Showing papers on "Cervix published in 2001"

Overexpression of p16INK4A as a specific marker for dysplastic and neoplastic epithelial cells of the cervix uteri

Abstract: Cytological screening for cervical cancer or its precursors using Papanicolaou's smear test (Pap test) has been highly efficient to reduce the morbidity and mortality of cervical cancer. However, evaluation of the Pap test relies on subjective diagnostic parameters and is affected by a high rate of false-positive and false-negative results. More objective diagnostic parameters to identify truly dysplastic or neoplastic cells in cervical smears as well as in cervical biopsy samples would therefore avoid insecurity for many patients and the high screening costs associated with repeated testing. Cervical dysplasia is induced by persistent infections through high-risk types of human papillomaviruses (HPVs). Outgrowth of dysplastic lesions is triggered by increasing expression of two viral oncogenes, E6 and E7, which both interact with various cell cycle-regulating proteins. Among these is the retinoblastoma gene product pRB, which is inactivated by E7. pRB inhibits transcription of the cyclin-dependent kinase inhibitor gene p16INK4a. Increasing expression of the viral oncogenes in dysplastic cervical cells might thus be reflected by increased expression of p16INK4a. In line with this hypothesis, we observed marked overexpression of p16INK4a in all cervical intraepithelial neoplasm (CIN) I lesions (n = 47) except those associated with low-risk HPV types (n = 7), all CIN II lesions (n = 32), all CIN III lesions (n = 60) and 58 of 60 invasive cervical cancers. In contrast, no detectable expression of p16INK4a was observed in normal cervical epithelium (n = 42), inflammatory lesions (n = 48) and low-grade cervical lesions (CIN I) associated with low-risk HPV types (n = 7). Dysplastic cells could also be identified in cervical smears using a specific p16INK4a monoclonal antibody. These data demonstrate that p16INK4a is a specific biomarker to identify dysplastic cervical epithelia in sections of cervical biopsy samples or cervical smears. © 2001 Wiley-Liss, Inc.

Lymph Node Staging by Positron Emission Tomography in Patients With Carcinoma of the Cervix

Abstract: PURPOSE: The aim of this study was to compare the results of computed tomography (CT) and positron emission tomography (PET) with [18F]-fluoro-2-deoxy-d-glucose (FDG) for lymph node staging in patients with carcinoma of the cervix and to evaluate the relationship of the imaging findings to prognosis. PATIENTS AND METHODS: We retrospectively compared the results of CT lymph node staging and whole-body FDG-PET in 101 consecutive patients with carcinoma of the cervix. Patients were treated with standard irradiation and chemotherapy (as clinically indicated) and observed at 3-month intervals for a median of 15.4 months (range, 2.5 to 30 months). Progression-free survival was evaluated by the Kaplan-Meier method. RESULTS: CT demonstrated abnormally enlarged pelvic lymph nodes in 20 (20%) and para-aortic lymph nodes in seven (7%) of the 101 patients. PET demonstrated abnormal FDG uptake in pelvic lymph nodes in 67 (67%), in para-aortic lymph nodes in 21 (21%), and in supraclavicular lymph node in eight (8%). Th...

Preinduction sonographic measurement of cervical length in the prediction of successful induction of labor.

Abstract: Background Induction of labor is carried out in approximately 20% of pregnancies. However, approximately 20% of women having induction of labor end up having a Cesarean delivery. The traditional method of predicting whether an induced labor will result in successful vaginal delivery is based on the preinduction ‘favorability’ of the cervix as assessed by the Bishop score. However, this assessment is subjective and several studies have shown a poor predictive value for the outcome of induction. Objectives To examine the relationship between preinduction sonographically measured cervical length and the Bishop score and to compare the two measurements in the prediction of successful vaginal delivery within 24 h of induction. Methods In this multicenter study, preinduction cervical assessment was undertaken in 240 women with singleton pregnancies at 37–42 weeks of gestation. The Bishop score was assessed by digital examination and the cervical length was measured by transvaginal sonography. Results Multiple regression analysis demonstrated that cervical length, Bishop score and parity provided independent contribution in the prediction of the likelihood of delivering vaginally within 24 h. Further examination of the different components of the Bishop score showed that only cervical length provided a significant contribution in the prediction of the likelihood of vaginal delivery within 24 h. In the receiver operating characteristic curves, the best cut-off point for the prediction of successful induction was 28 mm for cervical length and 3 for the Bishop score. However, cervical length appears to be a better predictor than the Bishop score, with a sensitivity of 0.87 and a specificity of 0.71 compared to 0.58 and 0.77, respectively. Similarly, the Kaplan–Meier survival curves indicate that better discriminatory results in the prediction of vaginal delivery within 24 h are achieved using cervical length rather than the Bishop score. Conclusion Transvaginal sonographic measurement of cervical length provides a useful prediction of the likelihood of vaginal delivery within 24 h of induction.Copyright © 2001 International Society of Ultrasound in Obstetrics and Gynecology

Human papillomavirus 16 and 18 L1 serology compared across anogenital cancer sites.

Abstract: Human papillomavirus (HPV) DNA has been detected in the great majority of cancers of the uterine cervix and anus, whereas the association of HPV DNA with cancer at other anogenital sites has produced less consistent results. This study was designed to compare HPV exposure among anogenital cancer cases and matched controls. Cases (1782) of anogenital cancer diagnosed in the Seattle area from 1978 to 1998 were identified and interviewed. Their responses were compared with those of 2383 age- and sex-matched controls. Blood was drawn at interview from both cases and controls and tested for antibodies to HPV-16 and HPV-18. Tissue blocks were tested for HPV DNA for 649 cases. Serum antibodies to HPV-16 were associated with in situ and invasive cancer at all sites among men and women with the exception of in situ penile cancer. Anti-HPV-18 antibodies were associated with cancers at all sites among women. The increased risk of cancer associated with HPV-16 seropositivity ranged from odds ratio = 1.8 (95% confidence interval, 1.4-2.5) for adenocarcinoma of the cervix to odds ratio = 5.9 (95% confidence interval, 3.4-10.3) for anal cancer in men. Associations between seroprevalence and cancers were stronger when analyses were restricted to HPV-16- or HPV-18 DNA-positive cases. HPV DNA was detected in >80% of cancers from all sites tested. HPV-16 DNA was the type most frequently detected at all sites (range, 40.9-82.2%). HPV-18 DNA was detected in 44.7% of adenocarcinomas of the cervix but detected much less often (2.6-18.1%) at other sites. These findings support an important role for HPV infection in anogenital cancer at all sites. Differences in the proportion of seropositives among HPV-16 DNA-positive cases by site suggest either that the immune response varies by site or that cancer development may lead to changes in antibody responses in a site-specific fashion.

HPV DNA Testing of Self‐Collected Vaginal Samples Compared With Cytologic Screening To Detect Cervical Cancer

Abstract: JAMA 2000;283:81–6 This study was conducted to determine whether self-collection of vaginal secretions with a Dacron swab for HPV DNA (Hybrid Capture II HPV DNA Assay, Digene Corp, Beltsville, MD) was comparable to a Pap smear collected by a certified nurse for the detection of advanced cervical intraepithelial neoplasia (CIN) and cervical cancer in 1,415 black South African women. After being tested with the swab and by a certified nurse, acetic acid was applied to the cervix and a cervical photograph (Cervigram, National Testing Laboratories Inc.) was obtained. Women with abnormal results were referred for colposcopy. CIN2 or CIN3 was found in 47 (3.4%) of 1,365 adequately assessed women and 9 cases of invasive cancer. Of women with CIN2 or CIN3, 66% were identified by the Dacron swab/DNA technique; 68% were identified from an abnormal conventional smear. The false positive rate for the HPV DNA technique was 17% and for the Pap smear 12%. The study indicates HPV testing is as sensitive but less specific than the Pap smear. Comment: The authors clearly state the context of this study is that in the United States half the women diagnosed with cervical cancer have not had a Pap smear in the preceding 3 years. In the many parts of the rest of the world, the access to care may be even more limited. HPV screening, in their opinion, can be used to offer a new way to increasing screening in areas without caregivers to obtain the smear or cytologists to interpret them. (TMJ)

Nasal and Vaginal Vaccinations Have Differential Effects on Antibody Responses in Vaginal and Cervical Secretions in Humans

Abstract: Sexually transmitted diseases are a major health problem worldwide, but there is still a lack of knowledge about how to induce an optimal immune response in the genital tract of humans. In this study we vaccinated 21 volunteers nasally or vaginally with the model mucosal antigen cholera toxin B subunit and determined the level of specific immunoglobulin A (IgA) and IgG antibodies in vaginal and cervical secretions as well as in serum. To assess the hormonal influence on the induction of antibody responses after vaginal vaccination, we administered the vaccine either independently of the stage in the menstrual cycle or on days 10 and 24 in the cycle in different groups of subjects. Vaginal and nasal vaccinations both resulted in significant IgA and IgG anti-cholera toxin B subunit responses in serum in the majority of the volunteers in the various vaccination groups. Only vaginal vaccination given on days 10 and 24 in the cycle induced strong specific antibody responses in the cervix with 58-fold IgA and 16-fold IgG increases. In contrast, modest responses were seen after nasal vaccination and in the other vaginally vaccinated group. Nasal vaccination was superior in inducing a specific IgA response in vaginal secretions, giving a 35-fold increase, while vaginal vaccination induced only a 5-fold IgA increase. We conclude that a combination of nasal and vaginal vaccination might be the best vaccination strategy for inducing protective antibody responses in both cervical and vaginal secretions, provided that the vaginal vaccination is given on optimal time points in the cycle.

US of the pediatric female pelvis: a clinical perspective.

Abstract: When investigating pelvic pathologic conditions in female pediatric patients, one needs to be aware of the developmental changes that take place around puberty. The prepubertal uterus is thin, with a fundus equal in size to the cervix. Owing to the hormonal stimulation of puberty, the uterus enlarges and the fundus becomes prominent. The ovaries are demonstrated with ultrasonography (US) at all ages. Ovarian volume increases after 6 years of age. Microcystic follicles are normally seen throughout childhood. US is the modality of choice for imaging the pediatric female pelvis. The main indications for pelvic US in the pediatric age group are pubertal precocity or pubertal delay, pelvic pain or pelvic masses, and ambiguous genitalia. Vaginal bleeding in the prepubertal child can be due to a vaginal foreign body, vaginal rhabdomyosarcoma, or precocious puberty. Common causes of primary amenorrhea in teenagers include gonadal dysgenesis (Turner syndrome) and mullerian (uterovaginal) anomalies. Pelvic pain or ...

Cyclooxygenase-2 expression and prostaglandin E2 synthesis are up-regulated in carcinomas of the cervix : A possible autocrine/paracrine regulation of neoplastic cell function via EP2/EP4 receptors

Abstract: The prevalence of cervical cancer in South African women is reported as being the highest in the world, occurring, on the average, in 60 of every 100,000 women. Cervical cancer is thus considered an important clinical problem in sub-Saharan Africa. Recent studies have suggested that epithelial tumors may be regulated by cyclooxygenase (COX) enzyme products. The purpose of this study was to determine whether cyclooxygenase-2 (COX-2) expression and PGE2 synthesis are up-regulated in cervical cancers. Real-time quantitative RT-PCR and Western blot analysis confirmed COX-2 ribonucleic acid and protein expression in all cases of squamous cell carcinoma (n = 8) and adenocarcinoma (n = 2) investigated. In contrast, minimal expression of COX-2 was detected in histologically normal cervix (n = 5). Immunohistochemical analyses localized COX-2 expression and PGE2 synthesis to neoplastic epithelial cells of all squamous cell (n = 10) and adenocarcinomas (n = 10) studied. Immunoreactive COX-2 and PGE2 were also coloca...

Elevated cyclooxygenase-2 expression correlates with diminished survival in carcinoma of the cervix treated with radiotherapy.

Abstract: Purpose: The purpose of this study was to examine the relationship between overall survival and prognostic factors in carcinoma of the cervix treated with radiation therapy. A clinicopathologic study was performed on 24 patients. Methods and Materials: Formalin-fixed, paraffin-embedded tumor biopsies were stained for Cyclooxygenase-2 (COX-2), Topoisomerase I, Topoisomerase II, and p53. Clinical factors such as stage, grade, tumor size, pre- and post-treatment hemoglobin level, and radiotherapy dose were also evaluated. Results: Median follow-up was 75 months for living patients. The only immunohistochemical or clinical factor that was associated with improved survival was decreased COX-2 distribution staining. High COX-2 distribution staining was associated with decreased overall survival ( p = 0.021) and decreased disease-free survival ( p = 0.015) by log-rank comparison of Kaplan-Meier survival curves. The 5-year overall survival rates for tumors with low vs. high COX-2 distribution values were 75% and 35%, respectively. COX-2 staining intensity was found to correlate positively with tumor size ( p = 0.022). Conclusion: These findings indicate that increased expression of COX-2 portends a diminished survival in patients with invasive carcinoma of the cervix treated with radiotherapy. Because COX-2 is an early-response gene involved in angiogenesis and inducible by different stimuli, these data may indicate opportunity to intervene with specific inhibitors of COX-2 in carcinoma of the cervix.

Evolution of cervical abnormalities among women with HIV-1: evidence from surveillance cytology in the women's interagency HIV study.

Abstract: Objective: To determine incidence, progression, and regression rates for abnormal cervical cytology and their correlates among women with HIV. Methods: In a multicenter prospective cohort study conducted October 1, 1994, through September 30, 1999 at university, public, and private medical centers and clinics, 1639 HIV-seropositive and 452 seronegative women were evaluated every 6 months for up to 5 years using history, cervical cytology, T-cell subsets, and quantitative plasma HIV RNA. Human papillomavirus (HPV) typing at baseline was determined by polymerase chain reaction. Cytology was read using the Bethesda system, with any smear showing at least atypia considered abnormal. Poisson regression identified factors associated with incident cytologic abnormalities whereas logistic regression identified those associated with progression and regression after an abnormality. Results: At least one abnormal smear was found during all of follow-up among 73.0% of HIV-seropositive patients and 42.3% of seronegatives (p 200/mm 3 and HIV RNA levels <4000/ml of similar HPV status. Conclusions: Although HIV infected women were at high risk for abnormal cytology, high-grade changes were uncommon. HIV status, HPV detection, CD4 lymphocyte count, and HIV RNA level predicted the incidence of cervical cytologic abnormalities. Progression was significantly increased only among the most immuno-suppressed women, while regression was significantly reduced in all HIV seropositive women except those with the best controlled HIV disease.

The role of mast cell tryptase in neoangiogenesis of premalignant and malignant lesions of the uterine cervix.

Abstract: Recently, mast cell tryptase has been identified as another potent proangiogenic factor in tumors, along with fibroblast and vascular endothelial growth factors. Its role has been studied in a number of cancers, including carcinoma of the uterine cervix, with discordant results. Our aim was to study the expression of tryptase and bFGF in mast cells (MCs) during development of neoangiogenesis in premalignant and malignant lesions of the cervix. Biopsy specimens from 21 patients without cancer and from 63 patients with dysplasias and squamous cell carcinomas were used. They were stained with Alcian blue– safranin O (ABSO) and immunostained with specific antibodies against factor VIII, CD105, tryptase, and bFGF. Tryptase-positive mast cells increased with tumor progression and were close to newly formed blood vessels. Vascularization showed a linear increase from dysplasia to invasive cancer. We suggest that MC tryptase may upregulate neoangiogenesis in carcinogenesis of the uterine cervix. (J Histochem Cyto...

Papanicolaou smear sensitivity for the detection of adenocarcinoma of the cervix: a study of 49 cases.

Abstract: BACKGROUND Papanicolaou smear sensitivity for cervical adenocarcinoma (CVCA) is not well established. Also uncertain are the relative contributions to falsely negative diagnoses of sampling, screening, and interpretive errors. METHODS Papanicolaou smears were identified from all patients at our institutions with biopsy-proven cervical adenocarcinoma from 1988–1998. All available negative and unsatisfactory smears were reviewed. RESULTS Of 49 patients with CVCA, 66 smears initially diagnosed as negative and 4 smears initially diagnosed as unsatisfactory from 30 patients were identified. Thirty-two negative smears and 4 unsatisfactory smears from 19 patients were available for review. The retrospective diagnoses in the cases initially called negative were: unsatisfactory in 2, negative in 15, and atypical glandular cells consistent with either adenocarcinoma in situ (AIS) or CVCA in 15. Three of four smears initially called unsatisfactory had neoplastic glandular cells identified retrospectively. The 18 falsely negative or falsely unsatisfactory smears were from 13 patients obtained up to 5 years before biopsy diagnosis. These smears contained neoplastic cells likely to have been mistaken for lower segment endometrial cells (LUS) or endocervical cells with tubal metaplasia (TM) in 11, reactive endocervical cells in 6, and both in 1. In 16 of the 18 smears, the abnormal cells were abundant, although preservation was suboptimal in 6. CONCLUSIONS Sensitivity of a single Papanicolaou smear for CVCA was between 45% and 76% depending on the classification of negative slides that were not available for review, comparable to previously reported sensitivity for AIS. The diagnostic false-negative or false-unsatisfactory rate in reviewed smears was 50% (18 of 36). Diminished sensitivity is due to the under recognition of glandular neoplasia resembling LUS, TM, or reactive endocervical cells. Cancer (Cancer Cytopathol) 2001;93:8–15. © 2001 American Cancer Society.

Cervical assessment at the routine 23‐week scan: standardizing techniques

Abstract: Objective To examine the frequency of curvature of the cervix and to establish the degree of curvature with increasing cervical length. To assess the significance of this phenomenon in terms of the classification of patients as high risk for pre-term delivery. Method Cervical length was measured prospectively by transvaginal sonography in 301 women at 23 weeks of gestation. The distance between the internal and external os was measured both as a straight line and also as a curved line along the endocervical canal. In addition, a search of our database was made to identify all women who had undergone cervical assessment as part of a policy of routine screening. In those with cervical length of less than 26 mm the thermal images of the cervix were used to obtain straight and curved measurements. The frequency of curved cervix was calculated and the relationship between the ratio of straight to curved measurement to the curved one was determined. Results In the prospective study curvature of the cervix was observed in 143 (48%) of the 301 women. Curvature was observed in 51% (135 of 267) with cervical length of 26–55 mm, 25% (8 of 32) with length of 16–25 mm, and none of the two with length of 1–15 mm. The ratio of the straight to the curved measurement decreased with increasing cervical length (r = −0.27, P = 0.001). In the retrospective study curvature of the cervix was found in 72 (15%) of 471 with length of 16–25 mm and in none of the 76 with length of 1–15 mm. Conclusion Cervical length is influenced by the degree of cervical curvature. The disparity of measurements between the internal and external os taken as a straight line or along the cervical canal increases with cervical length. However, this disparity may not have any clinical implications because at short cervical length (less than 16 mm) the cervix appears to be always straight. Copyright © 2001 International Society of Ultrasound in Obstetrics and Gynecology

Cervical cancer in Canada: changing patterns in incidence and mortality.

Abstract: Data on incidence of cervical cancer by histologic subtype and mortality for the Canadian provinces of Ontario, Saskatchewan, and British Columbia were used to examine time trends by age, calender period, and birth cohort Age-adjusted incidence rate of squamous cell carcinoma of the cervix decreased from 111 per 100,000 women in 1970-72 to 53 in 1994-96, while the rate for cervical adenocarcinoma increased from 11 per 100,000 women to 15 over the same period Age-adjusted mortality rate declined from 79 per 100,000 women in 1953-55 to 19 in 1995-97 The patterns in age-specific mortality rates in 1953-72 were different from those in 1973-97; younger women experienced larger reductions in mortality during the earlier period while older women benefited to a greater extent during the latter period Age-period-cohort modeling showed that cohort effects were responsible for the decreasing trends in incidence of squamous cell carcinoma of the cervix and increasing trends in adenocarcinoma, and both period and cohort effects account for the observed trends in mortality The results suggest that Pap smear screening has played a significant role in the reduction in squamous cell cervical carcinoma The causes for the increase in cervical adenocarcinoma are unclear

Human papillomavirus variants and squamous neoplasia of the cervix.

Abstract: Human papillomaviruses (HPVs) play a central role in the aetiology of cervical neoplasia. However, only a small proportion of cervical intraepithelial lesions infected with high-risk HPVs will progress to invasive cervical carcinoma, which indicates the involvement of additional factors. An important emerging viral factor is naturally occurring intratypic sequence variation. Such variation has been used to study the geographical spread of HPVs, but there is increasing evidence that it may be important in determining the risk of development of neoplastic disease. The collected data indicate that different HPV variants have altered biochemical and biological properties and represent an additional risk factor in the development of squamous intraepithelial lesions and invasive carcinoma of the cervix. This may be relevant not only to the biology of HPV infection and its association with squamous neoplasia, but also to the use of HPV typing in clinical practice.

Surrogate biomarkers of HPV infection in cervical neoplasia screening and diagnosis.

Abstract: The current prevention of cervical cancer and elimination of its precursors is predicated on the identification of cervical cytologic abnormalities and their histologic confirmation. This strategy, although effective, depends on both sensitivity and specificity of cytology and precise histologic distinction between precursor lesions and their mimics during biopsy interpretation. The effective application of diagnostic criteria is operator dependent and varies as a function of experience and training. However, because human papilloma viruses (HPV) are causative agents and alter the cell cycle in cervical neoplasms, host genes interacting directly or indirectly with HPV oncoproteins have been identified in vitro. Recent research has centered on identifying the host genes upregulated in association with HPV infection, determining their suitability as "surrogate markers" for HPV infection, and using these markers to identify HPV-associated epithelial lesions in tissue or cytologic specimens. This review surveys recent advances in this field, summarizing the advantages and limitations of several candidate biomarkers, including PCNA, Ki-67, cyclin E, p16ink4, MN antigen, carcinoembryonic antigen (CEA), and telomerase in the recognition of preinvasive cervical neoplasia, and discusses their future potential in cervical cancer screening. Based on current studies, the strongest candidates for diagnosis and screening are p16 and cyclin E (squamous) and MN (glandular) biomarkers. As new genes are identified and tested, the concept of biomarkers as tools in primary screening and lesion recognition will continue to mature.

Histologic subtype has minor importance for overall survival in patients with adenocarcinoma of the uterine cervix: a population-based study of prognostic factors in 505 patients with nonsquamous cell carcinomas of the cervix.

Abstract: BACKGROUND The incidence of adenocarcinoma of the uterine cervix is increasing For better prognostic information, the authors studied all nonsquamous cell carcinomas (non-SCCs) in the Norwegian population over a total of 15 years METHODS All non-SCCs from three 5-year periods (1966–1970, 1976–1980, and 1986–1990) were reviewed and classified according to the World Health Organization classification system, and histopathologic and clinical parameters were registered Tissue blocks were available from all patients RESULTS Of 505 patients, 417 had tumors classified as adenocarcinoma, and 88 had tumors classified as other non-SCC The mean ages were 53 years and 52 years for patients with adenocarcinoma and non-SCC, respectively Sixty-two percent of the staged patients had clinical Stage I disease according to the classification system of the International Federation of Gynecology and Obstetrics (FIGO) In univariate analyses, histology, architectural and nuclear grade, extension to the vagina or corpus uteri, tumor length (> 20 mm) or tumor volume (> 3000 mm3), infiltration depth (in thirds of the cervical wall), thickness of the remaining wall (< 3 mm), vascular invasion, lymph node metastases, treatment, and patient age were significant variables in patients with FIGO Stage I disease Variables with no significance in patients with Stage I disease were number of mitoses, state of resection margins, infiltration to ectocervix, tumor thickness, lymphoid reaction, earlier or concomitant cervical intraepithelial neoplasia, stump carcinoma, DNA ploidy or DNA index, or time period Multivariate analyses of patients with FIGO Stage I disease identified small cell carcinoma, corpus infiltration, vascular invasion, and positive lymph nodes as independent prognostic factors CONCLUSIONS Small cell carcinoma was the only histologic subgroup of independent importance for prognosis in patients with non-SCC of the uterine cervix No significant difference between major subtypes of adenocarcinoma favored a simplified classification Extension to the corpus in patients with early-stage disease was of independent significance and should be acknowledged in planning treatment Cancer 2001;92:2471–83 © 2001 American Cancer Society

Human papillomaviruses and their role in cervical cancer.

Abstract: Human papillomaviruses (HPVs) have been linked to a variety of human diseases, most notably cancer of the cervix, a disease responsible for at least 200,000 deaths per year worldwide. Over 100 different types of HPV have been identified and these can be divided into two groups. Low-risk HPV types are the causative agent of benign warts. High-risk HPV types are associated with cancer. This review focuses on the role of high-risk HPV types in cervical tumorigenesis. Recent work has uncovered new cellular partners for many of the HPV early proteins and thrown light on many of the pathways and processes in which these viral proteins intervene. At the same time, structural and biochemical studies are revealing the molecular details of viral protein function. Several of these new avenues of research have the potential to lead to new approaches to the treatment and prevention of cervical cancer.

Human Papillomavirus and Long-term Oral Contraceptive Use Increase the Risk of Adenocarcinoma in Situ of the Cervix

Abstract: We examined United States Surveillance, Epidemiology, and End Results incidence data and conducted a population-based case-control study to examine the role of human papillomavirus (HPV) and oral contraceptive (OC) use in the etiology of adenocarcinoma in situ of the cervix (ACIS). One hundred and fifty women diagnosed with ACIS and 651 randomly selected control women completed in-person interviews. The presence of HPV DNA in archival ACIS specimens was determined by E6 and L1 consensus PCR. Serum samples from case and control subjects were collected at interview, and antibodies to HPV-16 L1 and HPV-18 L1 were detected by virus-like particle capture assays. The overall prevalence of HPV DNA was 86.6%, with 39.0% positive for HPV-16 DNA, 52.4% positive for HPV-18 DNA, and 13.4% positive for more than one HPV type. The age-adjusted relative risk of ACIS associated with HPV-18 seropositivity was 3.3 (95% confidence interval 2.2-4.9). No increased risk was associated with antibodies to HPV-16 L1. Among women born after 1945, the relative risk increased with duration of OC use, with the highest risk for 12 or more years of use (odds ratio, 5.5; 95% confidence interval, 2.1-14.6) relative to nonusers. The detection of HPV DNA in 86.6% of ACIS and the strong association of ACIS with HPV-18 L1 seropositivity underscore the importance of HPV, particularly HPV-18, in the etiology of ACIS. In addition, long-term OC use may contribute to the pathogenesis of these tumors in some women.

Sentinel node procedure in Ib cervical cancer: a preliminary series

Abstract: The aim of this study was to determine the diagnostic accuracy and feasibility of sentinel lymph node (SLN) detection using a gamma probe in patients with Figo IB cervical cancer. Between January 1999 and September 2000, 14 patients with cervical cancer, planned for radical hysterectomy were eligible for the study. The day before radical hysterectomy we injected technetium99m-labelled nanocolloid in each quadrant of the cervix. Dynamic and static images were recorded using a gamma camera. SLNs were identified intraoperatively using a handheld gamma-detection probe. After resection of SLNs a standard radical hysterectomy with pelvic lymph node dissection was performed. Patients and tumour characteristics were compared with sentinel node detection and with final histopathological and immunohistochemical results. Scintigraphy showed focal uptake in 13 of the 14 patients. Intraoperatively we detected 26 sentinel nodes by gamma probe. In 8 of 13 patients, one or more sentinel nodes were identified unilaterally, in 5 women bilaterally. Histologically positive SLNs were found in only 1 patient. We did not find any false-negative SLN in our series. In conclusion identification of sentinel nodes in cervical cancer is feasible with preoperatively administered technetium99m-labelled nanocolloid. A larger series will be required to establish sentinel node detection in cervical cancer for further therapy concepts and planning. © 2001 Cancer Research Campaignhttp://www.bjcancer.com

Cervical Ectopy in Adolescent Girls with and without Human Immunodeficiency Virus Infection

Abstract: The objective of this study was to examine factors, including human immunodeficiency virus (HIV) infection, associated with ectopy among adolescent girls aged 12‐20 years who were participating in an ongoing study of HIV infection in adolescents. Samples for detection of bacterial vaginosis, Chlamydia trachomatis, and Neisseria gonorrhoeae and a high-resolution photograph of the cervix for ectopy measurement were collected. Ectopy data for 189 and 92 HIV-positive and -negative adolescents, respectively, were examined. Although univariate analysis found HIV infection and oral contraceptive use to be associated with the amount of ectopy, multivariate logistic regression analysis showed that only number of lifetime sex partners was a significant predictor, with more partners associated with less ectopy (odds ratio, 0.47; 95% confidence interval, 0.22‐1.00; ). In summary, adolescent girls with greater P p .05 numbers of lifetime sex partners were more likely to have mature cervixes (less ectopy). HIV infection was not independently associated with ectopy. “Ectopy” refers to the area of the ectocervix lined by columnar epithelium. Columnar epithelium lines the endocervix and, in many women, extends onto the proximal portion of the cervix immediately adjacent to the multilayer squamous epithelium, forming a visible squamocolumnar junction. Because of its thin, vascularized epithelium, the area of ectopy is fragile, and blood vessels lie in close contact with the vaginal environment [1]. This creates easy access to blood and lymphatic systems, possibly diminishing mucosal barriers to sexually transmitted infections. Several studies have shown that the area of cervical ectopy, or cervical immaturity, is associated with increased risk for human