P16INK4A在宫颈上皮内瘤变中的表达及与HPV感染的关系

目的 探讨抑癌基因P16INK4A在宫颈上皮内瘤变中的表达情况及其与HPV感染的相关性.方法 采用免疫组化染色法,对59例宫颈上皮瘤变(CIN)标本、30例病理检查为正常宫颈组织的标本进行检测.结果 CIN Ⅰ级组织中ILK表达阳性率62.50％、CIN Ⅱ～Ⅲ级为65.71％,均显著高于正常宫颈组织(23.33％),且差异均具有统计学意义(x2=8.472,P=0.004＜0.05;x2=11.675,P=0.001 ＜0.05);CIN Ⅰ级组织中ILK表达阳性率与CIN Ⅱ～Ⅲ级比较差异无统计学意义(x2=0.064,P =0.800 ＞0.05).P16INK4A在HPV16、HPV18 2种高危型宫颈HPV感染中的表达显著高于其他高危型或者低危型(HPV53、HPV58、HPV6).结论 P16INK4A在宫颈上皮内瘤变(CIN)中显著高表达,同时P16INK4A高表达可能与HPV16、HPV18的阳性表达具有协同作用.     

p16INK4A 和bcl-2 蛋白在CIN 和宫颈鳞癌中的表达

 目的 探讨p16INK4A和bcl-2在宫颈上皮内瘤（CIN）和宫颈鳞癌的表达状态及其在病理诊断中的意义。方法 采用免疫组化SP法对39例CIN、24例浸润性宫颈鳞癌和20例正常官颈组织进行p16INK4A和bck2检测。结果 正常宫颈组织不表达p16INK4A，CINⅠ阳性表达率很低并为局灶表达，但几乎所有的CINⅡ／Ⅲ和浸润性宫颈鳞癌均弥漫大量表达p16INK4A。正常宫颈组织只有基底细胞层表达bcl-2蛋白，CINⅢ和Ⅰ～Ⅱ期浸润癌bcl-2阳性细胞弥漫分布，阳性袁达率分别为53．8％和57．1％。Ⅲ～Ⅳ期浸润癌bcl-2阳性率下降，阳性细胞局限。结论 p16INK4A过表达与宫颈鳞癌恶性特性密切相关，检测p16INK4A有助于及时发现高级别CIN和宫颈鳞癌。     

宫颈癌前病变患者治疗前后HPV病毒负荷量变化的临床分析

目的:探讨宫颈癌前病变即宫颈上皮内瘤变(cervicalintraepithelialneoplasia,CIN)患者治疗前后宫颈脱落细胞人乳头瘤病毒(hu-manpapillomavirus,HPV)负荷量的变化。方法:回顾性分析2003年6月1日~2004年12月31日江西省妇幼保健院肿瘤科收治的106例CIN患者的临床资料,分别选择宫颈电圈环切术(loopelectrosurgicalexcisionprocedure,LEEP)与宫颈冷刀锥切术,采用杂交捕获第二代(HybridCapture-Ⅱ,HC-Ⅱ)技术,对纳入研究的患者手术治疗前及术后复查时均行宫颈脱落细胞HPV-DNA检测,观察其治疗前后HPV-DNA负荷量的变化。结果:106例CIN患者中,51例行宫颈LEEP术,55例行宫颈锥切术。行LEEP术患者治疗前后HPV平均负荷量分别为319·7和16·2,行宫颈锥切术患者治疗前后HPV平均负荷量分别为336·1和13·9,CIN患者行宫颈LEEP术和宫颈锥切术治疗后HPV平均负荷量较治疗前均显著降低,P<0·01。宫颈LEEP术与宫颈冷刀锥切术患者治疗后HPV转阴率分别为84·31%和85·45%,CIN患者行宫颈LEEP术和宫颈锥切术治疗后HPV-DNA的转阴率差异无统计学意义,P>0·05。结论:HPV-DNA检测可作为一种有效的判断CIN疗效及随访观察的预后指标。     

高危型HPV负荷量与宫颈上皮内瘤样变级别、Ki-67和P16ink4a表达的关系及随访观察

背景与目的:高危型人乳头瘤病毒(human papillomavirus,HPV)感染是宫颈癌的主要致病原因。HPV负荷量与宫颈癌的关系存在争论,其与肿瘤标记物的关系研究很少。本研究旨在初步探讨高危型HPV负荷量与宫颈上皮内瘤样变(cervical intraepithelial neoplasia,CIN)级别、Ki-67和p16ink4a表达及术后再次出现细胞学异常之间的关系。方法:选择61例CIN患者宫颈组织石蜡标本(CINⅠ8例、CINⅡ12例、CINⅢ41例),免疫组化检测Ki-67、p16ink4a表达。所有患者术前均用第二代杂交捕获法(hybridcaptureⅡ,HCⅡ)检测HPV负荷量,术后进行随访。结果:高危型HPV负荷量与CIN等级、Ki-67和p16ink4a表达之间呈等级正相关(r分别为0.288、0.318、0.336,P<0.05)。经过平均18.5个月的随访,发现6例患者再次出现宫颈脱落细胞学异常,其中5例术前HPV负荷量≥100RLU/PC、<1000RLU/PC,1例≥1000RLU/PC,但术前HPV负荷量与术后再次出现细胞学异常无关(P>0.05)。年龄、产次、组织学诊断、Ki-67与p16ink4a表达强度亦与术后细胞学异常无关。结论:HPV负荷量与CIN进展、细胞恶性程度增高呈正相关。尽管HPV负荷量与术后再次出现细胞学异常无关,但对病毒负荷量>100RLU/PC的患者仍应严密随访。     

人乳头状瘤病毒感染、P16INK4A及PCNA在宫颈上皮内瘤变中的意义

目的探讨人乳头状瘤病毒（HPV）感染及P16INK4A、PCNA在宫颈上皮内瘤变（CIN）中的表达及临床病理意义。方法采用免疫病理组织化EnVision法检测506例宫颈病变中P16INK4A及PCNA的表达情况。通过原位杂交（ISH）检测其HPV16／18型及6／11型DNA的感染率。结果HPV在不同程度宫颈病变中总检出率为47．23％（239／506）,CIN组中检出最多的感染类型为HPV16／18,43．28％（219／506）。CINⅠ级HPV16／18型检出率较鳞化伴增生组明显增加（P〈0．05）;尤其在CINⅡ、CINⅢ组中阳性表达率较高;P16INK4A表达率为72．92％（369／506）,其中CINI级P16INK4A蛋白表达率71．54％（93／130）较宫颈上皮鳞化伴增生组表达率31．96％（31／97）和尖锐湿疣组表达率41.67％（10／24）明显增加（P〈0．01）,CINU组P16INK4A蛋白表达率90．38％（94／104）、CINⅢ组表达率92．6％（112／121）较CINⅠ明显增加（P〈0．01）。PCNA阳性表达率在CINⅠ组、CINⅡ组、CINⅢ、宫颈癌组均不同程度的表达,较宫颈上皮鳞化伴增生组表达率5．15％（5／97）和尖锐湿疣组表达率25．00％（6／18）明显增加（P〈0．01）。结论随宫颈病变严重程度的增加,P16INK4A、PCNA阳性表达率及染色程度呈递增趋势,与HPV16／18型感染关系密切,可能对宫颈癌的发生、发展具有协同作用,可作为宫颈上皮鳞化伴增生与CINⅠ、CINⅡ、CINⅢ级及子宫颈鳞状细胞癌的诊断,作为宫颈肿瘤性及非肿瘤性的标记物。同时P16INK4A参与肿瘤的发生、发展,也初步显示利用这一基因异常靶点进行临床治疗的希望。     

高危型人乳头瘤病毒感染的子宫颈鳞状上皮组织中p16INK4α蛋白表达及其意义

目的：研究高危型人乳头瘤病毒（HPV）感染的子宫颈鳞状上皮组织中p16INK4α蛋白表达情况,探讨其在子宫颈鳞状上皮癌变过程中的作用。方法应用HC2法检测子宫颈高危型HPV-DNA,收集HPV阳性的慢性子宫颈炎组织31例、子宫颈上皮内瘤变（CIN）组织48例（CINⅠ级16例、CINⅡ级14例、CINⅢ级18例）及鳞状细胞癌组织48例,采用免疫组织化学法检测各组p16INK4α蛋白表达情况。结果慢性子宫颈炎组、CINⅠ级组、CINⅡ级组、CINⅢ级组及鳞状细胞癌组中p16INK4α蛋白阳性率分别为0（0／31）、25%（4／16）、100%（14／14）、100%（18／18）及100%（48／48）。 CINⅡ级及以上病变组中p16INK4α蛋白阳性率明显高于慢性子宫颈炎组及CINⅠ级组（P＜0.05）。结论 p16INK4α蛋白阳性表达可反映鳞状上皮异型增生,对高危型HPV感染的子宫颈鳞状上皮内病变的准确诊断具有重要参考价值。     

宫颈锥切术后HPV检测的临床意义

目的:探讨人乳头瘤病毒(HPV)在宫颈上皮内瘤样病变(CIN)行LEEP、冷刀锥切(CKC)术后的随访价值。方法:回顾分析180例行LEEP锥切、119例行冷刀锥切的CIN患者术前、术后HPV感染情况,观察锥切术后CIN的消失情况。结果:二者手术前后HPV感染率分别为:LEEP组78.3%和7.8%,CKC组64.7%和6.7%,无统计学差异,术后HPV感染率明显降低,术后HPV持续感染者宫颈病变进展率高于HPV转阴者,二者有统计学差异。结论:HPV检测在LE EP、CKC术后可作为随访有效手段。     

宫颈锥切术后HPV检测的临床意义

目的：探讨人乳头瘤病毒（HPV）在宫颈上皮内瘤样病变（CIN）行LEEP、冷刀锥切（CKC）术后的随访价值。方法：回顾分析180例行LEEP锥切、119例行冷刀锥切的CIN患者术前、术后HPV感染情况,观察锥切术后CIN的消失情况。结果：二者手术前后HPV感染率分别为：LEEP组78.3%和7.8%,CKC组64.7%和6.7%,无统计学差异,术后HPV感染率明显降低,术后HPV持续感染者宫颈病变进展率高于HPV转阴者,二者有统计学差异。结论：HPV检测在LE EP、CKC术后可作为随访有效手段。     

宫颈上皮内瘤变锥切术切缘阳性的相关因素分析

目的 宫颈上皮内瘤变(cervical intraepithelial neoplasia,CIN)是与宫颈浸润癌密切相关的一组癌前期病变.宫颈锥切术已成为CIN患者首选的治疗方法,手术病理切缘阳性是宫颈锥切术后病变复发的危险因素.本研究通过对接受宫颈冷刀锥切术(cold knifecone,CKC)或环形电切除术(loop electrosurgical excision procedure,LEEP)的CIN患者进行回顾性分析,探讨造成宫颈锥切术切缘阳性的原因,旨在降低切缘阳性率.方法 回顾性分析沈阳市妇婴医院2013-01-01-2014-12-31经阴道镜宫颈活检诊断为CIN并接受宫颈锥切术471例患者,对患者年龄、是否绝经、HPV感染、病变范围、手术方式、病变级别和术后病理提示宫颈上皮腺体受累等7种因素与宫颈锥切术后切缘阳性率做相关性分析.结果 471例宫颈锥切术患者中63例术后病理提示切缘阳性,阳性率为13.38％.单因素分析结果显示,宫颈锥切术后切缘阳性与HPV感染(x2=8.470,P＜0.05)、手术方式(x2=8.851,P＜0.01)、病变级别(x2=9.842,P＜0.05)及宫颈上皮腺体受累(x2=3.560,P＜0.05)有关,与患者年龄(t=1.293,P＞0.05)、是否绝经(x2=0.204,P＞0.05)及病变范围(x2 =0.498,P＞0.05)无关.多因素Logistic回归分析显示,HPV感染、LEEP和宫颈高级别病变是CIN锥切术后切缘阳性的危险因素.其中HPV感染因素,与HPV阴性组比较,HPV低危和高危组OR值分别为2.611(95％CI为1.214～5.615)和2.338(95％CI为1.100～4.968);病变级别因素,与CINⅠ比较,CINⅡ、CINⅢ和早期宫颈癌组OR值分别为7.903(95％CI为1.046～29.725)、27.852(95％CI为4.131～86.835)和21.548(95％CI为1.373～124.877).结论 HPV感染、LEEP及CIN高级别病变是造成宫颈锥切术切缘阳性的高危因素,在CIN制定宫颈锥切手术方式时应予以重视.     

宫颈鳞状上皮病变组织中乳头状瘤病毒和Ki-67及p16INK4a蛋白表达意义的研究

目的:探讨Ki-67、p16INK4a和人乳头状瘤病毒(HPV)在不同程度宫颈鳞状上皮病变组织中的表达及临床病理意义.方法: 采用原位分子杂交及免疫组化方法,检测HPV的不同亚型、Ki-67、p16INK4a蛋白在182例不同程度宫颈病变组织中的表达.结果: HPV在不同程度病变中总检出率52.19%(95/182);在宫颈高级别上皮内瘤变及鳞癌组中检出最多的感染类型为HPV16/18,而HPV6/11在尖锐湿疣组检出率87.50%(21/24)最高;随着宫颈病变严重程度的增加,级别升高,Ki-67、p16INK4a阳性程度呈递增趋势.Ki-67、p16INK4a与HPV16/18型感染关系密切,χ2=11.779 8, P<0.01;Ki-67也与HPV6/11型有关.结论: HPV16/18型及Ki-67、p16INK4a 在宫颈高级别上皮内瘤变及鳞癌中表达明显升高,可能对宫颈鳞癌的发生、发展具有协同作用.     

Clinical Significance of Atypical Squamous Cells of Undetermined Significance among Patients Undergoing Cervical Conization

Background: Atypical squamous cells of undetermined significance (ASCUS) feature a wide variety of cervical cells, including benign and malignant examples. The management of ASCUS is complicated. Guidelines for office gynecology in Japan recommend performing a high-risk human papillomavirus (HPV) test as a rule. The guidelines also recommend repeat cervical cytology after 6 and 12 months, or immediate colposcopy. The purpose of this study was to determine the clinical significance of ASCUS. Materials and Methods: Between January 2012 and December 2014, a total of 162 patients underwent cervical conization for cervical intraepithelial neoplasia grade 3 (CIN3), carcinoma in situ, squamous cell carcinoma, microinvasive squamous cell carcinoma, and adenocarcinoma in situ at our hospital. The results of cervical cytology prior to conization, the pathology after conization, and high-risk HPV testing were obtained from clinical records and analyzed retrospectively. Results: Based on cervical cytology, 31 (19.1%) of 162 patients were primarily diagnosed with ASCUS. Among these, 25 (80.6%) were positive for high-risk HPV, and the test results of the remaining 6 patients (19.4%) were uncertain. In the final pathological diagnosis after conization, 27 (87.1%) and 4 patients (12.9%) were diagnosed with CIN3 and carcinoma in situ, respectively. Conclusions: Although ASCUS is known as a low-risk abnormal cervical cytology, approximately 20% of patients who underwent cervical conization had ASCUS. The relationship between the cervical cytology of ASCUS and the final pathological results for CIN3 or invasive carcinoma should be investigated statistically. In cases of ASCUS, we recommend HPV tests or colposcopic examination rather than cytological follow-up, because of the risk of missing CIN3 or more advanced disease.     

Comparison of p16INK4a Immunocytochemistry with the HPV Polymerase Chain Reaction in Predicting High Grade Cervical Squamous Intraepithelial Lesions

Aim: To compare p16INK4a immunocytochemistry with the HPV polymerase chain reaction in predictinghigh grade cervical squamous intraepithelial lesions. Materials and Methods: This diagnostic case-control studywas conducted from January 2010 until December 2010. We obtained 30 samples, classified according to thedegree of cervical intraepithelial neoplasia (CIN): 11 samples for CIN 1, 9 samples for CIN 2, and 10 samples forCIN 3. HPV PCR, p16INK4a immunocytochemistry, and histopathological examination were performed on allsamples. Statistical analysis was conducted using SPSS 20.0. Results: In predicting CIN 2-3, we found p16INK4ato have similar specificity and positive predictive value as HPV PCR (95%, 97.2% vs 96.7%), but better sensitivity(87.5% vs 72.5%) and negative predictive value (82.1% vs 67.6%). The most prevalent types of high-risk HPVin our study were HPV 33, 35, 58, 52, and 16. Conclusions: p16INK4a has better diagnostic values than HPVPCR and may be incorporated in the triage of ASCUS and LSIL to replace HPV PCR. Genotype distribution ofHPV differs in each region, providing a challenge to develop HPV vaccines based on the epidemiology of HPVin that particular region.     

宫颈冷刀锥切术诊治宫颈上皮内瘤变的价值

[目的]探讨宫颈冷刀锥切术对宫颈上皮内瘤变(CIN)的诊断及治疗作用.[方法]对比126例行宫颈冷刀锥切术和阴道镜下多点活检的CIN患者的病理检查结果,分析CIN患者行宫颈冷刀锥切术的临床疗效和并发症.[结果]阴道镜下多点活检和宫颈冷刀锥切术后病理完全符合83例(占65.9％).14例(11.1％)患者锥切边缘受累;发现早期浸润癌5例,其中2例早期浸润癌仅行宫颈锥切,随访无复发.宫颈冷刀锥切术的主要并发症为出血和宫颈管狭窄,发生率分别为6.3％ (8/126)和3.9％ (5/126).[结论]宫颈锥切术比阴道镜下多点活检对宫颈上皮内瘤变的诊断更准确,并具有重要治疗作用.     

不同HPV感染状态宫颈癌细胞中INK4a表达研究

[目的]探讨不同HPV感染状态的宫颈癌细胞中INK4a基因的表达情况。[方法]提取细胞总RNA,应用逆转录—聚合酶链反应（RT-PCR）技术检测宫颈癌细胞CaSki（HPV16感染）、HeLa（HPV18感染）、C-33A（无HPV感染）中INK4a表达水平。[结果]不同HPV感染状态的宫颈癌细胞CaSki（0.3967±0.0491）,HeLa（0.5567±0.1037）,C-33A（0.5633±0.0722）中INK4amRNA表达无明显差异（P〉0.05）。[结论]不同HPV感染状态的宫颈癌细胞中INK4a表达规律趋于一致。检测INK4a基因表达对于宫颈癌的早期诊断和筛查具有重要意义。     

Expression of the p16INK4a and Ki-67 in relation to the grade of cervical intraepithelial neoplasia and high-risk human papillomavirus infection

Objective

The purposes of this study were to evaluate the expression of p16^INK4a (referred as to p16) and Ki-67 in cervical intraepithelial neoplasia (CIN), and the correlation between high-risk human papillomavirus (HPV) infection and the above biomarkers.

Methods

We analyzed 31 patients who were diagnosed with CIN at Kwandong University Myongji Hospital from October 2006 to September 2007. CIN specimens (CIN1, 12; CIN2, 6; CIN3, 13) were obtained by colposcopy-directed biopsy (CDB) or loop electrical excision procedure (LEEP). The expressions of p16 and Ki-67 were evaluated by immunohistochemical methods with antibodies to p16 and Ki67. The immunohistochemical staining results were classified into four grades: 0, 1, 2 and 3. HPV genotyping or Hybrid Capture-II test was used to detect high-risk HPV.

Results

The expression of p16 (p<0.001) and Ki-67 (p=0.003) were positively associated with CIN grade. p16 expressions increased significantly with high-risk HPV infection (p=0.014), especially HPV type 16 and 58. Ki-67 expression was not related with high-risk HPV. There was positive correlation between the expression of the p16 and Ki-67 (p=0.007).

Conclusion

CIN grade were positively related to the expression of p16 and Ki-67. p16 expressions of high-risk HPV specimens significantly increased more than Ki-67. Therefore, in the diagnosis of CIN and high-risk HPV infection, p16 can be a useful biomarker.     

Risk of cervical intraepithelial neoplasia grade 2 or worse after conization in relation to HPV vaccination status

Human papillomavirus (HPV) is essential for developing cervical cancer and precancerous lesions. Currently, three vaccines are available, which are effective as prophylaxis against HPV infection, however, limited knowledge exists about the possible effect of vaccinating women treated with conization to prevent recurrence. The aim of our study was to examine the risk of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) after conization according to HPV vaccination status. Using Danish nationwide registries, we identified women diagnosed with CIN3 on the cone (2006–2012) and their HPV vaccination status. Vaccinees were defined as women vaccinated between 3 months before until 1 year after conization. The women were followed from 1 year after conization until diagnosis of CIN2+, conization, death, emigration or end of follow-up. Cox proportional hazard regression was used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) of CIN2+ comparing vaccinees with nonvaccinees. The HR was adjusted for age, histology on cone, education, year of conization, repeat conizations and CIN2+ lesions between conization and start of follow-up. Altogether 17,128 women were included (2,074 vaccinees). There was a statistically nonsignificant lower risk of CIN2+ among vaccinees (HR_adjusted = 0.86, 95% CI: 0.67–1.09). Women vaccinated 0–3 months before tended to have a slightly lower HR of CIN2+ (HR_adjusted = 0.77, 95% CI: 0.45–1.32) than women vaccinated 0–12 months after conization (HR_adjusted = 0.88, 95% CI: 0.67–1.14), although not statistically significantly different. Our results add to the current knowledge about the potential clinical effect of vaccination as an adjunct to conization of high-grade cervical neoplasia to decrease risk of recurrence.     

高危型HPV分型和p16蛋白表达在宫颈病变诊断中的临床意义

目的:了解HPV高危型阳性的高级别鳞状上皮内瘤变(high-grade squamous intraepithelial lesion，HSIL)（CIN II-III）、慢性炎症及宫颈癌中HPV感染分型的不同分型和p16在不同组织中的表达情况，并分析其与HPV的相关性。方法:收集海南省人民医院就诊的海南籍宫颈疾病患者，其中包括HPV高危型阳性的HSIL患者100例、HPV高危型阳性慢性宫颈炎和宫颈癌患者各25例和HPV阴性慢性宫颈炎25例，收集宫颈病理组织，进行HPV分型和p16蛋白表达检测。结果:HPV高危型阳性宫颈病变中，检测出全部13种高危型亚型，主要为HPV16（16.67%）、HPV52（15.33%）、HPV58（12.67%）、HPV31（12.0%），不同宫颈病变HPV分型结果具有高度统一性，差异不具有统计学意义（P=0.999）；HPV阴性慢性宫颈炎症组织、HPV高危型阳性慢性宫颈炎症组织、HSIL组织、宫颈癌组织中p16蛋白表达阳性率分别为12.0%、72.0%、84.0%、100.0%，不同宫颈病变p16蛋白表达差异具有统计学意义（P＜0.001），随着宫颈病变的进展，p16蛋白表达逐渐增加，p16蛋白表达与宫颈病变的恶性程度具有正相关性。结论:海南籍宫颈病变患者其高危型HPV感染分型分布与目前研究一致，随着宫颈疾病进展加重， p16蛋白表达增加，HPV分型和p16蛋白联合检测对于诊断不同宫颈疾病具有重要价值。     

Combined p16INK4a and human papillomavirus testing improves the prediction of cervical intraepithelial neoplasia (CIN II-III) in Thai patients with low-grade cytological abnormalities

Thailand is in the process of developing a national cervical screening program. This study examined p16INK4a staining and HPV prevalence in abnormal cervical samples with atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesion (LSIL), to evaluate the efficacy of combined HPV and p16INK4a detection to predict CIN II-III. Totals of 125 ASCUS and 87 LSIL cases were re-evaluated by Pap test and cervical cells of ASCUS and LSIL cases were prepared on slides for p16INK4a detection by immunocytochemistry. HPV genotyping of DNA extracts was performed by GP5+/6+ PCR and reverse line blot hybridization. Histopathologic tests were performed to identify cervical lesion. Total of 212 cases were diagnosed to normal (20), ASCUS (112), LSIL (78) and HSIL (2). HPV was detected in ASCUS (49/112, 43.8%), LSIL (60/78, 76.9%) and HSIL (2/2, 100%) cases. The majority of HPV positive samples typed for high-risk HPV. 55.7% (107/192) of abnormal cases (ASCUS, LSIL and HSIL) were positive p16INK4a. For the 111 HPV DNA positive cases, 34 of 49 (69.4%) ASCUS cases and 49 of 60 (81.7%) LSIL cases were p16INK4a positive. 140 biopsies were taken and histological classified: CIN negative (65 cases), CIN I (56 cases) and CIN II-III (19 cases). HPV DNA detection predicted CIN II-III with sensitivity and specificity of 84% and 49%, whereas p16INK4a staining showed higher sensitivity (89.5%) and specificity (56.2%). The prediction of CIN II-III was significantly better by combination of positive HPV DNA and p16INK4a with 93.8% sensitivity and 59.2% specificity. Detection of HPV DNA combined with p16INK4a in cervical cells can predict CIN II-III and may improve the screening diagnosis of Thai women at risk for CIN II-III or cancer.