Aneuploidy screening: what test should I use?

Screening for the risk of fetal aneuploidy can be effectively performed in either the first or second trimester. When obtained independently, the interpretation of those data is straightforward. However, the effectiveness of screening can be enhanced by combining studies performed in each trimester in a variety of ways. In this commentary we will define and discuss both the advantages and disadvantages of using integrated, stepwise, sequential or contingency screening for risk assessment of fetal aneuploidy.     

Genetic screening for infertility: When should it be done?

Depending on the clinical findings, the infertile male patient needs genetic evaluation. Karyotype analysis and Y-chromosomal microdeletion screening should be performed in patients with azoospermia or severe oligozoospermia in order to rule out structural chromosomal abnormalities, Klinefelter syndrome and Y chromosome microdeletions. Infertile patients with obstructive azoospermia need cystic fibrosis transmembrane receptor gene screening, while in patients with hypogonadotropic hypogonadism mutation screening may be performed according to clinical features. All genetic analyses should be accompanied by expert counseling by a clinical genetist both in male and female patients.Primary amenorrhea should be investigated by karyotype analysis and selected mutation screening according to the patient's clinical features. Karyotype analyses and FMR1 gene screening is recommended in cases of POF. At present the infertility of patients with POF cannot be restored if the diagnosis is made after complete follicular depletion, but in some cases, early diagnosis by genetic investigation may instead lead to the advice of early conception or oocyte harvesting and preservation. In addition, the accumulation and annotation of array comparative genomic hybridization data might, in the near future, lead to the identification of pathogenetic copy number variations and genes involved in POF. Karyotype analysis of both partners is recommended in all couples with recurrent pregnancy loss. No routine genetic test can be recommended so far in patients with PCOS.     

Cervical cancer screening of HIV-positive women: is a prolongation of the screening interval meaningful?

OBJECTIVE: Cervical cancer screening guidelines stated recently that the screening interval of healthy women can be extended up to 3 years. Can those recommendations be applied for high risk populations? MATERIAL AND METHODS: In a prospective setting 305 HIV-positive women have been enrolled in this analysis between September 2000 and December 2003. Patients have been characterized according to HPV (human papilloma virus) prevalence, CIN (cervical intraepithelial neoplasia) incidence and CD4 cell count. RESULTS: 41 % of all HIV-positive women were HPV positive (oncogene subtypes). In patients with diminished CD4 cells the HPV prevalence increased to 60 % (54/90). CIN was found in 27 % (83/305) women. CIN was more frequent by HPV-positive women with a CD4 cell count < 200 mm (3) (52 %, 38/72). The CIN incidence was also high in HIV-positive women with negative HPV infection and diminished CD4 cell count (39 %, 7/18 vs.7 %, 11/161). CONCLUSIONS: The current cervical cancer screening guidelines are not helpful in HIV-positive women. The CIN incidence is significantly higher as in the HIV-positive population. For this reason this high risk population as e. g. HIV-infected women need an intensive care of diagnostic tools and short screening intervals to detect CIN.     

Comprehensive assessment of fetal wellbeing: which Doppler tests should be performed?

PURPOSE OF REVIEW: Doppler applications in pregnancy are expanding exponentially. Flow velocity waveforms provide important information 12 weeks to term, from maternal vessels, placental circulation and fetal systemic vessels, with implications for both mother and fetus. As applications proliferate, awareness of the complexity of fetal and placental circulations, in normal pregnancy and in sequential responses to compromise, has also grown. The necessary data are now available to establish core values in Doppler evaluation for at-risk pregnancies. RECENT FINDINGS: Uterine arteries depict maternal vascular effects of the invading placenta, predicting the frequency and severity of pre-eclampsia and intrauterine growth restriction. New evidence suggests early treatment based on this principle, significantly reduces these impacts. Umbilical artery Doppler reflects downstream placental vascular resistance, strongly correlated with intrauterine growth restriction and the multisystem effects of placental deficiency. Abnormalities are progressive, with reduction, loss, and finally a reversal of diastolic flow. When umbilical arteries become abnormal, the differentiation of fetal status requires Doppler information from systemic vessels. Middle cerebral artery changes begin when the redistribution of cardiac output reflects rising placental resistance, demonstrating 'brain sparing' when cerebrovascular dilation occurs. In the compromised intrauterine growth retarded fetus, precordial veins illustrate fetal cardiac function, changing as the respiratory status declines. This Doppler information is combined with biophysical profile scoring to determine the need for and timing of intervention. SUMMARY: Doppler evaluation of at-risk pregnancies provides crucial prognostic and diagnostic detail about placentation and fetal adaptation. What has been research detail is now becoming the standard of care, in comprehensive fetal-maternal assessment.     

HPV E6/E7 mRNA检测在LBC-/HPV+女性临床管理中的应用价值

目的:探讨HPV E6/E7 mRNA检测在LBC-/HPV+女性临床管理中的应用价值。方法:收集2017年12月至2019年9月在临沂市人民医院自愿接受液基细胞学(LBC)联合HR-HPV DNA(包含HPV16/18分型)或HPV E6/E7 mRNA检测进行宫颈癌筛查,结果为LBC-/HPV+且后续转诊阴道镜及组织病理学检查患者628例,以病理诊断结果为金标准,分析比较两种HPV检测方法对LBC-/HPV+患者人群发生高级别及以上宫颈病变(≥HSIL)的风险预测能力。结果:628例LBC-/HPV+患者中,共检出≥HSIL患者80例(12.74%),其中以30～39岁组检出率最高(17.89%)。490例HR-HPV DNA阳性患者≥HSIL总检出率为10.00%(49/490),双+组检出率最高(14.89%,14/94);138例HPV E6/E7 mRNA阳性患者≥HSIL总检出率为22.46%(31/138),16/18/45+组检出率最高(37.78%,17/45)。HPV E6/E7 mRNA阳性组发生≥HSIL的相对危险度(RR值)是HR-HPV DNA阳性组的2.246倍(95%CI为1.493～3.379);16/18/45+组发生≥HSIL的RR值是16/18+组患者的3.169倍(95%CI为1.786～5.622);HPV E6/E7 mRNA其余11型+组发生≥HSIL的RR值是HR-HPV DNA其余12型+组的2.170倍(95%CI为1.115～4.222),差异均有统计学意义(P0.05)。结论:HPV E6/E7 mRNA检测尤其是16/18/45分型检测是LBC-/HPV+患者人群发生≥HSIL的有效风险预测指标,其评价效能优于包含HPV16/18分型的HR-HPV DNA检测;HPV E6/E7 mRNA有望作为HR-HPV DNA阳性但16/18分型阴性患者的进一步分流指标。     

HPV E6/E7 mRNA检测在HPV分型及宫颈疾病筛查中的作用研究

目的探讨人乳头瘤病毒(HPV)E6/E7 m RNA检测在女性宫颈疾病筛查中的作用。方法选取2016年9月至2017年9月贵州医科大学附属医院妇产科门诊和住院部就诊的HPV阳性感染者287例,其中宫颈疾病患者267例[包括宫颈炎、宫颈上皮内瘤变(CIN)Ⅰ~Ⅲ、宫颈癌],阳性感染者中体检无疾病表现及病理学检查无宫颈病变者20例。取患者宫颈脱落细胞用支链DNA技术(简称b-DNA技术)检测高危HPV E6/E7 m RNA,患者同时行宫颈液基薄层细胞检测和HPV分型检测,对不同年龄、HPV分型、阴道细胞学分型(简称TBS分型)及疾病分级的HPV E6/E7 m RNA的诊断价值进行效能分析。结果在不同年龄段内E6/E7阳性和阴性所占比例差异有统计学意义,P0.05,在年龄组≤30岁组和50~60岁组,E6/E7阳性者所占比例最大,分别为85.40%和84.40%;而HPV E6/E7m RNA拷贝数在不同年龄组内差异没有统计学意义。E6/E7结果在单一感染和混合感染,以及单一感染和多重感染间差异无统计学意义;在不同感染型别中,只有HPV 16型随病变严重程度的增加其感染率呈递增趋势(P0.05),其余HPV型与病变严重程度无明显相关性(P0.05)。不同疾病分组间,E6/E7阳性率的分布差异有统计学意义,表现为无宫颈病变组(0)宫颈炎(15.60%)CINⅠ(86.20%)CINⅡ(93.00%)CINⅢ(96.50%)宫颈癌(100.00%),P0.05;E6/E7拷贝数表达差异有统计学意义,表现为宫颈炎1773.89(936.54)CINⅠ4997.74(10 439.75)CINⅡ52 655.02(38 495.10)CINⅢ72 300.12(38 298.57)宫颈癌121 616.68(34 348.59),P0.05。结论在宫颈疾病中检测高危型HPVE6/E7 m RNA的转录对女性宫颈癌高危人群的筛查和诊治具有重要的价值,或可作为进一步分流HPV阳性病人的方法。     

Surgery for early stage cervical cancer: How radical should it be?

Objective

Less radical or non radical surgery for early-stage cervical cancer has been proposed to reduce morbidity while maintaining oncologic outcomes. Given that a standardized approach to conservative surgery is not yet available, we have summarized the literature on less radical surgery to better inform clinical practice.

Methods

MEDLINE R and MEDLINE in-process and non-indexed citations were searched from inception to April 14, 2013 to identify all English-language articles evaluating less-radical or non radical surgery for invasive cervical carcinoma. Articles including patients with squamous cell carcinoma, adenocarcinoma and adenosquamous carcinoma were included and a narrative review of the literature is presented.

Results

Radical surgery is associated with significant adverse effects in terms of urinary function, sexual function, and body image. Radical trachelectomy is an accepted fertility-sparing option, but still leads to morbidity from parametrectomy. The importance of the parametrectomy in patients with small early-stage tumors has been questioned recently, and many studies have found simple hysterectomy and simple trachelectomy can be safe in appropriately selected patients. Cone biopsy may be a fertility-sparing option in those patients with a very low risk of parametrial involvement. Neoadjuvant chemotherapy is also being investigated as a method to reduce the need for radical surgery. Sentinel lymph node biopsy is discussed as a method to reduce the morbidity while increasing the sensitivity of pelvic lymph node assessment in women with early cervical cancers. Finally, the treatment of early adenocarcinoma is addressed.

Conclusions

It appears many women with early-stage cervical cancer can be treated less radically than has been done in the past. Large prospective trials are underway to further define candidates for less-radical surgery.     

宫颈癌及癌前病变组织中Notch1及HPV16 E6/E7表达的研究

目的 探讨Notch1受体和人乳头瘤病毒16感染在宫颈癌前病变和宫颈癌发生发展中的作用。方法 采用免疫组化SP法检测18例宫颈上皮内瘤变（cervical intraepithelial neoplasia,CIN）和35例宫颈癌标本中Notch1受体及HPV16E6/E7蛋白的表达,以34例正常宫颈组织及慢性宫颈炎组织作为对照。比较各组间Notch1及HPV16E6/E7表达的差异,并分析Notch1与HPV16E6/E7表达的关系。结果 Notch1蛋白在细胞胞浆、胞核及胞膜中表达,HPV16E6/E7在细胞核中表达。从对照组到CIN组到宫颈癌组,Notch1及HPV16E6/E7的表达均逐渐增强（P〈0.01）。Notch1的阳性表达与宫颈癌不同分期、分化程度、淋巴结是否转移无关（P〉0.05）。在宫颈癌组中Notch1与HPV16E6/E7的表达均呈正相关性（P〈0.01）。结论 Notch1表达与HPV16E6/E7感染可能与CIN及宫颈癌的发生密切相关,两者在宫颈癌的发病机制中可能协同发挥作用。     

E6/E7 mRNA检测在宫颈癌高危人群HPV分流的应用

目的探讨采用E6/E7 mRNA检测方法对于CIN1及以下病变的宫颈癌高危人群HPV阳性分流的可行性。方法选择2016年1—6月山西省古交市、北京市密云县和河北省曲周县在2014年政府免费宫颈癌筛查中发现的322例诊断为宫颈上皮内病变(CIN1)及以下病变作为研究对象,进行HPV PCR分型检测,其中高危HPV阳性者再进行宫颈细胞学检查和E6/E7 mRNA检测,任一阳性者进行阴道镜检查,并对阴道镜检查可疑或异常者进行定点活检和组织病理学检查。结果 322例患者中,高危型HPV阳性检出率为34.2%(110/322),其中80例(72.7%)为单一HPV高危亚型阳性,主要感染型别前三位分别为HPV52、HPV16和HPV58。宫颈细胞学分流检出CIN2及以上病变2例(1.8%,2/110)。E6/E7 mRNA分流检出CIN2及以上病变5例,检出率为4.6%。在E6/E7 mRNA阳性患者中CIN2及以上为5例(14.3%);E6/E7 mRNA阴性患者中,CIN2及以上患者为3例(4.0%),两组比较,差异无统计学意义(P=0.066)。结论对于HPV阳性者采用E6/E7 mRNA分流宫颈癌前病变的检出率高于细胞学分流,可应用于宫颈癌高危人群HPV阳性的分流。     

HPV E6/E7mRNA原位杂交技术在HPV分型检测阴性的子宫颈腺癌中的研究

目的:探讨人乳头瘤病毒(HPV)分型检测阴性的子宫颈腺癌中HPV E6/E7mRNA的表达情况,为子宫颈腺癌的早期筛查提供新思路。方法:选择2019年1月至2021年6月于潍坊医学院附属医院和山东大学齐鲁医院就诊的HPV分型检测阴性的15例子宫颈腺癌患者为研究组,同期HPV分型检测阳性的15例子宫颈腺癌患者为对照组。采用高危型HPV E6/E7mRNA原位杂交(RISH)检测两组患者病变组织中HPV E6/E7mRNA的表达情况,同时采用免疫组化法(IHC)检测p16和Ki-67的表达情况。结果:与对照组比较,研究组HPV E6/E7 mRNA的阳性表达(73.3%vs.100.0%)、p16的阳性表达(80.0%vs.100.0%)及Ki-67的阳性表达(86.7%vs.100.0%),差异均无统计学意义(P>0.05)。研究组中HPV E6/E7mRNA表达阴性的4例患者病理类型均属于非HPV相关子宫颈腺癌(胃型腺癌2例,微偏腺癌2例),HPV E6/E7mRNA在HPV相关和非HPV相关中的阳性占比分别为100.0%(26/26)和0(0/4);其中1例普通浸润型腺癌HPV...     

APTIMA HPV E6/E7 mRNA和MALDI-TOF-MS HPV基因分型检测宫颈高度病变效果评价

目的:以HC-Ⅱ法HPV DNA为对照,评价APTIMA法HPV E6/E7 mRNA检测(A-HPV)和MALDI-TOF-MS HPV分型检测技术(M-HPV)用于宫颈癌与癌前病变筛查的临床价值。方法:深圳市25~59岁、3年内未行宫颈癌筛查、未接受过子宫切除和盆腔放疗的2095例未孕妇女参加了本次筛查。医生于患者宫颈外口处直接收集2份宫颈脱落细胞标本,一份用于液基细胞学检查,一份用于HC-Ⅱ、A-HPV和M-HPV检测。宫颈细胞学≥ASCUS及3种方法 HPV检测任一阳性结果者均回叫行阴道镜下定点或四象限活检及宫颈管诊刮(ECC)。以病理诊断为标准评价各种HPV检测方法用于宫颈癌筛查的价值。结果:2095例研究对象中各项检测数据齐全者1970例。1970例患者的平均年龄为(35.89±7.655)岁。细胞学≥ASCUS者占6.4%(127/1970),CINⅡ+者占1.3%(26/1970),CINⅢ+者占0.76%(15/1970)。HC-Ⅱ、A-HPV和M-HPV总的HPV阳性率分别是19.4%、12.1%和14.8%,差异有统计学意义(P0.05)。HC-Ⅱ、A-HPV和M-HPV对检出CINⅡ+病变的敏感性分别为88.5%(95%CI为68.7~97.0)、100%(95%CI为84.0~100)和92.3%(95%CI为73.4~98.7),特异性分别为81.5(95%CI为79.7~83.2)、89.1%(95%CI为87.6~90.4)和86.3%(95%CI为84.6~87.8);A-HPV与HC-Ⅱ相比敏感性稍高(P0.05),M-HPV敏感性和HC-Ⅱ相同(P0.05),三者比较有统计学意义(P0.05)。结论:A-HPV和M-HPV用于宫颈癌筛查都有很好的敏感性和准确性,两者活检率明显低于HC-Ⅱ,可减少医疗负担和花费。HPV亚型分型和HPV E6/E7 mRNA结合有更好地预测宫颈癌患病风险的作用。