Type‐dependent association between risk of cervical intraepithelial neoplasia and viral load of oncogenic human papillomavirus types other than types 16 and 18

Studies of the clinical relevance of human papillomavirus (HPV) DNA load have focused mainly on HPV16 and HPV18. Data on other oncogenic types are rare. Study subjects were women enrolled in the atypical squamous cells of undetermined significance (ASC‐US) and low‐grade squamous intraepithelial lesion (LSIL) triage study who had ≥1 of 11 non‐HPV16/18 oncogenic types detected during a 2‐year follow‐up at 6‐month intervals. Viral load measurements were performed on the first type‐specific HPV‐positive specimens. The association of cervical intraepithelial neoplasia grades 2–3 (CIN2/3) with type‐specific HPV DNA load was assessed with discrete‐time Cox regression. Overall, the increase in the cumulative risk of CIN2/3 per 1 unit increase in log₁₀‐transformed viral load was statistically significant for four types within species 9 including HPV31 (adjusted hazard ratio [HR _adjusted] = 1.32: 95% confidence interval [CI], 1.14–1.52), HPV35 (HR _adjusted = 1.47; 95% CI, 1.23–1.76), HPV52 (HR _adjusted = 1.14; 95% CI, 1.01–1.30) and HPV58 (HR _adjusted = 1.49; 95% CI, 1.23–1.82). The association was marginally significant for HPV33 (species 9) and HPV45 (species 7) and was not appreciable for other types. The per 1 log₁₀‐unit increase in viral load of a group of species 9 non‐HPV16 oncogenic types was statistically significantly associated with risk of CIN2/3 for women with a cytologic diagnosis of within normal limits, ASC‐US, or LSIL at the first HPV‐positive visit but not for those with high‐grade SIL. Findings suggest that the viral load‐associated risk of CIN2/3 is type‐dependent, and mainly restricted to the species of HPV types related to HPV16, which shares this association.     

Prevalence and type distribution of human papillomavirus in squamous cell carcinoma and intraepithelial neoplasia of the vulva

In this updated systematic review and meta‐analysis, we estimate the pooled prevalence of human papillomavirus (HPV) DNA and HPV type distribution in squamous cell carcinoma of the vulva (vulvar cancer) and vulvar intraepithelial neoplasia (VIN). PubMed, Embase and Cochrane Library databases were used to identify studies published between 1990 and 2015 and using a PCR‐based or hybrid capture test to evaluate the presence of HPV DNA in vulvar cancer or VIN. Pooled estimates of the HPV prevalence with corresponding 95% confidence intervals (CI) were calculated based on a random effects model. The I² statistic was used to describe the amount of heterogeneity. In meta‐regression analyses, potential sources of heterogeneity were evaluated. We identified 92 eligible papers, comprising altogether 5,015 cases of vulvar cancer (64 papers) and 2,764 cases of VIN (48 papers). The pooled prevalence of HPV in vulvar cancer was 39.7% (95% CI: 35.1–44.4%). Overall, 76.3% (95% CI: 70.1–82.1%) of VIN lesions tested HPV‐positive, while the HPV prevalence in new subcategories of VIN, uVIN and dVIN, was 86.2% (95% CI: 73.5–95.5%) and 2.0% (95% CI: 0–10.0%), respectively. Substantial between‐study heterogeneity was observed (vulvar cancer: I² = 88.4%; VIN: I² = 90.7%) with the largest variation between geographical regions. Among HPV‐positive cases, the predominant high‐risk HPV type was HPV16, followed by HPV33 and HPV18. HPV6 was detected as a single infection in a small subset of VIN and vulvar cancer samples. Thus, HPV vaccination targeting these HPV types may prevent a substantial number of vulvar lesions.     

Bacterial Vaginosis and Cervical Intraepithelial Neoplasia: Is there an Association or is Co-Existence Incidental?

Objectives: To determine associations, if any, of bacterial vaginosis with cervical pre-neoplastic lesions and evaluate any effects of sub-categorization of smears with bacterial vaginosis. Methods: All cervico-vaginal smears reported as positive for bacterial vaginosis over a five-year period were reviewed and sub-categorized into ‘type I (dysbacteriosis)’ and ‘type II (pure Gardenerella infection)’ smears by two cytopathologists (PS, SG). The proportion of smears with healthy flora and pre-neoplastic lesions was compared with those having bacterial vaginosis in conjunction with such changes. In addition, a comparison was also attempted between the frequencies of pre-neoplastic lesions with the two categories of bacterial vaginosis smears. Results: Bacterial vaginosis was diagnosed in 28.6% (7017 of the 24,565) of the 24,565 smears received in the Institute during the study period. Of these 7,017 smears with bacterial vaginosis, 53% (3717) were categorized as type I and 42.7% (3000) as type II by both cytopathologists. Pre-neoplastic lesions were detected in 10.2% of smears with bacterial vaginosis compared to 5.7% of those with healthy flora (P<0.0001). Of the sub-categories of bacterial vaginosis, the risk of detecting precancerous lesion was higher for type II smears (P<0.001). Conclusion: Sub-categorization of bacterial vaginosis, as performed in the Dutch coding system, may be worthwhile due to the strikingly different risk of associated preneoplasia.     

Flow Cytometric Analysis of DNA Ploidy in Liquid Based Cytology for Cervical Pre-Cancer and Cancer

Background: DNA ploidy analysis of cervical intraepithelial neoplasia (CIN) and invasive cervical cancer samples by flow cytometry (FCM) has been established as an aid to prognostic assessment. Liquid based cytology (LBC) increases diagnostic specificity by using ancillary techniques that provide information beyond morphology. The present study was undertaken to assess DNA ploidy in LBC samples as an adjunct for early detection of cervical pre-cancer and cancer. Methods: DNA ploidy assessment was performed on LBC samples of 50 cases and 31 controls. Cell pellets were obtained by centrifugation and stained with Telford reagent. At least 20,000 R1 gate (G0-G1) events were acquired on a BD FACSCalibur by using a 575±10 nm filter. Results: Mean diploid G1 values were lowered significantly (p<0.01) while diploid S values were significantly elevated (p<0.01) in both high grade squamous intraepithelial lesions (HSILs) and squamous cell carcinomas (SCCs) as compared to controls. Receiver operating curve (ROC) analysis of the diploid G1 value was found to have significant diagnostic potential (AUC=0.682, Z=2.00, p=0.046) for distinction between control and low grade squamous intraepithelial lesion (LSIL) at a cut off value of ≤91.6 with a sensitivity and specificity of 50.0 and 87.1%, respectively. Conclusions: ROC analysis of diploid G1 and diploid S values allows discrimination between LSIL and HSIL with sensitivities and specificities of 65 and 100% and 70 and100%, respectively, and between LSIL and SCC cases with values of 71.4 and 100% and 64.3 and 100%, respectively.     

HPV基因分型检测在宫颈高级别病变治疗后的应用进展

高危型人乳头瘤病毒(high risk human papillomavirus,HR-HPV)持续性感染是宫颈上皮内瘤变(cervical intraepithelial neoplasia,CIN)和宫颈癌发生的主要原因。宫颈高级别病变患者在标准治疗后疾病进展风险仍高于正常人群。治疗后HR-HPV阳性、细胞学异常、切缘阳性等是宫颈高级别病变残留/复发的预测因子。HPV基因分型检测能明确治疗后HR-HPV的不同感染状态,有助于检出高风险人群。相较治疗后HR-HPV新发感染和再发感染,同一亚型HR-HPV持续感染与宫颈高级别病变治疗后的疾病残留/复发密切相关。HPV16/18型是宫颈高级别病变患者治疗后最常见的持续感染型别,有更高的疾病残留/复发风险,临床上应加强随访力度。与单纯细胞学、HR-HPV检测相比,随访HR-HPV基因分型能提高预测宫颈高级别病变治疗后疾病残留/复发的敏感度,同时保持相似甚至更高的特异度。     

Are different methotrexate regimens as first line therapy for low risk gestational trophoblastic neoplasia more cost effective than the dactinomycin regimen used in GOG 0174?

Objectives

Gynecologic Oncology Group (GOG) 0174 compared weekly intramuscular methotrexate (MTX) with biweekly pulsed intravenous dactinomycin (Act-D) as single-agent chemotherapy for low-risk gestational trophoblastic neoplasia (GTN). Act-D had a higher rate of initial complete response (CR) (70% vs. 53%, p = 0.01), but multi-day regimens of MTX have higher historic success rates. We assessed the cost-effectiveness of Act-D vs. MTX per GOG 0174 and explored multi-day MTX regimens.

低级别宫颈上皮内瘤变LEEP锥切术与期待治疗的效果观察

目的:比较LEEP锥切术和药物期待治疗低级别宫颈上皮内瘤变的临床效果,分析病变进展危险因素,探讨CINⅠ的最佳治疗方式,防止病情进展。方法:选取160例CINⅠ患者随机分为观察组和对照组,观察组采用LEEP锥切术治疗,对照组采用药物期待治疗,比较两组病变转归及HR-HPV阳性转阴情况,分析病情进展危险因素。结果:观察组进展率为2.4%(2/82),持续率8.5%(7/82),逆转率89.1%(73/82);对照组进展率2.6%(2/78),持续率12.8%(10/78),逆转率84.6%(66/78),两组逆转率差异有统计学意义(P0.05);观察组随访期间HR-HPV持续阳性38.0%(19/50),转阴率62.0%(31/50);对照组HR-HPV持续阳性30.2%(13/40),转阴69.8%(30/40),两组差异无统计学意义(P0.05);持续HR-HPV阳性是CINⅠ病变转归独立危险因素。结论:采用期待治疗低级别宫颈上皮内瘤变安全有效,对于持续HR-HPV阳性患者应密切随访观察,防止病变进展。     

宫颈锥切术后切缘呈阳性的临床处理建议

宫颈锥切术是目前治疗宫颈上皮内瘤变(CIN)Ⅱ～Ⅲ的标准术式。许多研究证实,宫颈锥切术后切缘呈阳性与术后病变残留及宫颈病变复发相关。但是,对于宫颈锥切术后切缘呈阳性应如何处理,目前专家意见尚未达成一致。笔者拟总结国内外专家学者对于宫颈锥切术后切缘呈阳性的临床处理原则及治疗方法,旨在为临床医师对宫颈锥切术后切缘呈阳性的治疗提供参考。     

宫颈细胞学阴性且高危型人乳头瘤病毒阳性人群的分流方法

目的 分析宫颈细胞学阴性且高危型人乳头瘤病毒(HPV)阳性患者的宫颈活检病理结果,探讨Cervista HPV HR A9组病毒应用于此类人群分流的可行性。 方法 对1 376例于2011年1月至2016年1月健康查体的女性行新柏氏液基细胞学检测(TCT)和Cervista HPV HR检测,Cervista HPV HR检测结果分为A5/6、A7、A9组,将TCT阴性、HPV阳性患者转诊阴道镜检查,必要时行镜下宫颈活检术,分析A9组病毒感染与宫颈高级别上皮内瘤变CINII⁺(CINII及CINIII)的关系。 结果 A5/6组、A7组及A9组阳性者分别占28.41%、21.51%、50.07%。A5/A6组、A7组及A9组中CINII⁺的发生率分别为1.28%、3.38%、15.82%,A9组中CINII⁺的发生率明显高于另外两组,其差异具有统计学意义(P<0.001, P<0.001)。A9组病毒感染者发生CINII⁺的风险是A5/A6组感染者的12.37倍,是A7组感染者的4.68倍。 结论 Cervista HPV HR A9组病毒可用于TCT阴性、高危型HPV阳性者的分流。     

液基细胞学配合阴道镜检查诊断宫颈病变

目的探讨液基薄层细胞学（TCT）配合阴道镜检查对子宫颈病变的诊断价值。方法TCT配合阴道镜检查对子宫颈病变进行筛查,以组织学诊断为金标准,对结果进行分析。结果TCT检查2238例,采用TBS分类,共检出阳性涂片201例,占8．98％。其中不典型鳞状上皮细胞（ASC）99例（4．42％）;不典型腺细胞（AGC）4例（0．18％）;低度鳞状上皮内病变（LSIL）63例（2．82％）;高度鳞状上皮内病变（HSIL）28例（1．25％）;鳞状细胞癌（SCC）6例（0．27％）;腺癌（AC）1例（0．045％）。对细胞学阳性（包括ASC及以上病变）或细胞学虽阴性但临床高度可疑者共298例行阴道镜检查,其中251例行镜下活组织病理检查。细胞学与阴道镜下活组织病理诊断符合率分别为LSIL 72．41％（63／87）,HSIL 90．32％（CIN2为15／17,CIN3为13／14）,SCC 100％（6／6）,HPV感染符合率71．11％（32／45）。结论采用TCT筛查,可提高宫颈病变的阳性诊断率;细胞学阳性或临床可疑患者应配合阴道镜检查及镜下活检病理诊断,便于进一步明确诊断,及早治疗。