216例宫颈细胞学为ASCUS的临床意义及处理探讨

目的：探讨宫颈细胞学诊断为意义未明的不典型鳞状细胞（ASCUS）的临床意义及处理方法。方法：2008年1月—2009年12月,对天津医科大学总医院妇科门诊的216例宫颈细胞学诊断为ASCUS的患者行阴道镜评估与镜下活检,其中140例同时接受了人乳头瘤病毒（HPV）检测。结果：①ASCUS患者宫颈上皮内瘤样病变（CIN）的发生率为44.44%,高级别CIN与宫颈癌发生率为20.37%。②高级别CIN及宫颈癌发病平均年龄为（44.57±11.23）岁,明显高于湿疣和低级别CIN者（均P＜0.05）。③发生宫颈高级别CIN及宫颈癌的ASCUS患者高危HPV亚型以16型最常见,出现概率为41.67%,HPV58、18、52型感染率排在第2～4位。④HPV阳性者CIN检出率为55.56%,明显高于HPV阴性者的31.25%和直接阴道镜检的38.16%（均P＜0.05）。⑤HPV检测高度鳞状上皮内病变（HSIL）阴性预测值为93.75%。结论：ASCUS病理类型复杂,32岁以下年轻患者发生宫颈湿疣可能性大,40岁以上特别是合并HPV16、58、18、52型感染者应警惕高级别CIN及宫颈癌的可能。ASCUS患者应先行HPV检测分流,阳性者联合阴道镜检查以提高CIN检出率,阴性者可定期重复细胞学检查。     

216例宫颈细胞学为ASCUS的临床意义及处理探讨

目的：探讨宫颈细胞学诊断为意义未明的不典型鳞状细胞（ASCUS）的临床意义及处理方法。方法：2008年1月—2009年12月,对天津医科大学总医院妇科门诊的216例宫颈细胞学诊断为ASCUS的患者行阴道镜评估与镜下活检,其中140例同时接受了人乳头瘤病毒（HPV）检测。结果：①ASCUS患者宫颈上皮内瘤样病变（CIN）的发生率为44.44%,高级别CIN与宫颈癌发生率为20.37%。②高级别CIN及宫颈癌发病平均年龄为（44.57±11.23）岁,明显高于湿疣和低级别CIN者（均P〈0.05）。③发生宫颈高级别CIN及宫颈癌的ASCUS患者高危HPV亚型以16型最常见,出现概率为41.67%,HPV58、18、52型感染率排在第2～4位。④HPV阳性者CIN检出率为55.56%,明显高于HPV阴性者的31.25%和直接阴道镜检的38.16%（均P〈0.05）。⑤HPV检测高度鳞状上皮内病变（HSIL）阴性预测值为93.75%。结论：ASCUS病理类型复杂,32岁以下年轻患者发生宫颈湿疣可能性大,40岁以上特别是合并HPV16、58、18、52型感染者应警惕高级别CIN及宫颈癌的可能。ASCUS患者应先行HPV检测分流,阳性者联合阴道镜检查以提高CIN检出率,阴性者可定期重复细胞学检查。     

内蒙古镶黄旗地区妇女宫颈病变筛查现状

目的探讨宫颈细胞学(包括巴式涂片及超柏氏薄层液基细胞学)及阴道镜检查筛查内蒙古镶黄旗地区妇女宫颈病变的现状及临床意义。方法2004年7月至2009年1月对内蒙古镶黄旗地区的642例28～67岁有性生活妇女进行宫颈病变筛查,其中557例妇女行传统宫颈巴式涂片法,85例妇女行宫颈超柏氏薄层液基细胞学,并对宫颈细胞学异常者(≥ASCUS)行阴道镜检查及活检。结果642例妇女中宫颈细胞学阳性(≥ASCUS)者34例,占5.3%(34/642),其中ASCUS者22例,占64.7%(22/34);低度鳞状上皮内病变(LSIL)者6例,占17.6%(6/34);高度鳞状上皮内病变(HSIL)者6例,占17.6%(6/34),其中有1例肯定为宫颈癌。宫颈细胞学阴性608例,占94.7%(608/642)。宫颈细胞学阳性34例人群中,行阴道镜活检病理检查者有25例,其中慢性宫颈炎13例(52.0%);CIN1为5例(20.0%);CIN2为4例(16.0%);CIN3为1例(4.0%);浸润癌为2例(8.0%)。结论应重视并及时进行经济不发达地区妇女人群宫颈病变的早期筛查,传统宫颈巴式涂片法及阴道镜活检及病理学检查为可行的筛查方法,有条件者可进行宫颈薄层液基细胞学结合阴道镜活检及病理学检查,对提高早期宫颈癌筛查的准确性效果明显。对内蒙古等西部地区,应在完善技术力量支持、筛查质量控制、建立筛查后的转诊制度及治疗的绿色通道等方面,以降低宫颈癌的发病率。     

醋酸-碘试验在宫颈癌早期筛查中的价值

目的：评价宫颈醋酸－碘试验（VIA-VILI）筛查宫颈癌早期病变的价值。方法：2008年5月—9月对天津市大港区迎新街社区的2 006例30~59岁有性生活妇女进行宫颈癌早期病变筛查。采集宫颈脱落细胞留做薄层液基细胞学（LCT）检测。然后应用5%醋酸及希乐液涂抹法进行VIA-VILI,VIA-VILI阴性而LCT结果异常者、VIA阳性者或VILI阳性者行阴道镜检查及活检病理检查。结果：最终有2 000例纳入试验,VIA-VILI阳性并取活检347例,病理结果显示≥CINⅡ者47例（占13.54%）;LCT阳性并取活检134例,病理结果显示≥CINⅡ的50例（37.31%）,其中39例为VIA-VILI及LCT均为阳性者。筛查CINⅡ及以上宫颈病变和宫颈癌的敏感度、特异度和约登指数,VIA-VILI方法分别为81%、84.6%和0.656,LCT检查分别为90.3%、88.4%和0.787。结论：VIA-VILI试验筛查宫颈病变的效率虽低于LCT检查,但方便快捷、价格低廉,在经济不发达地区或低收入人群中有一定应用价值。     

阴道镜活检782例临床病理分析

目的:了解阴道镜活检和HPV感染在宫颈病变诊断中的价值.方法:分析782例行阴道镜下活组织检查并有病理结果患者的临床病理资料.结果:①782 例共检出宫颈上皮内瘤变293例,包括CTN Ⅰ 139例(17.8%),CIN Ⅱ90例(11.5%),CIN Ⅲ 64例(8.2%);宫颈浸润癌13例(1.7%);子宫内膜癌3例(0.4%);其余为:炎症451例(57.7%)、宫颈湿疣22例(2.8%).②宫颈病理学阳性组(包括CTN和宫颈浸润癌)和病理学阴性组(包括炎症和宫颈湿疣)的HPV阳性率分别为52.0%和40.4%,差异有非常显著性(P＜0.01).③HPV阳性者较HPV阴性者年龄显著降低,差异有非常显著性(P＜0.01).结论:阴道镜检查对CIN和宫颈癌的早期诊断具有重要价值,HPV感染是宫颈癌和CIN的重要原因,HPV阳性者的年龄显著低于HPV阴性者.     

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。     

宫颈巴氏涂片与LCT在低收入妇女妇科普查中的应用

目的探讨宫颈巴氏涂片与液基细胞学（LCT）在低收入已婚妇女宫颈癌筛查中的应用价值。方法2008年1月至6月上海市浦东新区妇幼保健院对所在社区6416例低收入已婚妇女（低收入组）采用宫颈巴氏涂片进行了宫颈癌筛查,其中322例同期行LCT,并与同期来上海市浦东新区妇幼保健院做宫颈癌筛查行LCT的294名妇女进行对照（对照组）。结果①宫颈刮片巴氏异常者（≥Ⅱb级）低收入组中22例（0．34％）,其中Ⅱb级12例（0．19％）,Ⅲ级10例（0．16％）,无Ⅳ级及Ⅴ级。15例（Ⅱb5例,其余Ⅲ级）行阴道镜下活检,病理结果CIN8例,其中CIN12例,CIN2和CIN3各3例;②低收入组同期行LCT的322例妇女中,细胞学≥ASCUS共41／322例（12．73％）,其中ASCUS15例,HSIL 1例,行阴道镜下活检病理结果CIN5例（CIN1和CIN2各2例,CIN31例）;HSIL1例为子宫颈鳞状细胞癌。对照组：细胞学≥ASCUS 22／294例（7．48％）。其中ASCUS 11例行阴道镜下活检。病理结果仅CIN 21例;2例LSIL;1例为CIN2。两组AGC各1例经阴道镜下活检均无异常;③低收入组中322例行宫颈刮片和LCT做自身对照：315例巴氏均为Ⅰ级,LCT正常;巴氏Ⅱb级2例,LCT均为ASCUS,病理分别为CIN1和CIN2;巴氏Ⅲ级3例,LCT检查,其中2例为ASCUS,阴道镜活检仅1例病理为CIN2。结论宫颈细胞学是筛查宫颈病变的有效手段,巴氏涂片法在基层对低收入人群仍可为主要筛查方法。有条件者可采用LCT,以提高宫颈疾病筛查的敏感性。     

阴道镜检查在宫颈细胞学ASCUS分流管理中的应用

目的探讨电子阴道镜检查在宫颈细胞学意义未明的不典型鳞状细胞(atypical squamous cell of undeter-mined significance,ASCUS)分流管理中的临床应用价值。方法对2006年7月至2008年7月在天津医科大学第二医院门诊行宫颈液基细胞学检查(TCT)结果为ASCUS的471例患者进行电子阴道镜检查,其中203例阴道镜诊断为宫颈上皮内瘤变(cervical intraepithelial neoplasia,CIN)及以上病变者在可疑病变区取活检送病理检查;268例阴道镜检查为正常或慢性宫颈炎者给予阴道用药治疗1~3个疗程,3个月后复查宫颈涂片,4例细胞学仍异常者行阴道镜下取活检送病理检查,余264例细胞学阴性者定期复查宫颈细胞学。结果471例宫颈细胞学AS-CUS患者中,共行活体组织病理学检查207例(43.95%),检出宫颈上皮内瘤样病变(CINⅠ~Ⅲ)131例,宫颈癌4例,余264例避免了宫颈活检损伤,随访6~30个月复查宫颈细胞学均未发现异常。结论电子阴道镜结合宫颈细胞学检查可有效检出宫颈细胞学ASCUS中CIN及宫颈癌患者,可作为基层医院对ASCUS进行有...     

醋白肉眼观察试验在宫颈病变筛查中的价值

目的以宫颈细胞学、阴道镜检查及活检的诊断结果为标准，评价宫颈醋白肉眼观察试验（vision inspection with acetic acid，VIA）在宫颈病变筛查中的价值。方法2006年6月～7月对北京市展览路社区的790位20～54岁有性生活妇女进行宫颈病变筛查。采取每名妇女的宫颈脱落细胞，留做薄层液基细胞学（LCT）检测，然后应用5％醋酸涂抹法，进行宫颈醋白肉眼观察试验（VIA），VIA阳性者行阴道镜检查及活检病理检查；VIA阴性者若宫颈细胞学检测结果异常，再行阴道镜检查及活检病理检查。结果最终有783人纳入试验诊断效果评价分析，总共取了71例活检，病理组织学检查结果显示，宫颈早期浸润癌1例，CINⅢ4例，CINⅡ3例，CINⅠ12例。VIA方法筛查CINⅡ及以上宫颈病变和宫颈癌的灵敏度为62．5％，特异度为95．9％，阳性预测值为13．5％，阴性预测值为99．6％。结论醋白肉眼观察试验筛查宫颈病变的效率接近传统巴氏涂片，但因其方便快捷、价格低廉，在经济不发达地区或低收入人群中有一定应用价值，但是需要注意漏诊和过度治疗问题。     

2341例妊娠妇女宫颈筛查及产后随访

目的:分析孕期妇女宫颈细胞学检查、HPV检测、活检组织病理结果及产后自然转归状况。方法:选择2009年1月～2010年2月在北京大学人民医院接受孕期产检及分娩病例,孕前半年未行液基细胞学(TCT)检测,孕早期或中期均进行TCT检查,结果异常者部分行人乳头瘤病毒杂交捕获Ⅱ代(HPVHC-Ⅱ)法检测,阴道镜检查及病理学检查。结果:(1)2341例孕妇中宫颈细胞学意义不明的非典型鳞状上皮细胞(ASCUS)及以上患者60例(2.56%),其中高度鳞状上皮内病变(HSIL)8例(0.34%),低度鳞状上皮内病变(LSIL)4例(0.17%),ASCUS48例(2.05%);细胞学异常者中25例行HPV检测,阳性18例(72%);细胞学异常者28例接受阴道镜检查,病理活检者21例;病理学结果宫颈上皮内瘤变(CIN)共13例(0.56%):CINⅠ3例(0.13%);CINⅡ2例(0.085%),CINⅢ8例(0.34%);(2)产后随访了51例,细胞学正常/炎症41例(细胞学转阴率80.4%),ASCUS8例,LSIL1例,ASC-H1例。孕期HPV阳性者,13例产后复查,4例仍为阳性,孕期与产后比较有显著性差异(P=0.004)。孕期CIN11例中,产后仍为CIN6例(CINⅠ1例、CINⅡ1例、CINⅢ4例),无早期浸润癌发生。结论:(1)妊娠期宫颈细胞学异常在产后有较高的转阴率,同时妊娠期存在较高的HPV亚临床感染,产后转阴率高;(2)妊娠期CIN患者在密切随访下继续妊娠是安全的;(3)妊娠期CIN患者产后应密切随访,若产后仍为CIN应尽快治疗。     

改良取样巴氏涂片在人群子宫颈癌筛查中的应用

目的：探讨改良取样巴氏涂片（Pap）在子宫颈癌筛查中的应用价值。方法：对500例30~59岁、3年内未行宫颈癌筛查的妇女行改良Pap、液基细胞学（LCT）和第二代杂交捕获实验（HC-Ⅱ）人乳头瘤病毒（HPV）检测,Pap采用液基细胞学刷取样,2种细胞学取样采用分配样本法。细胞学以无明确诊断意义不典型鳞状细胞（ASCUS）为阳性阈值,对任一细胞学结果或HPV检测阳性的妇女行阴道镜下宫颈多点活检,以病理诊断为金标准,评价2种细胞学方法筛查宫颈癌的价值。结果：宫颈细胞学筛查宫颈上皮内瘤样病变（CIN）Ⅱ以上病变以ASCUS为阳性阈值的筛查效率最高;改良Pap和LCT的筛查效率（ROC曲线下面积比较,Z ＝0.70,P ＞0.05）和不满意率（χ2＝0.343,P =0.558）差异无统计学意义;两种细胞学的诊断完全一致率为86.8%,宫颈癌和宫颈癌前病变级别越高,2种细胞学方法判读结果的一致性越好。结论：改良Pap经济有效,可广泛应用于人群子宫颈癌筛查。     

改良取样巴氏涂片在人群子宫颈癌筛查中的应用

目的：探讨改良取样巴氏涂片（Pap）在子宫颈癌筛查中的应用价值。方法：对500例30-59岁、3年内未行宫颈癌筛查的妇女行改良Pap、液基细胞学（LCT）和第二代杂交捕获实验（HC-II）人乳头瘤病毒（HPV）检测,Pap采用液基细胞学刷取样,2种细胞学取样采用分配样本法。细胞学以无明确诊断意义不典型鳞状细胞（ASCUS）为阳性阈值,对任一细胞学结果或HPV检测阳性的妇女行阴道镜下宫颈多点活检,以病理诊断为金标准,评价2种细胞学方法筛查宫颈癌的价值。结果：宫颈细胞学筛查宫颈上皮内瘤样病变（CIN）Ⅱ以上病变以ASCUS为阳性阈值的筛查效率最高;改良Pap和LCT的筛查效率（ROC曲线下面积比较,Z=0．70,P〉0．05）和不满意率（χ2=0．343,P=0．558）差异无统计学意义;两种细胞学的诊断完全一致率为86．8％,宫颈癌和宫颈癌前病变级别越高,2种细胞学方法判读结果的一致性越好。结论：改良Pap经济有效,可广泛应用于人群子宫颈癌筛查。     

Risk of precancer and follow-up management strategies for women with human papillomavirus-negative atypical squamous cells of undetermined significance

OBJECTIVE: To investigate the relative performances of follow-up cytology and carcinogenic human papillomavirus (HPV) DNA testing among carcinogenic HPV-negative women with atypical squamous cells of undetermined significance (ASCUS), for detection of cervical precancer. METHODS: Twelve-month follow-up management strategies to detect cervical intraepithelial neoplasia grade 3 (CIN3) or worse using cytology or HPV testing or both were compared among women with HPV-negative ASCUS in the Atypical Squamous Cells of Undetermined Significance-Low-Grade Squamous Intraepithelial Lesion (ASCUS-LSIL) Triage Study. RESULTS: Overall only 22 of 1,559 (1.4%) HPV-negative ASCUS women developed CIN grade 3 or worse during follow-up compared with 269 of 1,767 (15.2%) HPV-positive ASCUS women (P<.001). Because of the low risk of disease among HPV-negative ASCUS women, only 7 cases of CIN3 were diagnosed between 12 and 24 months of follow-up, limiting power to distinguish meaningful differences in sensitivity among 12-month testing strategies. The specificity of HPV testing (84%) was significantly higher than cytology using an ASCUS threshold (71%) (P<.001). Cotesting with cytology and HPV testing at 12 months resulted in even lower specificity (61%). Because cases were uncommon, the positive predictive value for subsequent CIN3 or worse was low for cytology (2.6%), Hybrid Capture 2 (3.8%), and cotesting with cytology and HPV testing (2.2%). The negative predictive value for all three management strategies was very high (99.70%, 99.82%, and 100.0% for HPV testing, cytology, or cotesting, respectively.) CONCLUSION: Women with HPV-negative ASCUS have very low absolute risk of subsequently detected CIN3 or worse in the subsequent 2 years, similar to women with a negative cytology in the absence of HPV testing. The results suggest that women with HPV-negative ASCUS should return to routine screening intervals which may be longer than 1 year depending on age and screening history. However, if increased surveillance is chosen, a single HPV test for carcinogenic types at 12 months has significantly higher specificity and lower referrals than cytology.     

Expanded cytological referral criteria for colposcopy in cervical screening: comparison with human papillomavirus testing

OBJECTIVE: The goal of this study was to investigate whether expanded cytologic referral criteria for colposcopy or the addition of human papillomavirus (HPV) testing on cervical screening could improve the rates of detection of cervical intraepithelial neoplasia (CIN). METHODS: HPV testing by semiquantitative polymerase chain reaction/ELISA was performed in 1000 women who were self-referred for routine Pap smear. They underwent colposcopy following an abnormal smear result or a positive HPV test. As abnormal smear results were considered reports of low- or high-grade squamous intraepithelial lesion, atypical squamous cells of undetermined significance, and even HPV-associated reactive cellular changes (mild koilocytosis, mild dyskeratocytosis, hyperchromatic nuclei, bimultinucleation, and cleared cytoplasm). Loop excision of the transformation zone was performed in women with cytology and colposcopy indicative of CIN, as well as in women with normal cytology but positive HPV test and colposcopic impression of CIN. RESULTS: The Pap test was abnormal in 89% of the cases of CIN 1 (34/38) and 96% of CIN 2/3 (27/28) diagnosed in our population. HPV testing picked up four additional cases of CIN 1 (11%) and one case of CIN 2/3 (4%). Overall the HPV test detected 95% of the cases of CIN 1 (36/38) and 89% of the cases of CIN 2/3 (25/28). CONCLUSION: HPV testing does not appear to add significantly to cytology in terms of positive predictive value or detection rate, if extended cytologic indications for colposcopy are used.     

Triaging Pap cytology negative, HPV positive cervical cancer screening results with p16/Ki-67 Dual-stained cytology

Objective

Testing for human papillomavirus (HPV) has been shown to increase the sensitivity and negative predictive value for detection of high-grade cervical intraepithelial neoplasia (CIN2+), either when used in conjunction with Pap cytology testing or alone. However, there is no satisfying clinical management algorithm for women testing Pap negative/HPV positive. We therefore evaluated the clinical utility of a novel dual biomarker-based approach (p16/Ki-67 Dual-stained cytology) for the identification of CIN2+ in women with Pap negative/HPV positive screening results, without the need to refer all women to immediate colposcopy.

Methods

All women aged ≥ 30 enrolled during 2007/2008 into a regional prospective Pap/HPV co-testing screening pilot project and tested Pap negative, but positive for HPV (n = 425) were included in the analysis. p16/Ki-67 Dual-stained cytology was performed from residual cellular material available from the liquid-based cytology vial collected during the initial Pap/HPV co-testing screening visit. Results were correlated to the presence of CIN2+ confirmed during preliminary follow-up.

Results

p16/Ki-67 Dual-stained cytology tested positive at baseline in 108 out of 425 (25.4%) Pap negative/HPV positive cases. Sensitivity of Dual-stain testing for the detection of biopsy-confirmed CIN2+ during preliminary follow-up within the group of Pap negative/HPV positive women was 91.9% for CIN2+ (34/37 cases), and 96.4% for CIN3+ (27/28 cases). Specificity was 82.1% for CIN2+ on biopsy, and 76.9% for CIN3+, respectively.

Conclusions

Triaging Pap negative/HPV positive screening test results with p16/Ki-67 Dual-stained cytology may identify women with a high probability of underlying CIN2+ and may efficiently complement HPV-based screening programs to prevent cervical cancer.     

Human papilloma virus testing in patient follow-up post cone biopsy due to high-grade cervical intraepithelial neoplasia

OBJECTIVE: We evaluated the contribution of the human papilloma virus (HPV) load in planning follow-up and management of women post cone biopsy for high-grade cervical intraepithelial neoplasia (CIN2-3). METHODS: Ninety-six suitable women were followed-up by Pap smears: two consecutive abnormal smears dictated referral for colposcopy-directed biopsy. Before colposcopy, HPV tests determined high-risk HPV DNA type and load (Hybrid Capture System type I). Patients histologically diagnosed with CIN1 or CIN2-3 underwent repeat conization or hysterectomy for residual disease. HPV load was compared to cytology for the detection of residual disease. RESULTS: At follow-up, 20/89 (22.4%) studied women had positive cytology reports of either low- (n = 11) or high-grade (n = 9) squamous intraepithelial lesion (SIL). Colposcopic biopsies diagnosed 9 CIN1 and 8 CIN2-3 cases. Residual disease was corroborated in 16/17 (94.1%) women and the status was readjusted based on cone biopsy/hysterectomy: CIN2-3 in 9 and CIN1 in 7. The positive prediction values for CIN2-3 residual disease with high-grade SIL, CIN2-3 on colposcopic punch biopsy, and high HPV load were 89, 100, and 100%, respectively. For CIN1 residual disease with low-grade SIL, CIN1 on colposcopic punch biopsy, and low and borderline HPV load, they were 54.5, 77.7, and 100%. The HPV load was a more accurate predictor for CIN1 or CIN2-3 on the cervical specimen in cases with low-grade SIL or CIN1 on colposcopic biopsy. CONCLUSIONS: Evaluating HPV loads after a positive cytology report may assist in triaging women post conization biopsy for CIN2-3 to appropriate treatment. Its high positive predictive value, specificity, and sensitivity for CIN1 and CIN2-3 and supplementary information could be especially pertinent for clinical management of low-grade SIL cases.     

Follow-up by combined cytology and human papillomavirus testing for patients post-cone biopsy: results of a long-term follow-up

OBJECTIVE: The goal of this study was to evaluate the clinical implications of integrating human papillomavirus (HPV) testing into a long-term follow-up and management protocol for women postconization for high-grade cervical intraepithelial neoplasia (CIN2-3). METHODS: Sixty-seven women were followed-up by Pap smears and HPV type and load testing (mean follow-up, 63 months; range, 50-72). Patients with persistent abnormal cytology on two consecutive smears and those with positive HPV test results (whatever their cytologic findings) were referred for colposcopy-directed biopsy. Patients histologically diagnosed with CIN2-3 and those with high-load HPV (whatever their histologic findings) underwent repeat conization or hysterectomy for residual disease. RESULTS: At follow-up, 29 (43.2%) women had positive cytology or positive HPV results and were referred for colposcopy. Eleven (37.9%) had high-grade cervical intraepithelial neoplasia or high-load HPV results and were further treated by reconization/hysterectomy. The respective positive predictive values of high-load HPV and low-grade squamous intraepithelial lesions were 100 and 60% for any CIN and 90 and 15% for CIN2-3. Only five of nine cases with a final diagnosis of CIN2-3 were originally identified by cytology: the other four were detected only by parallel evaluation by HPV testing. High-load HPV results with normal cytology or low-grade lesions harbored an 80% risk for CIN2-3. CONCLUSIONS: Adding HPV load assessment to the follow-up protocol of women postconization due to CIN2-3 lesions could help detect high-grade residual disease among low-grade lesions and normal cytology cases while concomitantly and safely bestowing the advantage of lowering the rates of colposcopic referrals and surgical procedures.     

The current status of HPV DNA testing

Infection with high-risk types of HPV underlies most cases of high-grade cervical intraepithelial neoplasia (CIN) and practically all cases of invasive cervical cancer. Currently, cervical HPV DNA is detected by means of PCR and sandwich capture molecular hybridization methods. Research has focused on the potential role of HPV testing in three conditions: screening for cervical neoplasia, triage of women with low-grade lesions and follow-up after conservative surgical treatment for CIN. Concerning the first condition, HPV testing does not seem to offer an obvious advantage over traditional cytology screening, mainly due to false positive results in younger women with transient HPV infection. A possible exemption to this is the case of middle-aged women and low-resource settings, where the excellent sensitivity of a HPV test is desirable. Although data are controversial regarding low grade lesions, results from randomized studies indicate that HPV testing could be useful in a triage of women with an initial cytological diagnosis of ASCUS, where detection of DNA of a high-risk type should lead to colposcopy. Although there is a lack of randomized controlled trials in this field, data from observational studies indicate that HPV DNA testing after conservative surgical treatment for CIN may be very sensitive and detect early residual and recurrent disease.