Mechanical dilatation of the stenosed cervix under local anesthesia: A prospective case series.

AIM: Cervical stenosis is traditionally managed by mechanical dilatation under general anesthesia (GA). We aimed to assess the safety, effectiveness, and patient acceptability of dilatation in the outpatient setting under local anesthesia (LA). METHODS: Data were collected prospectively from all patients attending the outpatient department with cervical stenosis from March 20, 2015 to September 23, 2020. Mechanical dilatation of the cervix was performed using Hegar dilators under LA. Subsequent colposcopic assessment, cytology, histology, and management were recorded. RESULTS: One hundred forty-nine cases were referred for cervical dilatation, 63 (43%) of which had complete stenosis. One hundred eighteen (79%) patients had previously undergone cervical procedures. Successful dilatation under LA was achieved in 119 (83%) patients; 5 (3%) declined (requesting GA), 6 (4%) did not tolerate speculum examination, and 19 (13%) had unsuccessful procedures. The median Hegar size used was 8 mm. Dilatation under LA was acceptable in 93% attempted procedures. Thirteen episodes of restenosis were recorded with no major adverse events. Younger age (p = 0.045) and severe (compared to complete) stenosis (p < 0.0001) were associated with procedure success, with improved results over time (p = 0.003). Successful dilatation permitted cervical assessment; eight patients required cervical excisions, two underwent hysterectomies, with one confirmed case of adenocarcinoma. CONCLUSION: Rigid cervical dilatation in the outpatient setting provides effective, instantaneous treatment for women who have failed cytological or colposcopic assessment. For the vast majority of women, the procedure was well tolerated and preferred to using GA. However, given that 1 in 10 women experienced restenosis, patients should be counseled about the possibility of requiring further management.

Evidence to Support Change of Clinical Pathway Following Colposcopy Treatment for Cervical Intraepithelial Neoplasia in Canada.

OBJECTIVES: Human papillomavirus (HPV) testing can be incorporated into the post-treatment pathway of cervical intraepithelial neoplasia (CIN) to confirm disease-free status. To inform a post-treatment strategy based on risk of recurrence, we modelled disease and economic outcomes. METHODS: The current Alberta, Canada, post-treatment care pathway-cytology testing with colposcopy assessment-was compared with 6 other scenarios incorporating cytology, HPV testing, or both tests at different time points in a modelling study based on a microsimulation program. Input parameter values for the screening participation, screening age groups, and follow-up options and test compliance for HPV, cytology, and colposcopy were varied, based on Alberta cervical cancer screening program data. Health outcomes over the short- and long-term were projected, which incorporated the increasing population-level coverage of HPV vaccination. Lifetime incremental cost-effectiveness ratios (ICERs) were used to evaluate economic outcomes and descriptive statistics compared with numbers of tests, visits, and procedures as well as changes in incidence and mortality rates between the scenarios. RESULTS: At 5 years after implementation of the "HPV testing alone at 6 and 18 months" post-treatment pathway, the number of colposcopies dropped by 36% and the number of pre-cancer treatments, by 6%. Lifetime ICERs were CAD $6170 versus $248,495 per quality-adjusted life-year compared with the status quo pathway. Cervical cancer incidence and mortality rates decreased significantly and similarly in all scenarios. CONCLUSION: Strategies that involve HPV testing in CIN post-treatment follow-up care are expected to be more cost effective with improved clinical outcomes than traditional cytology and colposcopy-based follow-up.

Vaginal drug delivery approaches for localized management of cervical cancer.

Cervical cancer or cervical intraepithelial neoplasia (CIN) remain a major public health problem among women globally. Traditional methods such as surgery are often associated with possible complications which may impact future pregnancies and childbirth especially for young female patients. Vagina with a high contact surface is a suitable route for the local and systemic delivery of drugs but its abundant mucus in continuous exchange presents a barrier for the popularization of conventional vaginal formulations including suppositories, gel, patch, creams and so on. So the development of new pharmaceutical forms based on nanotechnology became appealing owing to its several advantages such as mucosa penetration, bioadhesion, controlled drug release, and decreased adverse effects. This review provided an overview of the development of topical treatment of cervical cancer or CIN through vaginal drug delivery ranging from conventional vaginal formulations to new nanocarriers to the newly developed phototherapy and gene therapy, analyzing the problems faced by current methods used, and advising the developing trend in future. The methods of establishing preclinical animal model are also discussed.

Therapeutic Applications of Human and Bovine Colostrum in the Treatment of Gastrointestinal Diseases and Distinctive Cancer Types: The Current Evidence.

The incidence of gastrointestinal disorders (GID) and cancers is escalating all over the world. Limited consumption of colostrum by newborns not only weakens the immune system but also predisposes infants to microbial infections. Colostrum is nature's perfect food, sometimes referred to as the 'elixir of life'. Breast-fed infants have a lower incidence of GI tract infections than infants fed formula or cow's milk. As per WHO statistics, cancer is the most prevalent disease globally and causes 9.6 million deaths worldwide. The current strategies for treating cancer include chemotherapy, radiation, and surgery. However, chemotherapy and radiation exposure are usually associated with serious long-term side effects and deterioration in the quality of life (QOL) of patients. Furthermore, the hospitalization and medication costs for treating cancers are exorbitant and impose high economic burden on healthcare systems. People are desperately looking for cost-effective and affordable alternative therapies for treating GID and cancers. Therefore, there is an urgent need for clinically evaluating the anticancer compounds isolated from plants and animals. Such therapies would not only be economical and have fewer side effects, but also help to improve the QOL of cancer patients. Recently, bovine colostrum (BC) has caught the attention of many investigators to explore its anticancer potential in humans. BC impregnated dressings are highly effective in treating chronic wounds and diabetic foot ulcer. BC is rich in lactoferrin, a glycoprotein with strong antioxidant, anti-inflammatory, anti-cancer, and anti-microbial properties. Intravaginal application of BC tablets is effective in causing the regression of low-grade cervical intraepithelial neoplasia. The underlying mechanisms of BC at cellular, genetic, and molecular levels remain to be ascertained. Oral BC supplement is well-tolerated, but some people may experience problems such as flatulence and nausea. Well-designed, randomized, placebo-controlled, clinical trials are needed to access the therapeutic potential, long-term safety, and optimal doses of BC products. This review is aimed to highlight the anticancer potential of BC and its components, and the therapeutic applications of BC supplements in treating gastrointestinal diseases in children and adults. We also discuss the health promotion benefits and therapeutic potential of BC nutraceuticals in reducing the incidence of non-communicable diseases.

Topical therapies for the treatment of cervical intraepithelial neoplasia (CIN) 2-3: A narrative review.

Current management of Cervical Intraepithelial Neoplasia (CIN), caused by high-risk human papillomavirus (hr-HPV), is based on surveillance and surgical therapy. Procedures carry potential risks such as preterm birth, and access remains limited throughout the world. However, there are no medical therapies recommended to promote the clearance of hr-HPV infection or CIN. Ultimately, even if less efficacious than excision procedures, medical therapies have the potential to decrease cervical cancer by eliminating barriers to treatment, such as access to treatment, or serving as an adjunct to surgical treatment in both high- and low-resource settings. This review describes current research on topical therapies with the potential for self-application for the treatment of HPV or CIN. Therapies included are immune-modulators, anti-proliferative medications, antivirals, hormones, and herbal/alternative therapies. Randomized trials of immune-modulating (imiquimod), anti-proliferative (5-fluorouracil), and anti-viral (cidofovir) therapies have had the most promising results. However, no option has sufficient clinical trial evidence to be recommended as treatment for CIN 2-3 and surgery remains the standard of care. The research described in this review serves as a guide for the development of future trials in the burgeoning arena of topical therapies for CIN 2-3.

LLETZ make it simple: Anxiety, pain and treatment outcomes with outpatient large loop excision of the transformation zone under local anaesthesia.

BACKGROUND: Large loop excision of the transformation zone (LLETZ) is the preferred treatment for cervical intraepithelial neoplasia due to its effectiveness and ability to be performed in an outpatient setting under local anaesthesia (LA). Although current guidelines recommend that most LLETZ can be performed under LA, there is paucity in clinical data of patients' perspectives of outpatient LLETZ. AIM: Determining patient acceptability of outpatient LLETZ through assessment of anxiety and pain scores, and comparing treatment outcomes with current standards in terms of margins status, negative histology, short-term morbidity rates and follow-up attendance. MATERIALS AND METHODS: This study was conducted at a tertiary hospital over two years (2014-2016). Patients undergoing outpatient LLETZ completed a three-part questionnaire (before, immediately after and 4-6 weeks post-procedure). RESULTS: One hundred and five patients underwent outpatient LLETZ. Mean pain score was 2 (range 0-8). Pre-procedure anxiety was common but most resolved post-procedure. Women who did not have a prior LLETZ discussion were more likely to report moderate-severe anxiety levels pre-procedure, compared with women who did (odds ratio 3.00, 95% CI 1.11-8.09, P = 0.030). There were no differences found in pain scores when comparing pre-procedure anxiety levels, prior discussion of LLETZ or mode of anaesthesia. Specimen margins were involved in 42.9%. No association was found between positive cervical margin status and age, pre-procedure anxiety or post-procedure pain scores. Most patients were satisfied and attended follow-up appointments. CONCLUSION: Large loop excision of the transformation zone under LA is a well-tolerated procedure with high satisfaction and follow-up rates. Clinicians need to initiate early discussions regarding treatment to minimise procedure-related anxiety.

Clinical value of P16 and Ki-67 expressions in cervical biopsy for predicting early cervical cancer in patients with high-risk HPV infection / 中国基层医药

Objective@#To explore the positive expressions of P16 and Ki-67 proteins in cervical biopsy lesions of patients with high-risk HPV infection and abnormal detection of liquid-based thin-layer cytology test(TCT), and the clinical value in predicting occurrence of early cervical cancer.@*Methods@#A total of 120 patients with high-risk HPV infection(16 and 18 subtypes positive) and abnormal TCT in the Traditional Chinese Medicine Hospital of Linhai from January 2016 to July 2017 were enrolled in the study.The colposcopy was used to get cervical biopsy lesions for pathological diagnosis, immunohistochemical staining was used to detect P16 and Ki-67 proteins.@*Results@#There were up to 66 patients with HPV-16 positive, 34 cases with HPV-18 positive, other 20 cases with 16 and 18 positive; 6 cases of atypical squamous epithelial cells(ASC), 46 cases of low-grade squamous intraepithelial lesions (LSIL), 60 cases of high-grade SIL(HSIL), other 8 cases of cervical squamous cell carcinoma(SCC) were diagnosed by TCT; 5 cases of inflammation, 105 cases of CIN and 10 cases of SCC by pathologically diagnosis.The positive rates of P16 and Ki-67 proteins were gradually increased in patients with inflammation, CIN and SCC[0(0/5), 36.2%(38/105), 70.0%(7/10), χ2=4.382, P=0.036; 0(0/5), 40.0%(42/105), 80.0%(8/10), χ2=5.945, P=0.015]. The patients with CIN were followed up for 21~36 months, median time 29.5 months.Twenty-six patients progressed to SCC, at the end of follow-up, the positive rates of P16 and Ki-67 proteins in patients with SCC were significantly higher than those in the CIN patients without progress[61.5%(16/26) vs.39.2%(31/79), χ2=3.934, P=0.047; 69.2%(18/26) vs.41.8%(33/79), χ2=5.905, P=0.015].@*Conclusion@#The positive expression rates of P16 and Ki-67 proteins in cervical biopsy tissues are significantly higher in patients with high-risk HPV infection and abnormal TCT, which in patients with pathologically diagnosis of SCC are higher than CIN patients, the same results in CIN patients with SCC progression than non-progressing patients, suggesting that P16 and Ki-67 proteins are of great value in predicting occurrence of early cervical cancer.

Intravaginal Application of Topical Black Salve for High-Grade Cervical Intraepithelial Neoplasia.

Background: Black salve, or sanguinarine, is a topical escharotic agent that has been used by patients for homeopathic ablation of epithelial dysplasia, including cervical intraepithelial neoplasia. Case Report: A 33-year-old female presented to the obstetric and gynecologic clinic for management of a missed abortion. At the time of presentation, she admitted to the use of topical black salve for treatment of cervical intraepithelial neoplasia 2 years prior. Speculum examination revealed a stenotic cervix that appeared flush against the vaginal cuff. Hysteroscopy performed 4 months later after the patient developed new oligomenorrhea revealed significant vaginal scarring with formation of a blind pouch that concealed the true cervix. Conclusion: Health care providers should be aware of homeopathic remedies trialed by patients on their own or as an alternative to recommended treatment. Such self-treatment may cause significant patient harm, such as scarring or deformity.

The Relationship between the Serum Level of Selenium and Cervical Intraepithelial Neoplasia: A Comparative Study in a Population of Nigerian Women

Objective: To determine the relationship between the serum level of selenium and cervical intraepithelial neoplasia (CIN). Methods: A case controlled study that compared the serum level of selenium in 45 women with CIN (cases) to 45 women (age matched controls) with normal cervical cytology. Socio-demographic data and information on known risk factors for cervical cancer among the sample was compared between both groups using inferential statistics. Results: There was no significant difference in the mean selenium values between the cases and controls [p- 0.076, 95% CI (-15.08 ­ 0.76)]. However, subgroup analysis showed a statistically significant difference between patients with normal cervical cytology, CIN I, II and III (p= 0.021). In addition, there was also significant difference in the selenium level between women with normal cervical cytology and CIN III (p value = 0.016) with a significant inverse linear trend (p= 0.025). Conclusion: With increasing severity of CIN, a significant reduction in the level of selenium in serum was observed. This reducing value of serum selenium, a surrogate marker for increased oxidative stress, may be important factor for the development of persistent HPV infection and in particular high grade CIN III lesions. This observation requires further research.

Management and treatment of cervical intraepithelial neoplasia in the Netherlands after referral for colposcopy.

INTRODUCTION: The aim of this study was to describe trends in the diagnosis and treatment of women referred from the national screening program with cervical intraepithelial neoplasia (CIN) in the Netherlands, and to compare these trends with national guidelines and identify potential areas for improvement for the new primary high-risk HPV screening program. MATERIAL AND METHODS: We conducted a population-based cohort study using data from the Dutch pathology archive. Women aged 29-63 years who took part in the Dutch cervical screening program between 1 January 2005 and 31 December 2014 were selected. Three referral groups were identified: direct referrals and those referred after either one (first indirect referrals) or two (second indirect referrals) repeat cytology tests, totaling 85 239 referrals for colposcopy. The most invasive management technique and the most severe diagnosis of each screening episode was identified. Rates of management techniques were calculated separately by referral type, highest CIN diagnosis and age group. RESULTS: In all, 85.1% of CIN 3 lesions were treated with excision (either large excision or hysterectomy) and 26.4% of CIN 1 lesions were treated with large excision. Rates of overtreatment (CIN 1 or less) in see-and-treat management were higher for indirect referrals than for direct referrals and increased with age. Large excision rates increased with CIN diagnosis severity. CONCLUSIONS: Despite guideline recommendations not to treat, CIN 1 lesions were treated in just over 25% of cases and approximately 15% of CIN 3 lesions were possibly undertreated. Given the expected increase in CIN detection in the new primary high-risk HPV screening program, reduction in CIN 1 treatment and CIN 2 treatment in younger women is needed to avoid an increase in potential harm.

Long-Term Vitamin D Supplementation and the Effects on Recurrence and Metabolic Status of Cervical Intraepithelial Neoplasia Grade 2 or 3: A Randomized, Double-Blind, Placebo-Controlled Trial.

OBJECTIVE: This study was conducted to evaluate the effects of vitamin D supplementation on the recurrence and metabolic status of patients with cervical intraepithelial neoplasia grade 2 or 3 (CIN2/3). METHODS: This randomized, double-blind, placebo-controlled trial was carried out among 58 women diagnosed with CIN2/3. Participants were randomly assigned into 2 groups to receive either 50,000 IU vitamin D3 (n = 29) or placebo (n = 29) every 2 weeks for 6 months. RESULTS: The recurrence rate of CIN1/2/3 was 18.5 and 48.1% in the vitamin D and placebo groups respectively (p = 0.02). When we excluded CIN1, the recurrence rate of CIN2/3 became nonsignificant. Vitamin D supplementation significantly decreased fasting plasma glucose (-7.8 ± 9.2 vs. -1.1 ± 8.6 mg/dL, p = 0.006) and insulin levels (-3.2 ± 4.8 vs. -0.9 ± 3.4 µIU/mL, p = 0.03), and significantly increased quantitative insulin sensitivity check index (0.01 ± 0.02 vs. 0.002 ± 0.01, p = 0.02) compared with the placebo. Additionally, there was a significant decrease in high-sensitivity C-reactive protein (-815.3 ± 1,786.2 vs. 717.5 ± 1,827.3 ng/mL, p = 0.002) and a significant increase in total antioxidant capacity (113.4 ± 137.4 vs. -53.7 ± 186.7 mmol/L, p < 0.001) following the supplementation of vitamin D compared with the placebo. CONCLUSIONS: Vitamin D3 supplementation for 6 months among women with CIN2/3 had beneficial effects on CIN1/2/3 recurrence and metabolic status; however, it did not affect CIN2/3 recurrence.

Clinical investigation of the safety and efficacy of a cervical intraepithelial neoplasia treatment using a hyperthermia device that uses heat induced by alternating magnetic fields.

Multiple techniques have been used for the conservative treatment of high-grade cervical intraepithelial neoplasia (HG-CIN) in women of fertile age. Conization has been associated with stenosis of the cervix and a decrease in cervical mucus secretion, in addition to the increase in the risk of cervical canal shortening and problems during the perinatal period, including premature birth and premature rupture of membranes. Although the laser transpiration technique does not cause shortening of the cervical canal, it is associated with the recurrent risk of deep residual disease. The present study aimed to investigate the therapeutic safety and efficacy of the therapy performed using the transaction magnetic field induction heating device, AMTC400, in fertile patients with HG-CIN (excluding carcinoma in situ). Four premenopausal patients with CIN3 and high-risk human papilloma virus (HPV)-positive were treated using an AMTC400. Chronological colposcopic findings, high-risk HPV, final histological findings with conization and follow-up data were evaluated. All the treatments were successfully performed on the in-patients without anesthesia. Intra- and postoperative complications included minor pain and bleeding in all cases. Two of the cases (50%) were high-risk HPV-negative following the treatments. All cases exhibited a change in the observed color (to white), and subsequent epithelization following treatment. Although cytological analysis at 5 weeks following the treatment confirmed the cases were negative for intraepithelial lesions and malignancies, a definitive histology with conization 6 weeks following the treatment confirmed CIN1 and koilocytosis in all cases. The assessment of treatment effectiveness was determined as a moderate improvement in all cases. In conclusion, thermotherapy applied using AMTC400 represented a safe and effective treatment for HG-CIN in women of fertile age. However, additional improvements associated with the site of puncture needles are required. Further studies are required to confirm the long-term efficacy and reproductive outcomes.

Effects of long-term folate supplementation on metabolic status and regression of cervical intraepithelial neoplasia: A randomized, double-blind, placebo-controlled trial.

OBJECTIVE: This study was conducted to determine the effects of long-term folate supplementation on regression and metabolic status of patients with cervical intraepithelial neoplasia grade 1 (CIN1). METHODS: This randomized, double-blind, placebo-controlled trial was performed among 58 women diagnosed with CIN1, ages 18 to 55 y old. Participants were randomly divided into two groups to receive 5 mg/d folate supplements (n = 29) or placebo (n = 29) for 6 mo. Fasting blood samples were taken at baseline and 6 mo after intervention to quantify related markers. RESULTS: A greater percentage of women in the folate group had regressed CIN1 (83.3 versus 52.0%, P = 0.019) than those in the placebo group. Long-term folate supplementation resulted in a significant decrease in serum insulin levels (-1.6 ± 6.2 versus +2.6 ± 6.9 µIU/mL, P = 0.018) and homeostatic model assessment-beta cell function (HOMA-B) (-13.0 ± 39.0 versus +11.2 ± 42.3, P = 0.028) compared with the placebo. Additionally, plasma glutathione (GSH) levels were significantly increased (+81.5 ± 264.1 versus -220.9 ± 342.5 µmol/L, P < 0.001) and malondialdehyde (MDA) levels were significantly reduced (-1.0 ± 1.1 versus +0.1 ± 1.6 µmol/L, P = 0.004) in the folate group compared to the placebo. CONCLUSIONS: Taken together, folate supplementation (5 mg/d) for 6 mo among women with CIN1 resulted in its regression as well as led to decreased serum insulin, HOMA-B, plasma MDA and increased plasma GSH levels; however, it did not affect other metabolic profiles.

The favourable effects of long-term selenium supplementation on regression of cervical tissues and metabolic profiles of patients with cervical intraepithelial neoplasia: a randomised, double-blind, placebo-controlled trial.

This study was conducted to assess the effects of long-term Se administration on the regression and metabolic status of patients with cervical intraepithelial neoplasia grade 1 (CIN1). This randomised, double-blind, placebo-controlled trial was carried out among fifty-eight women diagnosed with CIN1. To diagnose CIN1, we used specific diagnostic procedures of biopsy, pathological diagnosis and colposcopy. Patients were randomly assigned to two groups to receive 200 µg Se supplements as Se yeast (n 28) or placebo (n 28) daily for 6 months. After 6 months of taking Se supplements, a greater percentage of women in the Se group had regressed CIN1 (88·0 v. 56·0 %; P=0·01) compared with those in the placebo group. Long-term Se supplementation, compared with the placebo, resulted in significant decreases in fasting plasma glucose levels (-0·37 (sd 0·32) v. +0·07 (sd 0·63) mmol/l; P=0·002), serum insulin levels (-28·8 (sd 31·2) v. +13·2 (sd 40·2) pmol/l; P<0·001), homeostatic model assessment of insulin resistance values (-1·3 (se 1·3) v. +0·5 (se 1·4); P<0·001) and a significant elevation in quantitative insulin sensitivity check index (+0·03 (sd 0·03) v. -0·01 (sd 0·01); P<0·001). In addition, patients who received Se supplements had significantly decreased serum TAG (-0·14 (sd 0·55) v. +0·15 (sd 0·38) mmol/l; P=0·02) and increased HDL-cholesterol levels (+0·13 (sd 0·21) v. -0·01 (sd 0·15) mmol/l; P=0·003). In addition, compared with the placebo group, there were significant rises in plasma total antioxidant capacity (+186·1 (sd 274·6) v. +42·8 (sd 180·4) mmol/l; P=0·02) and GSH levels (+65·0 (sd 359·8) v. -294·2 (sd 581·8) µmol/l; P=0·007) and a significant decrease in malondialdehyde levels (-1·5 (sd 2·1) v. +0·1 (sd 1·4) µmol/l; P=0·001) among those who took Se supplements. Overall, taking Se supplements among patients with CIN1 led to its regression and had beneficial effects on their metabolic profiles.

Results of a phase II randomized, double-blind, placebo-controlled trial of Polyphenon E in women with persistent high-risk HPV infection and low-grade cervical intraepithelial neoplasia.

OBJECTIVE: In vitro data and pilot data suggest that green tea catechins may possess chemopreventive activity for cervical cancer and precursor lesions. We conducted a randomized, double-blind, placebo-controlled trial of Polyphenon E (decaffeinated and enriched green tea catechin extract) in women with persistent human papillomavirus (HPV) infection and low-grade cervical intraepithelial neoplasia (CIN1) to evaluate the potential of Polyphenon E for cervical cancer prevention. METHODS: Ninety-eight eligible women were randomized to receive either Polyphenon E (containing 800 mg epigallocatechin gallate) or placebo once daily for 4 months. The primary study outcome was oncogenic HPV clearance and clearance of CIN1. RESULTS: Polyphenon E was shown to be acceptable, safe and well tolerated. There was no difference in the response rate by treatment allocation. Complete response, defined as negative for high-risk HPV and normal histopathology, was noted in 7 (17.1%) and 6 (14.6%) women in the Polyphenon E and placebo arms, respectively. Progression, defined as persistent oncogenic HPV with histopathologic evidence of progression, was more common in the Polyphenon E group than in the placebo group [6 (14.6%) vs. 3 (7.7%)]. CONCLUSION: Based on the largest randomized placebo-controlled trial of a green tea extract for HPV related cervical disease, we conclude that 4 months of Polyphenon E intervention did not promote the clearance of persistent high-risk HPV and related CIN1. Further studies may be necessary to better delineate the risk factors for persistent HPV infection and biology of the disease to facilitate the evaluation of chemopreventive strategies.

p16INK4a como predictor de evolución clínica en pacientes con neoplasia intraepitelial cervical de bajo grado (NIC-I): serie de casos / p16INK4a as a predictor of clinical outcome in patients with low grade-cervical intraepithelial neoplasia

El diagnóstico morfológico de neoplasia intraepitelial cervical de bajo grado (NIC-I) no permite determinar su real riesgo de progresión a cáncer de cérvix, llevando a seguimiento estricto a un alto número de pacientes cuyas lesiones, en su mayoría, regresarán espontáneamente. La detección de p16INK4A se ha propuesto como biomarcador que permite diferenciar entre infección productiva-autolimitada por virus del papiloma humano (VPH) y transformación celular inducida por cepas oncogénicas del VPH, sin embargo, es necesario aportar evidencias de su capacidad predictiva. Se presenta una serie de 14 casos de NIC-I con detección inmunohistoquímica de p16INK4a en biopsia de cérvix (8 positivos y 6 negativos), cuya revisión retrospectiva de historial clínico de más de 12 meses de seguimiento cito-histopatológico, permite describir regresión espontánea en todos los casos p16INK4a negativo y en 3 casos p16INK4a positivo (37,5 por ciento). Los hallazgos en esta serie coinciden con lo descrito en estudios previos en los que se ha demostrado el valor predictivo negativo del marcador para descartar riesgo de progresión-persistencia y evitar seguimientos y tratamientos innecesarios. Además señalan debilidades a evaluar respecto al valor predictivo positivo de la prueba, al no discriminar algunos factores independientes de la transformación celular, determinantes en la progresión-persistencia de la NIC-I, como lo son variables genéticas y/o inmunológicas del huésped.

The morphological diagnosis of low grade-cervical intraepithelial neoplasia (CIN-1) can not determine its true risk of progression to cervical cancer, leading to strict adherence to a high number of patients whose lesions, most will return spontaneously. The detection of p16INK4a has been proposed as biomarker to differentiate between productive infection self-limiting by human papillomavirus (HPV) and cell transformation induced by oncogenic strains of HPV, however, it is necessary provide evidence of its predictive capacity. We present a series of 14 cases of CIN-1 with immunohistochemical detection of p16INK4a in cervical biopsy (8 positive and 6 negative), whose retrospective review of medical records of more than 12 months of cyto-histopathological follow, can describe spontaneous regression in all cases p16INK4a negative and in 3 cases p16INK4a positive (37.5 percent). The findings in this series of cases coincide with that described in previous studies that has been demonstrated the negative predictive value of the marker to exclude risk of progression-persistence and avoid follow-ups and unnecessary treatments. Additionally, these indicates weaknesses to evaluate about the positive predictive value of the test, by not discriminating factors independent of cellular transformation, determining the progression-persistent CIN-1, such as genetic and / or immunologic variables of the host.

Efficacy of human papillomavirus vaccines including cross protection : A review of recent evidence / 대한산부인과학회지

The efficacy and immunogenicity of human papillomavirus (HPV) vaccines has proven excellent in several phase 2 and phase 3 trials involving tens of thousand women. Two versions of HPV vaccine had been developed, both target HPV 16 and HPV 18, which involve approximately 70% of cervical cancer. We have summarized the recent review of all randomized controlled trials in which vaccines against HPV were compared with placebo regarding efficacy, safety, and immunogenicity. Both vaccines have an excellent safety profile, are highly immunogenic, and have atributed complete type specific protection against persistent infection and associated lesions in fully vaccinated girls and young women. Data strongly suggest that both vaccines can have a variable level of cross protection against HPV types genetically and antigenically-closely related to vaccine types. Demonstration of cross protection against combined endpoints [cervical intraepithelial neoplasia (CIN) 2/3 and adenocarcinoma in situ] for HPV-31 has been reached for the quadrivalent vaccine. Bivalent HPV vaccine showed significant type-specific cross-protection against CIN2+ associated with HPV-31, HPV-33, and HPV-45. The bivalent vaccine is also registered for above age 26 in Australia, Israel and Korea. In our country, we have already set up the clinical guideline of both vaccines. Although these prophylactic vaccination is likely to provide important gains in the prevention of cervical cancer, we should have need to establish the new screening guideline in post-vaccination period and to make next version of vaccination-guidelines related of specific subgroups of patients who would benefit from the vaccine (women older than 26 years, boys, and men).

Selenium, Manganese, Copper and Zinc Contents in Serum of Patients with Cervical Intraepithelial Neoplasia / 대한지역사회영양학회지

The purpose of this study was to investigate the implications of dietary intake and the level of serum micronutrients (Se, Mn, Cu, Zn), lipid peroxidation, and antioxidant capacity in Korean women with cervical intraepithelial neoplasia (CIN). From October 2002 to March 2003, 50 patients diagnosed with CIN (confirmed with colposcopy directed biopsy) and 50 patients without any cervical disease as the control group were enrolled in the study at the Department of Gynecology Cancer Center at Samsung Cheil Hospital. Animal fat intake in CIN group was significantly higher than that of the control group, but plant protein intake in the CIN group was significantly lower than that of the Control group. Energy and zink intakes were similar in the two groups. The serum concentration of antioxidant minerals in the CIN group were not signifi-cantly different from the control group. The total radical trapping antioxidant potential concentration of plasma was sig-nificantly lower in the CIN group (1.12 mM) than in the control group (1.25 mM)(p < 0.05). But MDA (malondialde-hyde) of serum was significantly higher in the CIN group (7.60 mM) than in the control group (4.99 mM)(p < 0.005). The serum selenium concentration of the control group showed significant positive correlation with the MDA level (r = 0.311). These findings are suggestive of protective roles for healthy dietary habit including increasing antioxidant nut-rients and decreasing intake of fat.

Management of High Grade Cervical Intraepithelial Neoplasia Using CO2 Laser Conization and LEEP / 대한부인종양콜포스코피학회잡지

Between June 1990 and May 1994, 350 laser conization and 200 LEEP were performed. Indications of conization were that directed biopsy specimen was proved CIN II, III or suggests possible microinvasion. In all the cases the procedures were carried out with the patients under local anesthesia. Excisional cone sections(6,600) were evaluated for lesion length,depth and margin status. Invasive cancer was found in 5(1.4%) women of laser group. Operative time was shorter LEEP group than laser group significantly. In laser group, 25(8.3%) women had bleeding that required treatment. One case(0.3%) of pelvic infection and 7 cases(2.3%) of cervical stenosis were observed. In LEEP group, 10(5.3%) women had bleeding, 3(1.6%) patients became cervical stenosis. The diameter of bumed tissue was 0.28mm in laser group and 0.25mm in LEEP group. Success rate were 97.4% in former and 96.3% in later. This study demontrated that CO2 laser conization and LEEP were effective methods for treating high grade cervical intraepithelial neoplasia and added benefit of preserving reproductive function and rule out invasive carcinoma.