妊娠合并宫颈疾病诊治进展

妊娠期宫颈可发生炎性疾病,人乳头瘤病毒(HPV)感染,宫颈上皮内瘤样病变(CIN)甚至宫颈浸润癌。近年来,对妊娠期宫颈疾病的关注度逐渐上升。妊娠合并宫颈疾病可通过细胞学检查、HPV-DNA检测、P16/Ki67双联染色、阴道镜、活检和宫颈锥切等进行诊断。治疗方面妊娠合并HPV感染没有特别治疗;CIN患者排除宫颈浸润癌后可行细胞学及阴道镜随访至分娩;妊娠合并宫颈癌的处理较为复杂,需要考虑到肿瘤治疗与胎儿安全之间的平衡,治疗需综合考虑肿瘤大小、淋巴结转移情况及患者继续妊娠的意愿。分娩时机及分娩方式方面,合并宫颈感染性疾病及CIN的妊娠患者均按照产科处理;Ⅰa1期、间质浸润深度3 mm并且切缘阴性宫颈癌患者可妊娠至足月阴道试产,对于更高期别患者建议胎儿成熟后剖宫产终止妊娠。     

妊娠合并宫颈病变分娩时机及方式的选择

妊娠合并宫颈病变主要指妊娠合并宫颈上皮内瘤变(CIN)及宫颈浸润癌。妊娠合并CIN患者可以妊娠至足月,经阴道分娩;妊娠合并宫颈癌的处理(分娩时机及分娩方式)依赖于宫颈癌分期、淋巴结有无转移、肿瘤的组织学分型、孕周及患者是否希望继续妊娠。     

2006 consensus guidelines for the management of women with cervical intraepithelial neoplasia or adenocarcinoma in situ

A group of 146 experts representing 29 organizations and professional societies met Sept. 18-19, 2006, in Bethesda, MD, to develop revised evidence-based, consensus guidelines for managing women with abnormal cervical cancer screening tests. The management of low-grade cervical intraepithelial neoplasia (CIN) grade 1 has been modified significantly. Previously, management depended on whether colposcopy was satisfactory and treatment using ablative or excisional was acceptable for all women with CIN 1. In the new guidelines, cytological follow-up is the only recommended management option for women with CIN 1 who have low-grade referral cervical cytology, regardless of whether the colposcopic examination is satisfactory. Treatment is particularly discouraged in adolescents. The basic management of women in the general population with CIN 2,3 underwent only minor modifications, but options for the conservative management of adolescents with CIN 2,3 have been expanded. Moreover, management recommendations for women with biopsy-confirmed adenocarcinoma in situ are now included.     

宫颈上皮内瘤变分子生物学指标的研究进展

宫颈癌是妇科最常见的恶性肿瘤之一,近年来宫颈癌的发病率逐年上升,且有年轻化趋势。宫颈上皮内瘤变（CIN）是由高危型人乳头瘤病毒（HPV）的持续性感染引起的,是宫颈癌的癌前病变,其反映宫颈癌发生发展中的连续过程,从CIN发展为宫颈癌需要较长的时间。在CIN的进展过程中,许多基因结构和功能都会发生变化。近年来的研究发现,在CIN和宫颈癌的组织中存在着一些表达异常的生物学标记物,这些生物学标记物与前驱病变级别和肿瘤是否发生转移相关,将这些基因作为CIN进展的分子生物学标志物进行检测,早期发现和诊断宫颈癌已成为目前研究的热点。综述CIN研究的前沿性分子生物学指标。     

Colposcopy and cervical intraepithelial neoplasia

Cervical cancer is both preventable and curable. It has a long natural history with a prolonged pre-cancerous phase that is easily detectable and treatable. Exfoliative cytology has been the mainstay for screening of cervical intra-epithelial neoplasia (CIN). Assessment of women presenting with abnormal cervical cytology and the selection of those requiring treatment relied mainly on colposcopic impressions of the cervical transformation zone and the histological appraisal of directed punch biopsies. The need to maximise clinical resources, achieve quicker and more effective management of patients, limit postoperative complications and preserve reproductive function has led to the popularity of local excisional methods for cervical premalignancy. Although the cure rates for all local ablative and excisional methods are more than 90% after one treatment, the excisional methods provide a more reliable histopathological diagnosis and the patient can be treated at the initial visit. The recognition that persistent infection with oncogenic human papillomavirus (HPV) causes cervical cancer has led to the development of new HPV tests/biomarkers and prophylactic vaccines against HPV. The HPV DNA test that targets the viral DNA has been introduced as a test of cure after CIN treatment and as a triage tool in women presenting with borderline or low-grade findings at cytology. HPV DNA test will be introduced in primary screening in the future. The national HPV immunisation programme was initiated in the NHS in September 2008. The vaccines are safe, well tolerated and highly efficacious in HPV naive women.     

Guidelines for screening and treatment of cervical disease in the adolescent

BACKGROUND: The last decade has seen a significant increase in our knowledge of HPV infection and its natural history. The advent of liquid-based cytology and HPV testing has changed the way we approach patients with abnormal Pap tests. The objective is to summarize some of the key evidence that lead to the American Society for Colposcopy and Cervical Pathology (ASCCP) guidelines for the management of abnormal cytology and histology and the American Cancer Society (ACS) cervical cancer screening guideline as they pertain to adolescents. METHODS: The critical publications responsible for the recent ASCCP guidelines as well as the ACS recommendations for cervical cancer screening were reviewed. RESULTS: Sexually active adolescents are frequently infected by HPV. The natural history of these infections is one with a high rate of resolution. The typical HPV infection will resolve in approximately one year. The ACS has recommended that Pap test screening begin at 21, or 3 years after the onset of sexual activity. The ASCCP guidelines for the management of CIN 1 conclude that observation is the preferred therapy. These recommendations reflect our improved understanding of the natural history of HPV infection. CONCLUSIONS: Adolescents frequently experience transient HPV infections. As our understanding of the natural history of these infections has improved major national organizations have changed the recommendations for the screening of cervical disease and treatment of low-grade cervical abnormalities. The health care community servicing adolescents should incorporate these recommendations into daily practice.     

Clinical management of cervical intraepithelial neoplasia in pregnant and postpartum women

Objective

To evaluate the clinical management of cervical intraepithelial neoplasia (CIN) and cervical microinvasive squamous cell carcinoma in pregnant and postpartum women.

Methods

This prospective study enrolled 27,230 pregnant women undergoing routine gestational examinations between August 1, 2007 and July 31, 2010 in the Beijing Obstetrics and Gynecology Hospital, Capital Medical University. Colposcopy and cervical biopsy were performed for patients with abnormal Thin Prep^® Papanicolaou test (TCT) results. Periodic colposcopy was performed every 8–12 weeks and cervical biopsy was performed if progression was suspected. Cervical cold knife conization was recommended to patients diagnosed with CINIII or microinvasive cervical carcinoma 6–12 weeks after delivery.

Results

A total of 2,260 patients had abnormal TCT results (8.12 %). Colposcopy and cervical biopsy were performed for 369 patients. Fifteen patients had microinvasive squamous cell carcinoma, 116 patients had cervicitis, and the number of CIN patients with histological grades I, II, and III were 124, 49, and 65, respectively. Tumor progression during pregnancy was found in 253 patients (CINI or above). Prognosis varied depending on the highest grade of pathological diagnosis results during pregnancy or initial pathological diagnosis results performed 6–12 weeks after delivery by cervical biopsy under colposcopy. Treatment and follow-up were carried out according to diagnoses, state of progression, and reversion (if any).

Conclusion

These findings underline a need for cervical lesion screening for all women during pregnancy, and colposcopy should be performed for pregnant women who have abnormal TCT results. Appropriate treatment and follow-up were recommended according to different diagnosis of CIN.     

内蒙古东部地区宫颈癌及宫颈癌前病变的人群筛查研究

目的探讨内蒙古东部地区妇女宫颈癌及宫颈癌前病变的疾病状况。方法本研究是以人群为基础的横断面筛查研究,2005—2010年间,选取内蒙古东部地区三个筛查点的18～69岁的妇女作为目标人群,采集其宫颈脱落细胞标本,细胞学诊断采用TBS2001分级系统,异常者进行阴道镜检,有病变者直接取活检明确诊断。细胞学阳性定义为意义不明确的非典型鳞状上皮细胞（ASCUS）以及更高度病变,以组织病理学为金标准,分析不同年龄组,地区和民族患者宫颈癌及宫颈上皮内瘤变（CIN）的发病趋势。结果①内蒙东部地区全人群、蒙族和汉族妇女异常细胞学（ASCUS＋）的检出率分别为6.56%、8.03%和6.06%;其中蒙族妇女细胞学异常病变的检出率高于汉族妇女;②病理结果显示：内蒙东部地区宫颈上皮内瘤变（CIN1）的患病率为2.4%,〉CIN2的患病率为1.47%,宫颈早浸癌的患病率为0.04%;蒙族妇女患病率较汉族高,通辽地区的患病率较呼盟和赤峰地区高。其中蒙族妇女各级病变的患病率分别为：CIN12.87%、〉CIN21.80%、早期浸润癌0.10%;汉族分别为：2.25%、1.36%、0.03%。疾病年龄分布：CIN1现患率最高为35岁之前年龄组,〉CIN2的高发年龄为40～49岁,宫颈癌的高发年龄为50～54岁。结论①内蒙东部地区蒙古族妇女宫颈癌及癌前病变的现患率高于汉族妇女;②在内蒙东部地区宫颈癌的筛查年龄段应涵盖30～55岁年龄组,其中40～55岁年龄组为重点人群,应在该年龄段加强宫颈癌的筛查。     

The use of electrical impedance spectroscopy in the detection of cervical intraepithelial neoplasia

The objective of this study was to assess the performance of cervical impedance spectroscopy in the detection of cervical intraepithelial neoplasia (CIN) using the new MKIII impedance probe. A prospective observational study recruited women referred to colposcopy with an abnormal Papanicolaou smear. A pencil probe incorporating four gold electrodes was used to measure electrical impedance spectra from cervical epithelium. Colposcopy examinations, including probe positioning, were video recorded to allow for correlation between results obtained from colposcopic impression, histopathologic examination of colposcopic punch biopsies, and impedance measurements. Cervical impedance-derived parameters R, S, R/S, C, and Fc were assessed to see if significant difference in values obtained in CIN and normal epithelium existed. The performance of the probe in identifying women with CIN was also assessed. One hundred seventy-six women were recruited and 1168 points analyzed. Parameters R, S, and Fc showed significant separation of CIN or squamous intraepithelial lesion (SIL) from squamous, mature metaplastic, and columnar epithelium. Sensitivities of 74% and specificity of 53% can be achieved in identifying CIN 2/3 (High-grade SIL) in screened women. We conclude that cervical impedance spectrometry provides a potentially promising real-time screening tool for CIN with similar sensitivity and specificity to currently used screening tests. Further research is ongoing to develop the probe for potential clinical use.     

妊娠期宫颈癌筛查

妊娠期宫颈癌是严重影响母儿健康的围妊娠期合并症。了解妊娠期的生理特点与宫颈癌的关系,掌握不同妊娠期宫颈癌的特点及筛查方法,建立临床医师对妊娠期宫颈癌的筛查规范,加强妊娠期宫颈癌的早期筛查,对减少育龄妇女及围产儿病死率具有重要意义。     

子宫颈上皮内瘤变治疗过度与不足的得失分析

子宫颈上皮内瘤变是子宫颈癌的癌前病变,合理干预子宫颈上皮内瘤变是防治子宫颈癌的主要措施之一。文章就子宫颈上皮内瘤变干预过程出现的治疗过度与不足的原因和结果加以剖析,以期待有效阻断病变发展。     

宫颈上皮内瘤变的进展预警

宫颈上皮内瘤变（cervical intraepithelial neoplasia,CIN）是宫颈浸润癌的癌前病变。CIN的发生和进展是一个多因素、多水平的过程。大量研究证实高危型人乳头瘤病毒（human papillomavirus,HPV）持续感染是宫颈癌及CIN的重要致病原因之一,其与宫颈癌的发生、发展有着密切的关系。随着分子生物学的发展和测序技术的进步,阴道微生物与HPV在CIN和宫颈癌的协同作用逐渐被认识。而寻找和探索对CIN进展有判断价值的生物标志物,预警CIN的进展已经成为目前宫颈病变研究的一大热点。综述与CIN进展有关的原因、影响因素及标志物等,以期预警CIN的进展,正确分流及规范管理CIN。     

妊娠合并宫颈癌治疗现状及进展

宫颈癌是妊娠期间最常见的妇科恶性肿瘤之一。妊娠合并宫颈癌的治疗需要综合考虑肿瘤期别、病理类型、妊娠孕周、淋巴结状态及孕妇对于妊娠的意愿。尤其对于要求继续妊娠的患者,需遵循个体化原则,强调多学科诊治。文章就目前妊娠期合并宫颈癌的研究现状进行总结阐述。     

Abnormal pap smear and cervical cancer in pregnancy

Pregnancy represents a unique opportunity to screen reproductive age women for cervical cancer and abnormal cervical cytology is relatively common in this population. In the absence of large, prospective clinical trials investigating the optimal management strategies for cervical dysplasia in pregnant women, consensus guidelines established by the American Society for Colposcopy and Cervical Pathology is available with considerations to this special patient population. Modalities for evaluation and management algorithms are reviewed and summarized from largely case series of pregnant women with cervical dysplasia and cervical cancer.     

ⅠA1期子宫颈癌早期诊断与治疗路径分析

目的探讨ⅠA1期子宫颈癌早期诊断和治疗的临床路径。方法对2003年1月至2012年12月诊断及治疗的71例ⅠA1期子宫颈癌患者的临床资料进行回顾性分析。结果在同期581例子宫颈癌患者中,ⅠA1期子宫颈癌患者71例,占12.2%,患者平均年龄（45.0±10.4）岁。在71例ⅠA1期子宫颈癌患者中,70例（98.6%）患者病理类型为鳞状细胞癌;29例（40.8%）患者有异常阴道出血或排液;67例（94.9%）患者有不同程度的宫颈细胞学异常,65例（91.1%）患者高危型人乳头瘤病毒（HR-HPV）阳性;32例（45.1%）患者阴道镜下多点活检病理提示早期浸润癌,62例（87.8%）患者子宫颈锥切术后病理诊断。结论子宫颈癌ⅠA1期患者的早期发现主要通过子宫颈癌筛查,对于筛查异常者及时行阴道镜及病理检查,高度可疑子宫颈癌前病变及浸润癌者建议及时行子宫颈锥切术。     

Caring for Women With Abnormal Papanicolaou Tests During Pregnancy

The Papanicolaou (Pap) test is one of the best screening tests available for cancer detection and has achieved widespread acceptance among women. Pregnancy provides a valuable opportunity to educate and screen women for cervical cancer when receiving prenatal care. However, evolving knowledge about the course of human papillomavirus infection (HPV) in women, new technologies, and the advent of vaccines are driving radical changes in practice and new ways to consider cervical cancer screening. Modifications in the 2006 Consensus Guidelines for the Management of Women with Abnormal Cervical Cancer Screening Tests are most evident among adolescents. Because of high rates of HPV regression, pregnant adolescents with minor Pap abnormalities may now be followed rather than referred for immediate colposcopy. Postponing colposcopy in pregnant, reproductive‐age women with minor Pap changes until after delivery is now acceptable. Pregnant immunocompromised women with abnormal Pap tests are followed similarly to pregnant women in the general population. While a strong evidence base is gradually emerging to support guideline revisions, the highest quality evidence may not yet be available for all recommendations. Midwives can keep abreast of the science while using clinical judgment to provide safe and expert cancer screening care to women.     

Colposcopy and cervical intraepithelial neoplasia

Cervical cancer is both preventable and curable. It has a long natural history with a prolonged pre-cancerous phase that is easily detectable and treatable. Exfoliative cervical cytology remains the mainstay for screening of pre-cancerous lesions (cervical intraepithelial neoplasia, CIN). Assessment of women presenting with abnormal cervical cytology and the selection of those requiring treatment relies mainly on colposcopic impressions of the cervical transformation zone and histological appraisal of directed punch biopsies. There is variation in the assessment of cytology, colposcopy and histology findings, and therefore the ‘final’ diagnosis involve of all three disciplines. The need to maximise clinical resources, achieve quicker and more effective management of patients, limit postoperative complications and preserve reproductive function has led to the popularity of local excisional methods for cervical premalignancy. Although the cure rates for all local ablative and excisional methods are more than 90% after one treatment, the excisional methods provide a more reliable histopathological diagnosis and the patient may be treated at the initial visit. Cure rates for CIN correlate principally with the extent of the CIN. More than 95% of cervical cancer cases are associated with oncogenic types of human papillomavirus. Important advances have been made in developing recombinant vaccines to prevent and treat this infection. Clinical trials of preventive and therapeutic vaccines have been reported and the vaccine is now available for use.     

Cervical cancer prevention: the impact of HPV vaccination

Cervical cancer remains a critical public health problem that is second only to breast cancer in overall disease burden for women throughout the world. In spite of the success of cervical cancer screening, Pap cytology screening is yet to be effectively implemented or has failed to reduce cervical cancer rates to an appreciable extent. Screening appears to benefit only a small fraction of women although a much larger percentage endures the inconvenience of the Pap test in order to avoid cervical cancer. The establishment of Human Papillomavirus (HPV) infection as the necessary cause of cervical precancers and cancers provides a tremendous opportunity for cervical cancer prevention through vaccination. HPV 16 and 18 which cause 70% of cervical cancers worldwide. Thus a prophylactic vaccine to prevent HPV related precancerous lesions and cancers would save lives, reduce the need for costly medical procedures and provide both women and communities throughout the world with substantial benefits. Based on the induction of neutralizing antibodies by non infectious Virus Like Particles (VLP) of L1 capside protein, prophylactic HPV vaccines have consistently induced high titter of neutralizing antibodies with minimal side effects and induce more than 90% protection from persistent HPV 16-18 infection and HPV 16 and 18 associated high-grade Cervical Intraepithelial Neoplasia (CIN) in proof of concept efficacy trials. HPV 16-18 vaccination will prevent HPV16-18 incident infection, and subsequently decrease in 90% the frequency of abnormal Pap attributable to these types and in about 50% overall abnormal Pap. HPV vaccination will reduce the number of women who require colposcopy, biopsy and cervical treatment for precancerous cervical lesions. The level of protection from death due to cervical cancer could exceed 95%. Three large phases prophylactic HPV VLP trials are now in progress and will form the basis for licensing of candidate vaccines in 2006. HPV vaccination targeting young female adolescents, aged 11 to 16 years, with a catch-up of those aged 17-25 years, would be a strategy to be addressed. Cervical cancer screening strategies, that will be cost-effective for the proper surveillance of women protected by HPV vaccination, are under analysis.     

阴道镜下宫颈活组织检查诊断孕妇宫颈病变的临床研究

目的 探讨阴道镜下官颈活组织检查(活检)诊断孕妇宫颈病变的临床价值和安全性.方法 采用队列研究方法,选择2007年8月1日至2009年2月28日在北京妇产医院产科门诊初次检查的孕13～34周、1年内未进行过宫颈液基薄层细胞学检查(TCT)的孕妇,先进行TCT筛查,对TCT结果异常者,在知情同意后进行阴道镜检查和阴道镜下宫颈活检.结果 (1)TCT:TCT筛查孕妇共计17 828例,其中TCT结果异常1502例,发生率为8.425%.(2)阴道镜检查:204例孕妇进行了阴道镜检查.阴道镜图像满意度为92.6%(189/204),阴道镜拟诊宫颈炎或宫颈上皮内瘤变(CIN)Ⅰ 125例,CIN Ⅱ25例,CIN Ⅲ或宫颈鳞状细胞癌(SCC)54例.(3)阴道镜下宫颈活检病理结果:204例行阴道镜检查者全部进行了宫颈活检,病理结果为宫颈炎及宫颈湿疣共33例,CIN Ⅰ 95例、CIN Ⅱ28例、CIN Ⅲ36例(包括官颈原位癌13例)、SCC Ⅰ a期12例.(4)符合度:与宫颈活检病理结果比较,阴道镜检查拟诊炎症和CIN Ⅰ 125例,其中113例与宫颈活检病理结果相同,符合率为90.4%(113/125),125例炎症和CIN Ⅰ患者中无一例病理结果为SCC.阴道镜检查拟诊CIN Ⅲ或SCC共54例中,23例活检病理结果为CIN Ⅲ、10例为SCC Ⅰ a期,符合率为61.1%(33/54例).(5)并发症:阴道镜检查及官颈活枪后,8例孕妇因官颈局部压迫止血无效行创面缝合止血,发生率3.9%(8/204),未发生其他与阴道镜检查和宫颈活检相关的不良事件.结论 对1年内未进行宫颈细胞学筛杏的孕妇进行TCT检查是必要的,对TCT结果异常者应进行阴道镜检查,阴道镜检查拟诊官颈炎或CIN Ⅰ者可以随诊,对阴道镜检查拟诊CIN Ⅱ及更高级别宫颈病变的孕妇,应行阴道镜下宫颈活检以明确病理学诊断.     

Urinary catheter stent placement for treatment of cervical stenosis

BACKGROUND: Cervical stenosis is an uncommon condition that may result in significant distress in premenopausal women. Those affected may present with amenorrhoea and associated cyclical, monthly pain, infertility and haematotrachelos/haematometra. AIM: To describe a safe, easy and effective treatment method for cervical stenosis. Methods: The cervical canal is identified and dilated under ultrasound guidance. A urinary catheter stent is then placed in the cervical canal for two weeks. RESULTS: Of the five patients who underwent treatment for cervical stenosis, all had normal menstrual cycles restored. Four of these patients successfully became pregnant after treatment. Three of the four patients progressed to uncomplicated births at term (gestation). The fourth patient underwent a termination of pregnancy in the second trimester for a fetal abnormality. CONCLUSIONS: Cervical dilatation under ultrasound guidance with temporary urinary catheter stent placement appears to be both effective and safe in the treatment of cervical stenosis. Pregnancy outcomes after treatment were optimal in our case series.