Management of Cervical Ectopic Pregnancies: A Scoping Review.

OBJECTIVE: To investigate published cases of cervical ectopic pregnancy between 2000 and 2018 and compare management strategies and treatment success rates based on initial patient characteristics. METHODS: PubMed, EMBASE, and Web of Science were searched to capture peer-reviewed citations published between 2000 and 2018. Cases reporting either ß-hCG level, crown-rump length, or gestational sac diameter for each individual patient were included. Data regarding the article information, patient characteristics, treatment used, and outcomes were collected. Initial success was defined as resolution of the cervical ectopic pregnancy with the predefined treatment plan. Initial failure was defined as the requirement of additional unplanned interventions due to the predefined treatment plan not being successful. End success was defined as resolution of the cervical ectopic pregnancy without hysterectomy. RESULTS: A total of 204 articles from 44 countries comprising 454 cases were reviewed. The initial ß-hCG level ranged from 9 to 286,500, with a median of 14,773, and gestational age ranged from 4 to 18 weeks, with an average of 7 4/7 weeks (±2 0/7 weeks). In looking at initial success, compared with methotrexate alone, dilation, and curettage (odds ratio [OR] 2.26; 95% CI 2.64-10.45), dilation and curettage combined with uterine artery embolization (OR 4.85; 95% CI 2.06-11.44) and uterine artery embolization (OR 5.17; 95% CI 1.14-23.53) were more effective options. More than half of patients (50.2%) required multiple interventions, and 41 (9%) resulted in hysterectomy. CONCLUSIONS: Management of cervical ectopic pregnancies should be guided by patient stability, ß-hCG level, size of pregnancy, and fetal cardiac activity but may benefit from a planned multimodal approach.

Impact of additional risk factors on the incidence of preterm delivery among pregnant women diagnosed with short cervix.

OBJECTIVE: Additional risk factors for preterm delivery in pregnant women with cervical shortening are not fully understood; however, mid-trimester cervical shortening is accepted as a risk factor for preterm delivery. This study aimed to identify risk factors associated with subsequent preterm delivery among patients with short cervix detected after late mid-trimester. MATERIALS AND METHODS: This was a retrospective study of medical data from a single perinatal tertiary facility. We identified 134 asymptomatic women with singleton pregnancies where cervical shortening (≤25 mm) was detected during routine universal screening at 22-33 weeks. Statistical analyses were conducted to identify causal relationships between the incidence of preterm delivery and known risk factors for preterm delivery. RESULTS: Incidence of preterm delivery was 27.6% (37/134) and preterm premature rupture of membrane was preceded in 46.0% (17/37) of the women with preterm delivery. Using logistic regression analysis, we identified uterine contractions [aOR 4.25, 95% confidence intervals (CI):1.68-12.1] and increased C-reactive protein (CRP) and increased white blood cell (WBC) in blood test (CRP: aOR 3.45, 95% CI:1.50-9.71; WBC: aOR 1.28, 95% CI: 1.08-1.55) as risk factors which significantly increased the risk of preterm delivery among women diagnosed with short cervix. Preterm delivery occurred in 91% of women positive for both uterine contractions and CRP >0.5 mg/dl. CONCLUSIONS: Uterine contraction and elevated CRP were additional risk factors for preterm delivery among women with short cervix. These results might be clinically useful to evaluate subsequent risk for preterm delivery in asymptomatic pregnant women presenting with short cervix in mid-pregnancy.

Plasma expression of miRNA-21, - 214, -34a, and -200a in patients with persistent HPV infection and cervical lesions.

BACKGROUND: To examine differences in the plasma levels of miRNA-21, - 214, -34a, and -200a in patients with persistent high-risk human papillomavirus (hr-HPV) infection or with cervical lesions of different grades. METHODS: Venous blood was collected from 232 individuals to measure the plasma expression levels of miRNA-21, - 214, -34a, and -200a. The subjects included normal controls and patients with persistent hr-HPV infection, CIN1, CIN2, CIN3, or cervical cancer (n = 42, 31, 19, 54, 71, and 15 patients, respectively). Cervical conization specimens were collected from all the women. To ensure the accuracy of histopathology, three consecutive tissue sections with an identical diagnosis were selected, and dissection samples were taken from them for miRNA detection. Eligible cases met the inclusion criteria based on sample observation using the middle slice of sandwich tissue sections from the pathological tissue in accordance with the diagnosis of CIN1, CIN2 and CIN3 in 8, 29, and 26 cases, respectively. The miRNA-21, - 214, -34a, and -200a expression levels in the paraffin-embedded tissue samples were determined. The percentage of patients with a CIN2+ diagnosis at 30-49 years old was significantly different from that of those diagnosed with CIN1. The incidence of CIN2+ patients exposed to passive smoking was significantly different from that of CIN1- patients. The percentage of CIN2+ patients with three pregnancies was significantly different from that of those with CIN1, and the percentage of CIN2+ subjects with ≥4 pregnancies was significantly different from that of CIN1- patients. The number of CIN2+ patients with two or more induced abortions was significantly different from that of patients with CIN1. The percentage of CIN2+ patients who underwent a caesarean section was significantly different from that of patients with CIN. The percentage of CIN2+ patients with first-degree relatives with cancer was significantly different from that of those with CIN1. Among CIN2+ patients, the percentage with a first sexual encounter at ≤20 years old was significantly different from that of those with CIN1. The percentage of CIN2+ patients with ≥2 sexual partners was significantly different from that of CIN1- patients. RESULTS: The plasma miRNA-214, -34a, and -200a expression levels were decreased in patients with more severe cervical lesions. Plasma miRNA levels in CIN1- patients were significantly different from those in CIN2+ patients. The kappa values for miRNA-21, - 214, -34a and -200a in tissue versus plasma were 0.7122, 0.9998, 0.8986 and 0.7458, respectively. The sensitivity of each biomarker for detecting CIN2 was calculated, and ROC curves of the four miRNA biomarkers were drawn. The AUC of the four plasma miRNAs was greater than 0.5, with the AUC of miRNA-21 being the largest at 0.703. The plasma miRNA expression levels exhibited at least one tie between CIN1 and CIN2. The AUCs for miRNA-21, -34a, -200a and - 214 were 0.613, 0.508, 0.615 and 0.505, respectively. CONCLUSIONS: Changes in plasma miRNA-21, - 214, -34a and -200a levels were associated with cervical lesion severity. The plasma miRNA levels in CIN1- subjects were significantly different from those in CIN2+ subjects. This analysis may help in detection of high-grade cervical lesions.

Trends in HPV cervical and seroprevalence and associations between oral and genital infection and serum antibodies in NHANES 2003-2012.

BACKGROUND: HPV infects multiple sites in the epithelium, including the genitals and oral cavity. The relation between genital and oral infections and serum antibodies can help explain the natural history and epidemiology of HPV. METHODS: We analyzed HPV data from NHANES derived from self-collected vaginal swabs (women ages 14-59, 2003-12), oral rinses (men and women 14-69, 2009-12), and serum (men and women 14-59, 2003-10). RESULTS: Type-concordance of cervicogenital and oral infections in women was found to vary widely by age. Prevalence of oral infections with type-concordant antibodies was low but varied by sex: 0.2 % (95 % CI 0.0-0.8) for women vs 0.8 % (95 % CI 0.4-1.3) for men. Vaccination was associated with a reduced risk of cervicogenital infection for vaccine genotypes among ages 14-17 (0.2 (95 % CI 0.1-0.8)) and 18-24 (0.2 (95 % CI 0.1-0.3). Seroprevalence trends in women showed a dramatic increase for recent birth cohorts, likely due to vaccination. By contrast, trends for men remained relatively constant. Age-specific cervicogenital prevalence showed a consistent peak in the late teens and twenties. Relative cervicogenital prevalence has largely been decreasing since the 1940-50 birth cohort. CONCLUSIONS: There are complex patterns in HPV prevalence trends and type-concordance across infection sites and serum antibodies. A multisite sampling scheme is needed to better understand the epidemiology and natural history of HPV.

Lack of association between serum 25-hydroxyvitamin D levels and cervical human papillomavirus infection in systemic lupus erythematosus.

Our objective was to evaluate whether vitamin D deficiency is associated with cervical human papilloma virus (HPV) infection in women with SLE. This is a cross-sectional study of 67 women with SLE. A structured questionnaire was administered to ascertain the possible risk factors associated with cervical HPV infection. A gynaecological evaluation and cervical cytology screening were made. HPV detection and genotyping was made by PCR and linear array assay. Serum 25 hydroxyvitamin D levels were quantified by chemiluminescence immunoassay. Mean age and disease duration were 44.8 ± 10.6 and 42.5 ± 11.8 years, respectively. Demographic characteristics were similar in patients with and without deficiency (<20 ng/ml and ≥20 ng/ml). There were 28.4% of women with cervical HPV infection and 68.4% had high-risk HPV infections. Patients with 25 hydroxyvitamin D levels <20 ng/ml had a higher prevalence of cervical HPV infection than those with levels ≥20 ng/ml (30.7% vs. 25.8%; p = 0.72). We found no significant difference when high-risk HPV infection was evaluated (36.8% vs. 31.5%; p = 0.73). In conclusion, women with SLE have a high prevalence of vitamin D deficiency and cervical HPV infection. However, we found no association between vitamin D deficiency and cervical HPV.

Interferon gamma, interleukin 8 and interleukin 10 in serum of patients with the cervical infection and symptoms of the imminent preterm delivery.

INTRODUCTION: Preterm delivery (PTD), defined as a delivery between 24th and 37th completed week, increases the risk of neonatal morbidity and mortality. There is a growing body of evidence that the intrauterine infection as well as cervicovaginal bacterial infections and Chlamydia infections are possible causes of preterm delivery. Host response to cervicovaginal and/or intrauterine infections is coupled with a release of various inflammatory mediators, many of which are cytokines. OBJECTIVE: The aim of the study was to find out if cervical infection influenced the serum levels of interferon-gamma (IFN-gamma), interleukin 8 (IL-8) and interleukin 10 (IL-10) in patients with the clinical symptoms of the imminent preterm delivery. METHODS: A total of 128 pregnant women (from 24 to 30 weeks of gestation) with the clinical symptoms of the imminent preterm delivery were divided in: study group--85 patients with the cervical infection, and control group--43 patients without the cervical infection. The level of cytokines in the serum was measured with commercial ELISA tests. RESULTS: No significant difference could be found in serum levels of IFN-gamma (p = 0.632), IL-8 (p = 0.712) and IL-10 (p = 0.676) between these two investigated groups. CONCLUSION: The results of our study suggest that there is no significant difference in serum IFN-gamma, IL-8 and IL-10 concentrations between pregnant women with the symptoms of the imminent preterm delivery who had and had no cervical infection.

The prevalences of Neisseria gonorrhoeae and Chlamydia trachomatis infections among female sex workers in China.

BACKGROUND: Sexually transmitted infections (STIs) have become a major public health problem among female sex workers (FSWs) in China. There have been many studies on prevalences of HIV and syphilis but the data about Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) infections are limited in this population in China. METHODS: A cross-sectional study was performed among FSWs recruited from different types of venues in 8 cities in China. An interview with questionnaire was conducted, followed by collection of a blood and cervical swab specimens for tests of HIV, syphilis, NG and CT infections. RESULTS: A total of 3,099 FSWs were included in the study. The overall prevalence rates of HIV, syphilis, NG and CT were 0.26%, 6.45%, 5.91% and 17.30%, respectively. Being a FSW from low-tier venue (adjusted odds ratios [AOR]=1.39) had higher risk and being age of ≥ 21 years (AOR=0.60 for 21-25 years; AOR=0.29 for 26-30 years; AOR=0.35 for 31 years or above) had lower risk for CT infection; and having CT infection was significantly associated with NG infection. CONCLUSIONS: The high STI prevalence rates found among FSWs, especially among FSWs in low-tier sex work venues, suggest that the comprehensive prevention and control programs including not only behavioral interventions but also screening and medical care are needed to meet the needs of this population.

Development of a pigtail macaque model of sexually transmitted infection/HIV coinfection using Chlamydia trachomatis, Trichomonas vaginalis, and SHIV(SF162P3).

BACKGROUND: Sexually transmitted infections (STIs) are associated with an increased risk of HIV infection. To model the interaction between STIs and HIV infection, we evaluated the capacity of the pigtail macaque model to sustain triple infection with Trichomonas vaginalis, Chlamydia trachomatis, and SHIV(SF162P3). METHODS: Seven SHIV(SF162P3) -infected pigtail macaques were inoculated with T. vaginalis only (n = 2), C. trachomatis only (n = 1), both T. vaginalis and C. trachomatis (n = 2), or control media (no STI; n = 2). Infections were confirmed by culture and/or nucleic acid testing. Genital mucosa was visualized by colposcopy. RESULTS: Characteristic gynecologic signs were observed for both STIs, but not in control animals. Manifestations were most prominent at days 7-10 post-infection. STIs persisted between 4 and 6 weeks and were cleared with antibiotics. CONCLUSIONS: These pilot studies demonstrate the first successful STI-SHIV triple infection of pigtail macaques, with clinical presentation of genital STI symptoms similar to those observed in humans.

Lack of HPV 16 and 18 detection in serum of colposcopy clinic patients.

BACKGROUND: Persistent infection with high-risk human papillomavirus (HPV) types is necessary for the development of high-grade cervical dysplasia and cervical carcinoma. The presence of HPV DNA in the blood of cervical cancer patients has been reported; however, whether HPV DNA is detectable in the blood of patients with pre-invasive cervical disease is unclear. OBJECTIVES: The objectives of this study were to determine if HPV 16 and HPV 18 DNA could be detected in the serum of colposcopy clinic patients, and if serum HPV detection was associated with grade of cervical disease and HPV cofactors. STUDY DESIGN: Samples were selected from a biorepository collected from non-pregnant, HIV-negative women ages 18-69 attending colposcopy clinics at two urban public hospitals. Cervical disease status was based on review of colposcopy, biopsy and cytology findings. Serum HPV DNA detection was conducted using a novel PCR and mass spectroscopy-based assay. RESULTS: Of the 116 adequate serum samples, all (100%) were negative for HPV 16 and HPV 18. Over half (51.7%) of participants had cervical HPV 16 and/or HPV 18 infection. Nearly one-third (31.1%) had high grade, 10.3% had low grade, and 50.9% had no cervical disease. Nearly one-third (28.5%) had ever regularly smoked cigarettes, 70.7% had early onset of sexual intercourse, and 75% had ever used oral contraceptives. CONCLUSIONS: In this colposcopy clinic population with a range of clinical characteristics and established HPV cofactors, HPV DNA was undetectable in their serum. Our findings suggest that serum HPV DNA detection is not a cervical cancer screening tool.

An efficient conservative treatment modality for cervical pregnancy: angiographic uterine artery embolization followed by immediate curettage.

OBJECTIVE: We sought to evaluate a conservative treatment modality, angiographic uterine artery embolization (UAE) followed by immediate curettage, in the treatment of cervical pregnancy. STUDY DESIGN: Sixteen patients with cervical pregnancy were first treated by UAE to control or prevent vaginal bleeding. Curettage of cervical canal was performed immediately after UAE to remove gestational tissue from the cervix. Clinical outcome assessments include vaginal bleeding, serum ß-human chorionic gonadotropin level, cervical mass, menstruation, fertility, and hospitalization time. RESULTS: Fifteen patients were successfully treated by UAE followed by immediate curettage. One patient at very early gestational age underwent UAE only. Quick regression of serum human chorionic gonadotropin level and cervical mass, fertility preservation, and a short hospital stay were observed. CONCLUSION: UAE followed by immediate curettage is an efficient conservative treatment for cervical pregnancy. This procedure may become a useful alternative to other conservative approaches.

Plasma micronutrients and the acquisition and clearance of anal human papillomavirus infection: the Hawaii HPV cohort study.

Anal human papillomavirus (HPV) infection is common among women and the cause of most anal malignancies. The incidence of anal cancer has been increasing among U.S. women, yet few cofactors for the natural history of anal HPV infection have been identified. We examined the hypothesis that plasma carotenoid, retinol, and tocopherol concentrations are associated with the acquisition and clearance of anal HPV infection in a cohort of 279 Hawaiian residents followed at 4-month intervals for a mean duration of 16 months. At each visit, interviews were conducted and biological specimens were obtained, including anal cell specimens for HPV DNA detection and genotyping, and a fasting blood sample to measure 27 micronutrients. Cohort participants acquired 189 anal HPV infections, 113 of which cleared during the study period. The most frequently acquired HPV genotypes were HPV-52, -53, -84, and -16. Women in the highest quartile of trans-zeaxanthin, trans -anhydro-lutein, and trans-, cis-, and total ß-carotene had significant 43% to 50% reduction in the risk of acquisition of any HPV infection compared with women in the lowest quartile. Few associations were observed between micronutrient levels and clearance of transient (≤ 150 days) anal HPV infections. However, clearance of persistent (> 150 days) infections was associated with higher levels of ß-tocopherol + γ-tocopherol and lower levels of carotenoids and retinol. Our findings suggest that several carotenoids can reduce the risk and clearance of anal HPV infections that contribute to anal cancer.

Giant endocervical polyp mimicking cervical malignancy: primary excision and hysteroscopic resection.

Giant cervical polyps are characterized by an unusually large size and appear clinically as malignant. A 35-year-old woman had increased vaginal discharge and lower abdominal discomfort. At examination, a fist-sized, hard, consistent mass was found in the vagina. Pelvic magnetic resonance imaging revealed a 12.6 x 8-cm solid tumor with internal papillary growth within the entire vaginal cavity. The tumor base was suspected to have originated from the endocervix by a connecting stalk. Primary excision of the tumor was performed via the vagina, and the remnant tissue was completely removed at hysteroscopic resection. The final histopathologic findings confirmed a benign giant cervical polyp.

Six-month natural history of oral versus cervical human papillomavirus infection.

Human papillomavirus (HPV) infection is etiologically associated with a subset of oral cancers, and yet, the natural history of oral HPV infection remains unexplored. The feasibility of studying oral HPV natural history was evaluated by collecting oral rinse samples on 2 occasions at a 6-month interval from 136 HIV-positive and 63 HIV-negative participants. Cervical vaginal lavage samples were concurrently collected for comparison. HPV genomic DNA was detected in oral and cervical samples by consensus primer PCR and type-specified for 37 HPV types. The six-month cumulative prevalence of oral HPV infection was significantly less than for cervical infection (p < 0.0001). HIV-positive women were more likely than HIV-negative women to have an oral (33 vs. 15%, p = 0.016) or cervical (78 vs. 51%, p < 0.001) infection detected. Oral HPV infections detected at baseline were as likely as cervical infections to persist to 6 months among HIV-negative (60% vs. 51%, p = 0.70) and HIV-positive (55% vs. 63%, p = 0.27) women. Factors that independently elevated odds for oral HPV persistence differed from cervical infection and included current smoking (OR = 8, 95% CI = 1.3-53), age above 44 years (OR = 20, 95% CI = 4.1-83), CD4 < 500 (OR = 6, 95% CI = 1.1-26), use of HAART therapy (OR = 12, 95% CI = 1.0-156), and time on HAART therapy (trend p = 0.04). The rate of oral HPV infections newly detected at follow-up was significantly lower than cervical infection among HIV-positive (p < 0.001) and HIV-negative women (p < 0.001). Our study not only demonstrates that it is feasible to study the natural history of oral HPV infection with oral rinse sampling, but also indicates that oral and cervical HPV natural history may differ.

Correlates of the spread of human papillomavirus infection.

Knowledge of the correlates of human papillomavirus (HPV) seropositivity is of interest for planning of preventive measures and for evaluation of possible confounding in epidemiological studies. The epidemiological determinants for seropositivity for oncogenic and benign HPV types were assessed using a serosurvey of 275 healthy Swedish women, stratified by age and lifetime number of sexual partners. Seroprevalences were compared with 17 behavioral variables obtained by interview and 3 laboratory-diagnosed microbiological exposures. In univariate analysis, history of gonorrhea and condylomatosis, human herpesvirus type 8 and herpes simplex virus 2 seropositivities, lifetime number of sexual partners, and current partner's lifetime number of sexual partners were associated with oncogenic HPV seropositivity. Noteworthy lack of correlations included smoking habits and oral contraceptive use. In multivariate analysis, only the number of lifetime sexual partners [odds ratio (OR), 8.7; 95% confidence interval (CI), 3.3-22.6] and seropositivity for benign HPV types remained significant (OR, 2.9; 95% CI, 1.6-5.3). Seropositivity for benign HPV was primarily associated with condyloma history (OR, 3.6; 95% CI, 1.2-10.8) and seropositivity for oncogenic HPV (OR, 2.9; 95% CI, 1.6-5.2). An association with sexual history lost significance in the multivariate model. In conclusion, lifetime number of sexual partners is the major determinant of acquisition of oncogenic HPV. By contrast, benign HPV infection associates more strongly with condyloma history than with sexual history per se.

Low correlation of serology with detection of Chlamydia trachomatis by ligase chain reaction and antigen EIA.

The aim of the present study was to evaluate the diagnostic accuracy of serology by using new assays for the detection of genus and species-specific IgG, IgM, IgA and secretory IgA antibody in female sex workers. Cervical swabs and first void urine (FVU) from 314 female sex workers were submitted to nucleic acid amplification by ligase chain reaction (LCx, Abbott). Concomittantly, blood samples were tested for the presence of IgG, IgM and IgA antibodies using a genus-specific assay (rELISA, Medac) and species-specific test (SeroCT, Orgenics). Chlamydia trachomatis infection was detected in a total of 30 (9.6%) female sex workers by LCR. With rELISA, seroprevalences for IgG, IgM, and IgA antibody to Chlamydia were 88.9%, 19.1% and 62.7%, respectively. IgG and IgA antibody prevalences against C. trachomatis (SeroCT) were 65.0% and 23.9%, respectively. In comparison to the positive LCR results obtained from cervical swab and/or FVU, the sensitivity of rELISA for Chlamydia IgG, IgA and IgM detection was 93.3%, 83.3% and 16.7%, respectively. With SeroCT, the sensitivity for C. trachomatis-specific IgG and IgA detection was 86.7% and 33.3%, respectively. The specificities of both serologic tests in comparison to LCR were very low. In conclusion, the correlation of serology with active C. trachomatis infection of the lower genital tract is very low. According to our results, serologic testing for Chlamydia can exclude active infection of the lower genital tract with a high reliability (> or = 95%). However, detection of C. trachomatis can only be reliably achieved by nucleic acid amplification assays.

Serum levels of macrophage colony-stimulating factor-1 in cervical human papillomavirus infection and intraepithelial neoplasia.

OBJECTIVE: Our goal was determine the correlation between serum colony stimulating factor-1 levels, cervical human papillomavirus infection, and dysplasia. STUDY DESIGN: Serum samples were obtained from control subjects from the United States and from a group of Panamanian women. Members of the latter group fell into 3 categories: those who serve as Panamanian control subjects and who test negative for human papillomavirus (n = 10); those who are high risk by history and test positive for human papillomavirus types 16/18 and 30s (n = 10); and those with the same high-risk history with biopsy-proven cervical intraepithelial neoplasia (n = 8). Serum colony-stimulating factor-1 levels were determined using enzyme-linked immunosorbent assay. Data were analyzed with the Student-Newman-Keuls and t tests. RESULTS: Mean serum colony-stimulating factor-1 levels of patients with a positive test result for human papillomavirus (1166 +/- 949 pg/mL) and cervical intraepithelial neoplasia (1295 +/- 314 pg/mL) were higher than those of control subjects from the United States (584 +/- 237 pg/mL) and those of Panamanian control subjects (520 +/- 229 pg/mL). Statistical analysis revealed the concentration of colony-stimulating factor in patients with positive test results for human papillomavirus or cervical intraepithelial neoplasia were significantly higher than in control groups. In addition, combining patients with human papillomavirus with those who have cervical intraepithelial neoplasia results in a group that has significantly higher colony-stimulating factor levels compared with control subjects. CONCLUSIONS: Both high-grade cervical dysplasia and high-risk human papillomavirus infection are associated with higher mean serum colony-stimulating factor levels, suggesting a possible role for colony-stimulating factor-1 in cervical neoplasia. Further studies are needed to understand the mechanism of colony- stimulating factor activation in human papillomavirus infection. This may assist in designing therapeutic approaches for the management of this disease.

Concentrations of carotenoids, tocopherols, and retinol in paired plasma and cervical tissue of patients with cervical cancer, precancer, and noncancerous diseases.

Paired blood (collected after an overnight fast) and cervical tissue (cancerous, precancerous, and noncancerous) samples were obtained from 87 patients (age, 21-86 years) who had a hysterectomy or biopsy due to cervical cancer, precancer (cervical intraepithelial neoplasia I, II, and III), or noncancerous diseases. The samples were analyzed using high-performance liquid chromatography for 10 micronutrients (lutein, zeaxanthin, beta-cryptoxanthin, lycopene, alpha-carotene, beta-carotene, cis-beta-carotene, alpha-tocopherol, gamma-tocopherol, and retinol). The results indicated that: (a) among the three patient groups, the mean plasma concentrations of all micronutrients except gamma-tocopherol were lowest in the cancer patients; however, the mean tissue concentrations of the two tocopherols and certain carotenoids were highest in the cancerous tissue; and (b) among the 10 micronutrients, only the concentrations of beta-carotene and cis-beta-carotene were lower in both the plasma and tissue of cancer and precancer patients than in those of noncancer controls. These results suggest that: (a) not all of the micronutrient concentrations in plasma reflect the micronutrient concentrations in cervical tissue; thus, in some cases, it may be necessary to measure the tissue micronutrient concentrations to define the role of the micronutrients in cervical carcinogenesis; and (b) maintaining an adequate plasma and tissue concentration of beta-carotene may be necessary for the prevention of cervical cancer and precancer.

Detection of serologic neutralizing antibodies against HPV-11 in patients with condyloma acuminata and cervical dysplasia using an in vitro assay.

This study was designed to investigate if neutralizing antibodies against HPV-11 are detectable in the serum of patients with condyloma acuminata (CA) or cervical intraepithelial neoplasia (CIN) using an in vitro infectivity assay for HPV-11. Purified HPV-11 virions were extracted from xenografted condyloma tissues implanted into athymic mice and used to infect cultured neonatal human foreskin keratinocytes (HFK) and an immortalized adult skin cell line (HaCaT). The presence of HPV-11-specific E1--E4 mRNA as detected by reverse transcriptase-polymerase chain reaction was indicative of early infection. Sera previously characterized for reactivity to HPV-11 and HPV-11 VLP (virus-like particles) by ELISA were tested for the ability to prevent HPV-11 in vitro infectivity. Neutralizing antibodies against HPV-11 were demonstrated when monoclonal antibodies or patient serum preincubated with HPV-11 virions prevented the infection of either of the two cell cultures, as shown by the absence of the E1--E4 mRNA transcript. Eleven (of 20) patients with CA were strongly ELISA reactive against HPV-11 virus-like particles. Five of these 11 patients also had detectable levels of neutralizing antibodies in their serum. It was also demonstrated that the neutralizing properties of the serum were titratable by endpoint dilution. None of 15 patients with CIN had detectable neutralizing antibodies against HPV-11. Neutralizing antibodies against HPV-11 can be detected in some patients with CA and the neutralizing effects of the patient sera can be titrated by endpoint dilution. The in vitro assay for the detection of neutralizing antibodies against HPV-11 may have utility for investigating the natural history of HPV infection and resolution, as well as assessing the efficacy of any putative HPV vaccine.

Design and methods of a population-based natural history study of cervical neoplasia in a rural province of Costa Rica: the Guanacaste Project.

This paper reports on the enrollment phase of a population-based natural history study of cervical neoplasia in Guanacaste, a rural province of Costa Rica with consistently high rates of invasive cervical cancer. The main goals of the study are to investigate the role of human papillomavirus (HPV) infection and its co-factors in the etiology of high-grade cervical neoplasia, and to evaluate new cervical cancer screening technologies. To begin, a random sample of censal segments was selected and enumeration of all resident women 18 years of age and over was conducted with the aid of outreach workers of the Costa Rican Ministry of Health. Of the 10738 women who were eligible to participate, 10049 (93.6%) were interviewed after giving written informed consent. After the interview on cervical cancer risk factors was administered, a pelvic examination was performed on those women who reported previous sexual activity. The pelvic examination included a vaginal pH determination and collection of cervical cells for cytologic diagnosis using three different techniques. Additional cervical cells were collected for determination of the presence and amount of DNA from 16 different types of HPV, and two photographic images of the cervix were taken and interpreted offsite by an expert colposcopist. Finally, blood samples were collected for immunologic and micronutrient assays. Women with any abnormal cytologic diagnosis or a positive Cervigram, as well as a sample of the whole group, were referred for colposcopy, and biopsies were taken when lesions were observed. The enrollment screening will serve as the basis for a prevalent case-control study, and the members of the cohort free from serious disease will be followed actively, at intervals of no more than a year, to study the natural history of HPV infection and the origins of high-grade squamous intraepithelial lesions (HSIL). Details of the field operation are outlined, with particular reference to the realization of this kind of study in developing countries. Descriptive data on the prevalence of disease and exposure to various risk factors are also presented.

Prevalence of transformation zone Chlamydia trachomatis DNA and serum antibodies in Tanzanian gynaecological in-patients.

Chlamydia trachomatis DNA was detected in cervical transformation zone swabs of gynaecological in-patients from Tanzania by two different polymerase chain reactions (PCR), one targetting the endogenous Chlamydia trachomatis plasmid (pCTT1) and the other a chlamydia genus specific rRNA gene. In only 7/131 (5.3%) cervical samples specific amplification products were obtained, in 6 cases with both PCRs, and in one with the plasmid-PCR alone. A 255 nt sequence was determined from the two plasmid-PCR fragments and revealed only one mismatch against the prototype sequence. Antibodies against genus specific chlamydia antigens were detectable by indirect immunofluorescence with titres > or = 1:256 in 29.0% (38/131) of all patients and in 50.0% (11/22) of patients with pelvic inflammatory disease (P = 0.17). No statistically significant association of either chlamydia antibodies or chlamydial DNA with any clinical condition was observable.