Mammography screening: views from women and primary care physicians in Crete.

BACKGROUND: Breast cancer is the most commonly diagnosed cancer among women and a leading cause of death from cancer in women in Europe. Although breast cancer incidence is on the rise worldwide, breast cancer mortality over the past 25 years has been stable or decreasing in some countries and a fall in breast cancer mortality rates in most European countries in the 1990s was reported by several studies, in contrast, in Greece have not reported these favourable trends. In Greece, the age-standardised incidence and mortality rate for breast cancer per 100.000 in 2006 was 81,8 and 21,7 and although it is lower than most other countries in Europe, the fall in breast cancer mortality that observed has not been as great as in other European countries. There is no national strategy for screening in this country. This study reports on the use of mammography among middle-aged women in rural Crete and investigates barriers to mammography screening encountered by women and their primary care physicians. DESIGN: Semi-structured individual interviews. SETTING AND PARTICIPANTS: Thirty women between 45-65 years of age, with a mean age of 54,6 years, and standard deviation 6,8 from rural areas of Crete and 28 qualified primary care physicians, with a mean age of 44,7 years and standard deviation 7,0 serving this rural population. MAIN OUTCOME MEASURE: Qualitative thematic analysis. RESULTS: Most women identified several reasons for not using mammography. These included poor knowledge of the benefits and indications for mammography screening, fear of pain during the procedure, fear of a serious diagnosis, embarrassment, stress while anticipating the results, cost and lack of physician recommendation. Physicians identified difficulties in scheduling an appointment as one reason women did not use mammography and both women and physicians identified distance from the screening site, transportation problems and the absence of symptoms as reasons for non-use. CONCLUSION: Women are inhibited from participating in mammography screening in rural Crete. The provision of more accessible screening services may improve this. However physician recommendation is important in overcoming women's inhibitions. Primary care physicians serving rural areas need to be aware of barriers preventing women from attending mammography screening and provide women with information and advice in a sensitive way so women can make informed decisions regarding breast cancer screening.

Human placental growth hormone is increased in maternal serum in pregnancies affected by Down syndrome.

OBJECTIVE: To evaluate the relationship between maternal serum levels of human placental growth hormone (hPGH) and fetal Down syndrome at gestational midtrimester. METHODS: We retrospectively analyzed samples of serum from 21 women with Down syndrome pregnancies detected at gestational midtrimester. The samples were obtained at 16-23 weeks' gestation during amniocentesis for fetal karyotyping. Sixty-two serum samples were used as controls, which were obtained at 16-23 weeks' gestation from women with singleton, uncomplicated pregnancies, who gave birth to healthy neonates with a birth weight appropriate for gestational age. The hPGH levels were measured by a solid-phase immunoradiometric assay using 2 different epitopes. RESULTS: The median hPGH values in the serum of the Down-syndrome-affected pregnancies were significantly higher (p < 0.05) than those of the normal pregnancies at 16-23 weeks' gestation: the median value in the serum was 9.4 ng/ml (5th to 95th percentiles = 1.49-39.03) versus 4.7 ng/ml (0.53-7.88). CONCLUSION: The hPGH levels in maternal serum were found to be higher at 16-23 weeks' gestation in pregnancies affected by fetal Down syndrome. Further investigation is needed to examine if maternal serum hPGH could be used as an additional marker in prenatal screening of Down syndrome at gestational midtrimester.

Relationship between BMD, dental panoramic radiographic findings and biochemical markers of bone turnover in diagnosis of osteoporosis.

OBJECTIVE: Mandibular indices, measured on panoramic radiographs, may be useful screening implements for low skeletal bone mass density (BMD). Recent studies suggest that radiographic examination of mandible may constitute an effective process for the early diagnosis of osteoporosis. Biochemical markers of bone turnover may be of value for prediction of individual bone loss and they may help in predicting risk of fracture in elderly women. In contrast to the vast information available on dental radiographic findings and BMD only scarce data exist on the relationship between panoramic mandibular indices and biochemical markers. The aim of this study was to examine the diagnostic performance of dental panoramic radiography and biochemical markers of bone turnover in relation to BMD at the spine in a group of postmenopausal women. SUBJECTS AND METHODS: An assessment of the number of lost teeth, mandibular cortical width (MCW) at the mental region and morphologic classification of mandibular inferior cortex (MIC grade) was performed on dental panoramic radiographs in a group of 141 postmenopausal women 38-81 years of age. BMD at the lumbar spine was measured by dual energy X-ray absorptiometry. BMD values were categorized as normal (T-score greater than 1.0), and as indicative of osteopenia (T-score -1.0 to -2.5) or osteoporosis (T-score less than -2.5) according to the World Health Organization classification. Serum bone alkaline phosphatase (BAP) was measured with an enzyme immunoassay. Cross-linked N-telopeptides of type I collagen (NTx) corrected for creatinine secretion, was measured with a competitive-inhibition enzyme-linked immunosorbent assay ELISA. RESULTS: In our study, a decrease in MCW by 1mm increases the likelihood of osteopenia or osteoporosis to 47% (p-value<0.05), having taken into consideration the effect of the years elapsed since menopause. The increase of alkaline phosphatase (ALP) per unit increase the likelihood of osteopenia or osteoporosis to 14% (p-value<0.05), having checked the effect of the years since menopause. A decrease in MCW by 1mm increases the likelihood of moderately or severely eroded cortex to 97% (p-value<0.001). The increase in ALP per 1 unit increases the likelihood of moderate or severe erosion per 10% (p-value<0.05), taking into account the years since menopause. CONCLUSIONS: Our results suggest that dentists have sufficient clinical and radiographic information that enables them to play a significant role in early diagnosis of osteoporosis in postmenopausal women. Panoramic radiographs and biochemical markers of bone turnover may be of value for prediction of individual bone loss and they may help in predicting risk of fracture in elderly women.

Mandibular radiomorphometric measurements as indicators of possible osteoporosis in postmenopausal women.

OBJECTIVE: The use of mandibular anatomic indicators on panoramic radiographs, i.e. the number of lost teeth, mandibular cortical width at the mental region (MCW), panoramic mandibular index (PMI), alveolar crest resorption degree (M/M ratio) and morphologic classification of the mandibular inferior cortex (MIC grade) can be useful in the evaluation of bone resorption in different age groups of women to determine the presence of osteoporosis. The purpose of this study was to assess the validity of mandibular radiomorphometric measurements and to determine the frequency of tooth loss in postmenopausal women. SUBJECTS AND METHODS: An assessment of the number of lost teeth, MCW, PMI, M/M ratio and MIC grade was performed on dental panoramic radiographs in a group of 133 postmenopausal women 38-80 years-of-age. BMD at the lumbar spine was measured by dual energy X-ray absorptiometry. BMD values were categorized as normal (T-score greater than 1.0), and as indicative of osteopenia (T-score -1.0 to -2.5) or osteoporosis (T-score less than -2.5) according to the World Health Organization classification. RESULTS: In our study when the T-score at the lumbar spine is decreased, the age of menopause is increased, and the MCW is decreased to a point of statistical significance. A decrease in MCW by 1mm increases the likelihood of osteopenia or osteoporosis to 43%, having taken into consideration the effect of the years elapsed since menopause. It was also shown that age, years since menopause, MCW value, and the number of teeth lost have a statistically important effect on the incidence of moderate or severe cortical erosion. Moreover, when the MCI is C2 or C3 (mild or severe erosions) the age is increased, the years since menopause are increased and the MCW is decreased to a point of statistical significance. As far as tooth loss is concerned, an increase by 1 unit in the number of teeth lost, increase the likelihood of moderate or severe erosion to 6%, having taken into account the years elapsed since menopause. Our study also demonstrated that postmenopausal women tend to lose their teeth at an age older than 50 years. They usually lose the 1st and 2nd mandibular molars and the 1st and 2nd maxillary premolars. Loss of front teeth and canines occurs at an age older than 60 years (except for the lateral maxillary incisors). At a younger age they tend to lose the 2nd maxillary premolars more frequently than their mandibular counterparts. CONCLUSIONS: In conclusion, panoramic radiographs constitute an integral part of almost every routine dental evaluation and can be useful for the early diagnosis of osteoporosis in postmenopausal women. Dentists have sufficient clinical and radiographic information that enables them to play a significant role in patient screening for osteoporosis.

Endometriosis mimicking advanced ovarian cancer.

OBJECTIVE: To report a case of endometriosis associated with massive ascites, pleural effusion, and extremely elevated Ca-125. DESIGN: Case report. SETTING: University hospital. PATIENT(S): A 46-year-old, white nulligravida with bilateral adnexal masses, Ca-125 of 3,504 U/mL, abdominal pain, ascites, and a pleural effusion. INTERVENTION(S): Chemotherapy followed by exploratory laparotomy for suspected ovarian cancer. MAIN OUTCOME MEASURE(S): Surgical findings and histopathology. RESULT(S): Intraoperative examination and histology ruled out malignancy but found stage IV endometriosis. CONCLUSION(S): In rare instances advanced endometriosis may be associated with ascites, pleural effusions, and large pelvic masses. For this reason endometriosis should be included in the differential diagnosis of reproductive-age women presenting with apparent ovarian malignancy.

Prenatal diagnosis of a fetal chest wall cystic lymphangioma using ultrasonography and MRI: a case report with literature review.

A case of fetal chest wall cystic lymphangioma diagnosed prenatally at 28 weeks' gestation is reported. Ultrasound examination showed a multilocular, large cystic mass (10 x 22 x 29 mm) on the left side of the fetus in the area of the lower chest and upper abdomen, without color flow imaging. Magnetic resonance imaging was used to evaluate the extent and the tissue characteristics of the lesion. Two months after birth the lymphangioma was surgically removed, following an infection and a rapid increase in size. The case is discussed, and a short review of the literature is reported.

High-dose misoprostol used in outpatient management of first trimester spontaneous abortion.

AIM: The aim of this study was to evaluate the efficacy and tolerance of a high dose of vaginal misoprostol for outpatient medical management of missed abortion. METHODS: Three doses of 400 mug misoprostol were administered intravaginally every 4 h daily, for a maximum period of 3 days, to 108 women with uneventful first trimester pregnancy failure. RESULTS: A total of 98 women (90.7%) were managed successfully, with 74 (68.5%) of them within the first 24 h. The mean dose of misoprostol administered was 1,113.0 microg (range 400-3,600 microg), and the mean time required was 19.5 h (range 7-65 h). Only 6 out of 108 women (9.3%) required surgical intervention as the result of retained products of conception. The side effect profile was minimal. CONCLUSION: This protocol of 400 mug intravaginally misoprostol every 4 h as three daily doses for a maximum of 3 days, may offer an efficacious and safe alternative to the outpatient management of first-trimester missed abortion.

VEGF, FGF2, TGFB1 and TGFBR1 mRNA expression levels correlate with the malignant transformation of the uterine cervix.

Angiogenesis is a complex procedure induced by the secretion of numerous growth factors from endothelial cells. Vascular endothelial growth factor (VEGF), basic fibroblastic growth factor (FGF2), transforming growth factor-beta1, 2, 3 (TGFB1, 2, 3), and transforming growth factor-beta receptors (TGFBR1, 2, 3) mRNA expression pattern was evaluated in tissue samples with cervical intraepithelial neoplasia (CIN) and cervical cancer, compared to that of normal cervical tissues, and correlated to the clinical stage of the disease. Transcript levels of the above genes were assessed by RT-PCR analysis in a total of 44 cervical specimens. VEGF, TGFB1, TGFBR1, and FGF2 transcript levels were significantly different in the normal, CIN and cancer specimen groups (P=0.015, 0.001, 0.008, and 0.029, respectively). Higher TGFBR1 mRNA levels were observed in parallel with increased severity of the lesion, whereas FGF2 exhibited lower transcript levels. A highly significant increase of VEGF mRNA expression was found upon cervical neoplastic transformation (P<0.0001). High-grade squamous intraepithelial lesions exhibited higher VEGF mRNA levels than low-grade lesions (P=0.039). TGFBR1 and TGFBR3 receptors demonstrated significant co-expressions with TGFB2 (P<0.0001), and TGFB1 (P=0.005 and 0.002, respectively) in normal cervical specimens. However, a disruption of co-expression patterns was observed in the groups of CIN and cancer cases, compared to normal tissues. Our findings show that VEGF, FGF2, TGFB1 and TGFBR1 mRNA expression levels correlate with the malignant transformation of the uterine cervix. The involvement of the examined markers in cervical carcinogenesis is furthermore supported by the observed disruption of their mRNA co-expression patterns.

High concentrations of the CA-125, CA 19-9 and CA 15-3 in the peritoneal fluid between patients with and without endometriosis.

OBJECTIVE: In the present study we compared the levels of CA-125, CA 19-9, and CA 15-3 in the peritoneal fluid (PF) of patients with and without endometriosis, then assessed the possibility of a correlation among these tumor markers. STUDY DESIGN: Our study was a controlled clinical study of patients undergoing laparoscopy for infertility or other benign gynecology conditions. Peritoneal fluid samples were collected from 65 women with endometriosis and 43 women without pelvic disease. Levels of CA-125, CA 19-9 and CA 15-3 in the peritoneal fluid were determined by immunoradiometric assay. RESULTS: The concentration of CA-125 in PF from patients with endometriosis was significantly higher than that in the control group (p<0.001); for CA 19-9 and CA 15-3, PF concentrations were not statistically different between these two groups. Women with endometriosis had significantly higher levels of CA-125 in proliferative and secretory phases than the control group (p<0.001 and p<0.002 respectively); furthermore, in patients with endometriosis the CA 19-9 levels were significantly lower in secretory phase than the proliferative (p<0.004). The levels of CA-125 were significantly lower in women with tubal ligation, in comparison with infertility or pelvic pain in the control group (p<0.001). No significant difference was seen in women with infertility or pelvic pain in endometriosis group and the levels of CA-125, CA 19-9, and CA 15-3. We did not find any correlation between the stages of endometriosis and the concentration of CA-125, CA 19-9 and CA 15-3. A significant correlation between the CA 19-9 levels and CA 15-3 in patients with endometriosis was found (r=0.72, p=0.001). CONCLUSIONS: We found high concentrations of CA-125, CA 19-9, and CA 15-3 in the peritoneal fluid of women with and without endometriosis in the Yale series. However, the levels only of CA-125 were higher in women with endometriosis, but without diagnostic value. The role of simultaneously high concentrations of CA 19-9 and CA 15-3 in women with endometriosis needs to be explored further.

Chemoprophylactic and bactericidal efficacy of 80 mg gentamicin in a single and once-daily dosing.

OBJECTIVE: The objective was to examine the biodistribution, the chemoprophylactic, and the bactericide efficacy of 80-mg gentamicin single or once-daily dosing. STUDY DESIGN: Ninety-six patients who had had cesarean section or gynecological surgery received 80 mg gentamicin for chemoprophylaxis. A second group of 92 patients with Gram-negative infection received once-daily 80-mg gentamicin intramuscularly, combined with cefoxitin or ceforanide, for 5 days. Gentamicin serum and tissue concentration was determined 1 h after the first administration. RESULTS: The chemoprophylactic efficacy of gentamicin was 93.7%. The treatment efficacy was high in patients with chorioamnionitis and endometritis (92.9%), moderate in those with wound infection (69.5%), and less effective in those with septicemia (55.6%). Twenty-six percent of patients continued with antibiotics for infection control. The mean serum level was 4.48+/-0.49 and 5.56+/-0.66 microg/ml in obstetrical and gynecological patients respectively (p>0.05). Serum levels >4 microg/ml were achieved in 91% of patients. CONCLUSIONS: A single dose of 80 mg gentamicin offers chemoprophylaxis and achieves therapeutic serum-concentrations 1 h after administration. The 5-day combination of once-daily 80 mg gentamicin with a second-generation cephalosporin is effective in patients with chorioamnionitis and endometritis, but only moderately effective in those with wound infections and septicemia.

A clinical study of optical biopsy of the uterine cervix using a multispectral imaging system.

OBJECTIVE: To present the clinical application of the multispectral imaging colposcopic system (MIS colposcopy). METHODS: MIS colposcopy was performed on 123 enrolled women. After a 3% acetic acid application, sequential images were captured, analyzed, and stored automatically. Directed biopsies were taken from distinct marked acetic acid-responsive tissue areas indicated on the monitor, while a real-time assessment of the curves of intensity of the backscattered light (IBSL) vs. time was performed. Blind biopsies were taken from non-acetowhitening areas. Histological findings were correlated with MIS colposcopy results and compared with conventional colposcopy and Pap test results. RESULTS: Acetic acid-tissue interaction resulted in temporal and spatial alterations to the light scattering properties of the abnormal tissue that was analyzed. The shape of IBSL curve and the "relaxation time" (the time it takes for IBSL to decay to 1/e of its peak value) changed in accordance with the underlying lesion. More severe CIN lesions lead to higher maximum IBSL; longer durations of acetowhitening lead to increasingly delayed exponential decay of IBSL curve. To compare with histological examination, MIS colposcopy had a 1.7% false-diagnostic rate, while PAP test and conventional colposcopy had 24.4% and 22% false-diagnostic rates, respectively. A triple exponential function created a "pseudocolor" image that comprised the grade map of the lesion, and this is frequently representative of the duration/degree of the induced alterations. CONCLUSION: Improved diagnostic information can be gained by recording the optical information in a narrow spectral range with high spatial resolution. MIS colposcopy can be used in the diagnosis of uterine cervix pathological conditions and in the differentiation between CIN lesions.

Prenatal diagnosis of trisomy 2 mosaicism: a case report.

We report a case of trisomy 2 mosaicism detected upon amniocentesis in a woman with advanced maternal age. A mos 47,XY,+2(4)/46,XY(21) karyotype was revealed using standard GTG banding. There were no pathological sonographic findings and the fetal size was normal for gestational age at 16th week. The use of serial high-resolution ultrasound examination of the fetus to detect major abnormalities was offered as an option to the parents who, however, decided for termination of the pregnancy. Fetal autopsy did not reveal any malformations. Trisomy 2 mosaicism is associated with variable phenotypic abnormalities without a specific pattern, intrauterine growth restriction, fetal demise or stillbirth. The rarity of trisomy-2 mosaicism in prenatal diagnosis, as well as the increased risk of an abnormal outcome makes the diagnostic approach and genetic counseling difficult.

Transcriptional activation of H- and N-ras oncogenes in human cervical cancer.

OBJECTIVE: Overexpression of p21 protein has been detected in human cervical cancer. However, to date, there are no data on the differential activation of the three ras genes at the transcriptional level in cervical lesions. The purpose of this study was to evaluate the quantitative and qualitative changes of expression of the ras family genes in the development of human cervical cancer. METHODS: The expression of ras mRNA levels in 35 human cervical specimens [11 normal cervix, 15 cervical intraepithelial neoplasia (CIN), 9 cervical cancer] was examined using the RT-PCR technique. In addition, we studied the incidence of point mutations in codon 12 of each ras gene using RFLP analysis and human papilloma virus (HPV) status. RESULTS: The transcript levels for H-ras and N-ras were significantly higher in cancer cases compared to normal cervical tissues (P=0.0002 and P=0.001, respectively) and CIN lesions (P<0.0001 and P=0.002, respectively). The transcript levels for K-ras were similar in normal cervical tissue, CIN and cervical cancer. A strong positive correlation was found between H- and N-ras expression (P=0.001) and no correlation between H- and K- or N- and K-ras expression. Point mutations were detected only in three samples, located in codon 12 of K-ras gene. No relationship was found between expression levels of each ras gene and the presence of HPV. CONCLUSION: Our findings indicate the expression pattern of the three ras genes in cervical tissue and the involvement of H- and N-ras up-regulation in the pathogenesis of cervical cancer independent of HPV infection.

CYP1A1, CYP19, and GSTM1 polymorphisms increase the risk of endometriosis.

OBJECTIVE: To investigate the possibility of genetic contribution of CYP1A1, CYP19, GSTM1, and GSTT1 polymorphisms to endometriosis. DESIGN: Genetic polymorphism analysis. SETTING: Case-control study. PATIENT(S): A group of 275 women with sporadic endometriosis was compared with a group of 346 fertile, endometriosis-free women. INTERVENTION(S): Surgical, laparoscopic, and histological examination. MAIN OUTCOME MEASURE(S): Blood specimens were obtained from endometriosis cases and controls. Polymerase chain reaction-based assays were performed for the determination of individual's genotype. RESULT(S): The CYP19 VNTR, located in intron 4 (TTTA)(10) allele increases the risk for endometriosis development (odds ratio [OR], 4.99; 95% confidence interval [95% CI], 1.351 to 18.436). The combined genotype CYP1A1 wt/m1 or m1/m1 and GSTM1 null deletion adds to this risk (OR, 1.95; 95% CI, 1.266 to 2.995 and OR, 2.23; 95% CI, 0.631 to 7.906, respectively). In contrast, the CYP1A1 wt/wt genotype exhibits a protective effect, with a 38% reduction in the odds for endometriosis development (OR, 0.62; 95% CI, 0.440 to 0.883). CONCLUSION(S): Our data suggest that CYP19 VNTR (TTTA)(10) allele as well as the combined genotype CYP1A1 m1 polymorphism and GSTM1 null deletion associate with the endometriosis phenotype, whereas the GSTT1 null deletion does not.

Diagnostic role of inhibin B in resistant ovary syndrome associated with secondary amenorrhea.

To report two rare cases of gonadotropin-resistant ovary syndrome associated with secondary amenorrhea and normal levels of inhibin B. Case report. Two university teaching hospitals. Two women presenting with secondary amenorrhea and infertility. The control group for the inhibin B levels consisted of 30 cycling women of reproductive age. Medical history, physical examination, laboratory data, histologic findings, and IVF results. Diagnosis and treatment of resistant ovary syndrome. Case 1 was a 25-year-old woman with secondary amenorrhea and primary infertility. She had high serum levels of FSH and LH, low E(2) levels, and normal inhibin B levels (62 pg/mL). Karyotype was 46,XX, and ovarian biopsy showed primordial follicles with oocytes. Administration of GnRH analogue with hMG for 15 days did not affect E(2) levels. She had a successful pregnancy with IVF using donor oocytes. Case 2 was a 24-year-old woman with secondary amenorrhea. She had elevated serum levels of FSH and LH, low E(2) levels, and normal inhibin B levels (57 pg/mL). Karyotype was 46,XX and ovarian biopsy showed primordial follicles. Administration of GnRH analogue with hMG for 12 days did not affect E(2) levels. Both women were given estrogen-progestin replacement therapy. Inhibin B has a diagnostic role in women with gonadotropin-resistant ovary syndrome associated with secondary amenorrhea. A review of the literature confirms the uniqueness of the diagnostic role of inhibin B in these cases.

Allelic imbalance in hMLH1 or BRCA2 loci associated with response of cervical and endometrial cancer to radiotherapy.

Effectiveness of radiotherapy is influenced by several genetic properties of the targeted cells. The aim of this study was the identification of prognostic indicators of tumor response to radiation in cervical and endometrial cancer. Using microsatellite DNA analysis, we investigated 31 markers, located on 1p, 2p, 2q, 3p, 9p, 9q, 13q, 17p and 17q for genomic alterations in 37 cervical and 21 endometrial cancer cases, with complete follow-up data. Genetic alterations of the initial tumor genotypes were observed after radiation in 86.5% of cervical and 81.0% of endometrial cases. Reversions to the original normal genotype were observed in 40.5 and 28.6% respectively, predominantly in cured patients rather than in recurred cases. Survival curves by the Kaplan-Meier method showed a worse prognosis for cervical cancer patients whose tumors harbor allelic imbalance (AI) on 3p or 13q, and for endometrial cancer patients whose tumors harbor AI on 13q. Our data suggest a possible association of the hMLH1 or BRCA2 genes, implicated in distinct DNA repair pathways and located on 3p and 13q respectively, with response of cervical and endometrial cancer to radiotherapy. Moreover, microsatellite DNA analysis before and after radiation treatment could be used as a marker of the clinical outcome of patients.

Frequent loss of heterozygosity in chromosomal region 9pter-p13 in tumor biopsies and cytological material of uterine cervical cancer.

Using polymerase chain reaction-based microsatellite analysis we examined 40 cases, tumor biopsies and cytological material, of early stage cervical cancer and 20 healthy donors. Loss of heterozygosity (LOH) was detected in 35 out of 40 cases (87.5%), located on 9pter-p13 (67.5%), 9q32-34 (17.5%), 13q12 (32.5%), 17p13 (0%) and 17q11-q22 (12.5%). Microsatellite instability (MIN) phenotype was found in three out of 40 cases (7.5%). The accuracy in LOH and MIN detection in cytological material compared to tumor biopsies was 91.5 and 86.0%, respectively. None of the specimens of healthy donors exhibited any genetic alteration. Our data suggest that microsatellite analysis in cytological material could be used for the early detection of cervical cancer.

K-ras mutations and HPV infection in cervicitis and intraepithelial neoplasias of the cervix.

Activation of ras genes and human papilloma virus (HPV) infection have been extensively described in cervical carcinomas while information concerning their implication in premalignant lesions of the cervix is limited. We investigated the incidence of K-ras codon 12 point mutations and HPV infection in cases of cervicitis and cervical intraepithelial neoplasias (CIN). Forty-seven cases of women with cervicitis or CIN were examined for the presence of K-ras mutations and HPV infection using PCR-RFLP methodology. Furthermore, HPV typing was carried out in HPV positive samples by multiplex PCR. K-ras mutations were detected in 7/47 cases (15%) while HPV genome was found in 17/47 cases (36%). HPV typing revealed HPV-18 at a higher rate than HPV-16 (71% vs 29%). No statistically significant association was observed between the presence of K-ras mutations, HPV infection and clinical parameters or smoking-alcohol habits. Our results suggest that mutational activation of K-ras gene is implicated in the development of premalignant cervical lesions and HPV infection may be an important step in the development of premalignant cervical lesions.