsy; 18%(35cases) with LSIL, 11%(21cases) with HSIL, and 1%(1case) with microinvasive squamous cell carcinoma. On histologic examination, 77%(37/48cases) with ASCUS favoring SIL revealed SIL in contrast to 14%(20/142cases) with ASCUS favoring reactive change, which is statistically significant.(Chi-Square test, P<0.0001). Of 83 cases of post-menopausal squamous atypia(PSA), smears with LSIL showed 34.9%(15/43cases) with LSIL on biopsy. 268 patients with AGUS smears had 25%(67cases) with clinically significant cervical or endometrial lesions on histologic examinations. Among 17.9%(48cases) with cervical lesions, squamous abnormalities were 10.5%(28cases); including 1.5%(4cases) with LSIL and 9.0%(24cases) with HSIL. Glandular lesions in cervix were 7.5%(20cases); 3.0%(8cases) of glandular atypia or dysplasia, 1.9%(5cases of adenocarcinoma in situ, 1.1%(3cases) of microinvasive adenocarcinoma and 1.5%(4cases) of adenocarcinoma. Of 7.1%(19cases) of endometrial lesions, 2.2%(6cases) was endometrial hy-perplasia, 4.1%(11cases) endometrial carcinoma, 0.4%(1case) MMMT and 0.4%(1case) metastatic adenocarcinoma from stomach were verified. The pathologies of 169 cases with benign endometrial cells shed in cervicovaginal smears were confirmed to be endometrial polyp(8.3%), endometrial hyperplasia(4.1%) and endometrial carcinoma(5.9%). CONCLUSION: The results of this study indicates that clinicians should communicate with pathologists for proper management of abnormal cytology. Further evaluation and decision of management should be made based on input from pathologists as well as on clinical setting and professional guidelines.
Adenocarcinoma ; Biopsy ; Carcinoma, Squamous Cell ; Cervix Uteri ; Diagnosis ; Endometrial Neoplasms ; Female ; Follow-Up Studies ; Humans ; Mass Screening ; Pathology ; Stomach

To evaluate the efficacy and diagnostic and prognostic significance of two tumor markers (SCCA, CA 125) in patient with squamous cell carcinoma of uterine cervix, the authors studied 215 patients with squamous cell carcinoma in situ and invasive carcinoma from September 1993 to November 1996. Both tumor markers were measured coincidently in 215 patients preopera-tively and in 70 cases of benign gynecologic disease for control group. Serum SCCA level of 2.5 ng/ml and CA 125 level of 35.0 U/ml were determined as cut-off levels. The results were as follows: 1. The pretreatment positive rate of SCCA in patient group were 35.8 %(77/215) and 5.7 %(4/70) in control group. 2. The mean values and positive rates of SCCA according to clinical stage were 1.44+/-3.59 ng/ml(8.7 %) for stage 0, 3.81+/-10.22 ng/ml(23 %) for stage I, 8.54+/-15.23 ng/ml(51.3 %) for stage II, 35.54+/-38.34 ng/ml(70.0 %) for stage III, 22.49+/-36.06 ng/ml(75.0 %) for stage IV, 40.33+/-58.66 ng/ml(66.7 %) for recurrent cancer, respectively. The mean SCCA value and positive rate were significantly increased stepwise by clinical stage from stage I to stage III (P<0.05). 3. The pretreatment positive rate of CA 125 in patient group were 21.9 %(47/215) and 17.1 %(12/70) in contrl group. 4. In pre-invasive and invasive groups, the mean value and positive rate of SCCA were 1.44+/-3.59 ng/ml(8.7 %), 9.05+/-25.26 ng/ml(43.2 %), respectively, and it was statistically significant between two groups (P<0.05). The mean values and positive rate of CA 125 were 24.36+/-16.14 U/ml(10.9 %), 35.15+/-59.52 U/ml(24.9 %), respectively, it was not statistically significant (P>0.05). 5. The result of preoperative serum levels of SCCA can be characterized by 35.8 % sensitivity, 94.3 % specificity, 95.1 % positive predictive value, 32.4 % negative predictive value, 49.5 % diagnostic efficiency, and with 21.9 %, 82.8 %, 79.7 %, 25.7 %, 36.8 % respectively for CA 125. Between these two tumor markers, the result of SCCA was more valuable than the other in sensitivity, positive predictive value, negative predictive value and diagnostic efficiency. The results indicate that measurement of SCCA and/or CA 125, have little efficacy in the early detection of squamous cell carcinoma considering it's low rate of positivity in preinvasive and early stage of invasive squamous cell carcinoma. However, in patients with advanced stage invasive carcinoma, measurement of serum SCCA is useful in prediction of prognosis and in early detection of recurrence, and concomitant measurements of SCCA and CA 125 may be more useful in determining prognosis, therapeutic response, and early detection of recurrence than measurement of SCCA alone.
Carcinoma, Squamous Cell* ; Cervix Uteri* ; Female ; Genital Diseases, Female ; Humans ; Prognosis ; Recurrence ; Sensitivity and Specificity ; Biomarkers, Tumor*

HPV E2 protein is known to act as a negative regulator of transcription and the disruption of E2 open reading frame by HPV integration can release suppression of E6 and E7 mRNA expression, resulting in uncontrolled cellular growth and malignant transformation by inactivating tumor suppressor gene products (p53, pRb). YY1 mutation of HPV URR has been suggested as one of indicator that explains development of cervical neoplasia by episomal type of HPV. To extend this hypothesis, we examined whether mutation(s) in specific sites of HPV URR is functionally related to the invasiveness of cervical neoplasia and the physical status of HPV DNA. The URR sequences were obtained by PCR amplification of HPV-16 genome from CIN and invasive cancer patients, cloned into pUC18 for sequencing, and into pBLCAT8+ for functional CAT assay. Our previous data classified HPV-infected patients into three groups: 3 cancer cases carrying episomal HPV DNA; 12 cancer cases carrying integrated HPV DNA; 12 CIN cases carrying episomal HPV DNA. The specific variants in HPV-16 URR were found in Korean women: GA transition at nt 7520 (100%, 27/27), AC transition at nt 7729 (70%; 19/27), and GA transition at nt 7841 (78%; 21/27). Selective mutations were observed at the YY1-binding sites of HPV-16 URR in the 3 patients with invasive cervical cancer, who having the episomal forms of HPV-16 DNA: AC transition at nt 7484 and GA transition at nt 7488 (YY1-binding site 2; from 7481 to 7489). Additionally, CT transition at nt 7785 (YY1-binding site 3; from 7781 to 7790) was found from 2 of 3 patients. No YY1 site mutations were detected in the 12 CIN patients and in the HPV-integrated invasive cancer patients. To determine whether these mutations have effect on the expression of HPV E6/E7 genes driven by URR, the transient transfection assay was employed using URR-CAT reporter plasmid. The relative activities of three URR mutants from episomal HPV-16 DNA of cervical cancers were 2- to 4-fold higher than that of HPV-16 URR prototype. In contrast, the URRs from integrated HPV-16 DNA in cervical cancer and from episomal HPV-16 DNA in CIN, where no mutation of the YY1-binding site was detected, showed similar levels of promoter activity to that of URR prototype.Our results support the hypothesis that the mutation at YY1 binding site is functionally related to the development of cervical neoplasia caused by episomal HPV-16 DNA in Korean cervical cancer patient. Thus, mutation in YY1 site of episomal HPV-16 URR may play a role of HPV integration in the progression of cervical cancer.
Animals ; Binding Sites ; Cats ; Clone Cells ; DNA* ; Female ; Genes, Tumor Suppressor ; Genome ; Human papillomavirus 16* ; Humans ; Open Reading Frames ; Plasmids ; Polymerase Chain Reaction ; RNA, Messenger ; Transfection ; Uterine Cervical Neoplasms

The cell cycle is the set of events that is responsible for the duplication of the cells. Recent studies indicate that cell cycle regulatory proteins, mainly the cyclins and cyclin-related genes, can be critical targets during oncogenesis. The genes and gene products normally control specific events in the cell cycles, particularly during the late G1 and early S phase and G2/M phase. A large body of date implicates cyclins in oncogenesis. The first evidence came from human cyclin A in oncogenesis. Cyclin A is expressed from the late G1 phase through the M-phase of the cell cycle. Cyclin A is known as positive regulator of cell cycle and participates in the tumorigenesis. Overexpression of cyclin A has been reported in several cancers. Ki-67 is a nuclear protein expressed during the cell cycle except in Go. The labeling index of Ki-67 in the tumor cell nuclei has been used as a good prognostic factor. In this study, we compared labeling index of cyclin A and Ki-67 to assess the feasibility between them with 30 cases of cervical intraepithelial neoplasia(CIN) and 20 cases of invasive squamous cell carcinoma(SCC)by immunohistochemistry. The results were as follow; 1. Cyclin A expressed in normal parabasal cells and their labeling index was 0.8+/-0.4%, while in CIN and invasive SCC 65.5+/-9.4% and 86.5+/-12.3% respectively. Ki-67 expressed in normal parabasal cells as 1.3+/-0.7% while in CIN and invasive SCC as 77.8+/-12.9% and 92.2+/-17.6% respectively. 2. In CIN, the expression of cyclin A increased according to the grades of the CIN as 32.5+/-5.7%, 75.8+/-9.0%, and 83.2+/-13.4% in CIN I, II and III respectively. The expression of the Ki-67 also increased according to the grades of the CIN as 51.8+/-9.8%, 87.9+/-11.3%, and 93.6+/-17.5% respectively in CIN I, II and III. 3. There was no differences of cyclin A and Ki-67 expressions according to the histologic types of invasive SCC. Above results suggests that the cyclin A labeling index could be used as a marker of tumor progression in the uterine cervical carcinoma as Ki-67.
Carcinogenesis ; Cell Cycle ; Cell Cycle Proteins ; Cell Nucleus ; Cyclin A* ; Cyclins* ; G1 Phase ; Humans ; Immunohistochemistry ; Nuclear Proteins ; S Phase

BACKGROUNDS: Human papillomavirus (HPV) infection is known as the major causative phenomenon in the development of cervical cancer. E6 and E7 proteins of oncogenic HPV types can play critical roles in immortalization and malignant transformation of cervical epithelial cells. From the previous epidemiologic data, long term use of oral contraceptives may be one of the risk factor for cervical cancer. PURPOSE: Investigation of estrogenic and anti-estrogenic effects on the proliferation of cervical cancer cells and gene expression of HPV under the regulation of HPV upstream regulatory region (URR) would help to explain the role of estradiol in HPV-associated pathogenesis of cervical cancer. METHODS: Cervical cancer cells (HeLa, CaSki and C33A) were cultured in vitro in the presence of 17 beta-estradiol or tamoxifen and the numbers of cells were directly counted to observe the growth stimulatory or suppressive effect of the treatment. The correlation between the growth regulatory effect and HPV E6/E7 gene expression was determined by reverse transcription-polymerase chain reaction (RT-PCR). The estrogenic effect on the promoter activity of HPV URR was further confirmed by transient co-transfection assays, which were conducted in C33A cells using the HPV-18 URR-CAT reporter plasmid. Supplemental effect of estrogen receptor on the URR promoter activity was also evaluated. To analyze the growth suppressive function at the higher concentration of estradiol or tamoxifen in HeLa cells, DNA fragmentation assay was performed. RESULTS: The proliferation of HeLa and CaSki cells was stimulated by estradiol at the concentration of physiological level (< or =1 X 10-6M), reaching maximal growth at 0.5 X 10-6M. At concentration of 0.1 X 10-6M, tamoxifen also stimulated the proliferation of HeLa and CaSki cells. In contrast to HPV-positive cervical cells, C33A cells were not influenced to cell proliferation by addition of estradiol at the physiological level, indicating that HPV might play role in growth stimulatory effect of estrogen or tamoxifen. Interestingly, the proliferation of HeLa cells was totally suppressed by estradiol and tamoxifen at the higher concentration (5 and 10 X 10-6M), whereas those of CaSki and C33A cellswere not responded and little suppressed at the concentration, respectively. The levels of HPV-18 E6 and E7 mRNA were significantly increased after treatment of 0.5 X 10-6M estradiol as determined by RT-PCR. Furthermore, transient transfection experiments using the URR-CAT reporter plasmid indicated that the increased expression of HPV E6/E7 genes was related with the growth stimulatory effect of estradiol and tamoxifen. In addition, co-transfection of estrogen receptor (ER) leads to an over 4-fold increase in CAT activity after treatment of estradiol or tamoxifen with 0.5 X 10-6M. When estradiol or tamoxifen was treated at the concentration over 5 X 10-6M for 96 hr, a typical DNA ladder, a indicative of apoptosis, was observed in HeLa cells. However, DNA ladder was not detected in C33A cells of which growth was some suppressed under same concentration of estradiol. CONCLUSION: At the physiological levels, estradiol stimulated the growth of HPV-positive cervical cancer cells and tamoxifen also did at the concentration of 0.1 X 10-6M. The increased expression of HPV E6/E7 at the physiologic levels appeared to be related with the growth stimulation of HPV-positive cervical cancer cells. Growth suppression observed at the higher concentration (5 and 10 X 10-6M) might be a indicative of apoptosis shown by DNA fragmentation assay in HeLa cells. Taken together, these data suggested that the concentration of estradiol (< or =1 X 10-6M) could be a risk-factor in HPV-mediated cerivcal carcinogenesis.
Animals ; Apoptosis ; Carcinogenesis ; Cats ; Cell Proliferation ; Contraceptives, Oral ; DNA ; DNA Fragmentation ; Epithelial Cells ; Estradiol ; Estrogens* ; Gene Expression ; HeLa Cells ; Human papillomavirus 18 ; Humans ; Plasmids ; Regulatory Sequences, Nucleic Acid ; Risk Factors ; RNA, Messenger ; Tamoxifen ; Transfection ; Uterine Cervical Neoplasms*

PURPOSE: To set up more simplified detection method for human papillomavirus (HPV) sequence polymorphism which could be used for the study of HPV-related pathogenesis, route of infection, and many other epidemiologic studies. MATERIALS AND METHODS: One hundred and thirteen cases of uterine cervical tissues containing HPV 16 DNA confirmed by polymerase chain reaction (PCR) from Korean women were subjected to investigate the URR gene mutations. PCR-amplified products were sequenced by the fluorescent dideoxy termination method and opposite strand sequencing was performed as required. The results obtained from sequencing were analysed to find the most hypervariable segment which contains the greatest number of variants and subjected to PCR-single strand conformation polymorphism (SSCP) analysis. RESULTS: Among the length of nucleotide position (np) from 7175 to 24, we found 60 sites (60/815=7.36%) of base substitutions. Segment from np 7743 to 24 was the most hypervariable and contain 20 kinds of variants. In this segment, C-to-T mutation at position 24, G-to-A at 7842, and T-to-C at 7781 were more frequently found than other sites. By comparing sequencing results with PCR-SSCP, we found 15 patterns distinguishable each other. All of the mobility shift occurred in the PCR-SSCP pattern could be accounted for by the base substitutions and nearly all of the DNA sequencing results observed were reflected as alterations in the PCR-SSCP patterns. CONCLUSIONS: We have assigned the hypervariable segment in one portion of URR which could be used as PCR-SSCP analysis. Identification of HPV polymorphism by PCR-SSCP is potentially useful for elucidating a number of epidemiologic questions such as the pathway of viral spread and so on.
DNA ; Female ; Human papillomavirus 16 ; Humans* ; Molecular Epidemiology ; Polymerase Chain Reaction ; Sequence Analysis, DNA