High-risk Human Papillomavirus DNA Testing Research Articles

A Model Approach for Assessing the Benefits of HPV Testing against Cytology in Screening for Cervical Cancer Precursors in Thailand

Objective:The aim of this study was to compare the efficacy of HPV 16/18 genotyping test, high risk HPV DNA testing, alone and in conjunction with the liquid-based cytology method in screening for cervical cancer precursors.Methods:A Markov model was used to describe the course of the cases of CIN2+ that had been detected over a 35 year period. Screening programs started at age 30 and were performed at an interval of once every five years. The model compared three strategies of HPV 16/18 genotyping with reflex cytology triage, high-risk HPV testing alone with referral to colposcopy and cytology-based screening with referral to colposcopy. We assumed the rate of patients lost to follow-up for those referred to colposcopy would be 0%. The clinical parameters were estimated using the data from a study conducted by the Thailand National Cancer Institute.Result:Of the three screening strategies evaluated, the high risk HPV DNA testing alone was the most effective for detecting CIN2+ over the 35 year study period. It detected 143 and 510 cases per 100,000 women more than the HPV 16/18 genotyping test and cytology-based strategy, respectively. The HPV genotyping test detected 368 cases per 100,000 women more than the cytology-based approach. In addition, when viewed with five year intervals, there were missed cases totaling approximately half of the detected cases screened by the cytology strategy and 10% of cases detected with screening by the HPV genotyping test.Conclusion:This study strongly indicates that HPV/DNA testing is preferable to cytology-based screening for cervical cancer precursors. However, the balance between the benefits, burdens and cost of each screening program should be considered.

Characteristics and Distribution of Penile Lesions in Croatian Men with Laboratory-Confirmed Low-Risk and High-Risk Human Papillomavirus (HPV) Infection.

Studies that compare penoscopic evaluation with the results of molecular human papillomavirus (HPV) testing are scarce. This study assessed and compared both type and distribution of various penile lesions using penoscopy (peniscopy) technique in Croatian men with different, laboratory-confirmed HPV status. From a large cohort of men attending an outpatient STD clinic for HPV testing, a total of 120 patients were randomly selected and grouped into those positive for low-risk HPV, high-risk HPV, both low-risk and highrisk HPV, and those with negative results. Samples for HPV-DNA detection were taken by penile brushing and tested with the hc2 HPV DNA Test using Hybrid Capture 2 technology. Lesions were observed by photocolposcope after the application of aqueous 5% acetic acid, and classified as flat (macular), papular, papillary, classical condyloma, PIN-suspicious and non-specific lesions. The results have shown that flat and non-specific acetowhite lesions were the most common overall. All groups differed significantly with respect to papular and papillary lesions. A combination of heterogeneous lesions (i.e., a mixed penoscopic pattern) was commonly observed in all HPV-positive groups, but was significantly lower in the HPV-negative group. A majority of lesions were located in the coronal sulcus, and the four groups differed with respect to the location only considering the lesions of the penile shaft. Distribution of lesions in different sites did not appear to be significantly different with respect to the group, although differences within the high-risk HPV group and the group with both low-risk and high-risk HPV were detected. Penoscopy is relevant, but not a conclusive diagnostic tool for differentiating HPV from non-HPV findings in men - thus combining it with an HPV DNA test represents a more reliable approach.

Prevalence of High-Risk Human Papillomavirus (HPV) among Negative Visual Inspection of Acetic Acid (VIA)

Objective: Persistence of high-risk HPV infection is known to be the
 major cause of cervical cancer. It is important to differentiate the
 genotype of HPV infection, whether it is high, intermediate or low
 risk. The aim of this study was to assess the prevalence of high-risk
 HPV types among Indonesian women with negative VIA.
 Method: We analyzed cervical swabs from 1,214 patients with negative
 VIA. By using INNO-Lipa HPV DNA test, we detected the HPV
 DNA and its genotype.
 Result: From the 1,214 women with negative VIA, 48 (3.95%) samples
 were confirmed to have positive HPV DNA by using PCR and
 electrophoresis. However, hybridization test were not able to detect
 HPV genotypes in 9 samples. These 9 samples were tested again
 with PCR and electrophoresis and resulted in negative HPV DNA.
 Among the remaining 39 samples (3.21%), we detected 19 types of
 HPV, consisting of 13 types of high-risk HPV, 5 types of low-risk HPV,
 and 1 type of unknown HPV (type X).
 Conclusion: Among patients with negative VIA, 3.21% was found to
 be positive for HPV DNA. From this percentage, the prevalence of
 high-risk HPV is higher than the low-risk and unknown HPV. Therefore
 we cannot ignore results of negative VIA, particularly in highrisk
 group, because there is a slight possibility that presence of HPV
 can be identified, especially the high risk ones which have a tendency
 to be persistent. We support the importance of HPV DNA test
 as cervical cancer screening method.
 [Indones J Obstet Gynecol 2014; 3: 153-156]
 Keywords: cervical cancer, high-risk HPV, negative VIA

Aptima HPV Assay versus Hybrid Capture® 2 HPV test for primary cervical cancer screening in the HPV FOCAL trial

BackgroundCervical cancer screening programs are switching from Pap screening to high-risk HPV testing. ObjectivesTo compare the Aptima HPV Assay (AHPV) with the Hybrid Capture® 2 High-Risk HPV DNA Test® (HC2) for primary cervical screening. Study designHPV FOCAL is a randomized trial comparing HC2 to liquid-based cytology (LBC) for screening women aged 25–65. AHPV and HC2 were compared at the baseline screen (n=3473). Genotyping was by the Aptima HPV 16 18/45 Genotype Assay. We assessed HPV genotyping and reflex LBC for colposcopy triage. ResultsAHPV/HC2 agreement was 96.5% (kappa 0.76); positive agreement was 77.4%. The AHPV positive rate was 7.2% vs. 8.4% for HC2 (p=0.06). Based on HC2 screening, round 1 CIN2 and CIN3+ rates were 9.2/1000 and 5.2/1000 respectively. Using HC2 as the comparator test, AHPV CIN2+ and CIN3+ relative sensitivities were 0.96 and 1.00 (p=1.00) respectively. High-grade reflex LBC and HPV 16 infection were significantly associated with CIN3+. AHPV specificity was 0.94 vs. 0.93 (p=0.05) for HC2. Compared with triage of HC2+ with abnormal cytology or HPV persistence for 12 months, colposcopy referral would be significantly reduced (38.3/1000 vs. 60.8/1000; p<0.001) if AHPV+ women with abnormal LBC and HPV 16/18/45 were referred at baseline. CIN2+ and CIN3+ detection rates were not significantly different for the two strategies. ConclusionsAHPV vs. HC2 screening had equivalent CIN2+ and CIN3+ detection. Triage of AHPV+ by abnormal reflex LBC and the presence of HPV 16/18/45 would result in a significantly lower colposcopy referral rate with similar CIN2+ and CIN3+ detection rates as the overall HC2+ referral algorithm.

A comparison of different human papillomavirus tests in PreservCyt versus SurePath in a referral population—PREDICTORS 4

BackgroundTwo transport media, PreservCyt and SurePath, are widely used for cervical cytology screening. There are concerns that they may perform differently for HPV testing. ObjectivesA comparison of the performance of six different HPV tests in SurePath and PreservCyt in a referral population using two samples from each woman. The primary goal was to compare the performance of each test in the two media. Comparisons between assays and viral load comparisons between media were secondary aims. Study designTwo cervical samples were collected in random order at the same visit in women with abnormal cytology. One sample was placed in 20ml of PreservCyt and the other in 10ml of SurePath. Aliquots were taken for 4 DNA based tests: digene HC2 High-Risk HPV DNA Test, Abbott Realtime, BD Onclarity and Genera PapType, an RNA based test—: Hologic Aptima and a protein test: OncoHealth. Results630 sample pairs were included in the analyses. For all tests except the protein test sensitivities were in excess of 90% for CIN2+ and 95% for CIN3+ for both media and with no significant differences except for a lower sensitivity for CIN2+ of Aptima in SurePath (93% vs 98%, P=0.005). Specificity for <CIN2 was significantly better in Surepath for HC2, RealTime and Aptima, and generally lower relative signal strengths were seen with SurePath except for Onclarity, especially when it was the second sample. ConclusionsWe found similar sensitivity for CIN3+ in PreservCyt and SurePath for 5 nucleic acid tests in the two media in a referral population, but signal strength and positivity rates were lower in SurePath except for the Onclarity test. These results need to be replicated in a screening population.

Human papillomavirus mRNA and DNA testing in women with atypical squamous cells of undetermined significance: A prospective cohort study.

In this prospective cohort study, we compared the performance of human papillomavirus (HPV) mRNA and DNA testing of women with atypical squamous cells of undetermined significance (ASC-US) during cervical cancer screening. Using a nationwide Danish pathology register, we identified women aged 30-65 years with ASC-US during 2005-2011 who were tested for HPV16/18/31/33/45 mRNA using PreTect HPV-Proofer (n = 3,226) or for high-risk HPV (hrHPV) DNA using Hybrid Capture 2 (HC2) (n = 9,405) or Linear Array HPV-Genotyping test (LA) (n = 1,533). Women with ≥1 subsequent examination in the register (n = 13,729) were followed for up to 9.5 years for high-grade cervical intraepithelial neoplasia (CIN) or cancer. After 3 years' follow-up, mRNA testing had higher specificity for CIN3 or worse (CIN3+) than HC2 testing (88.1% [95% confidence interval (CI): 86.8-89.6%] versus 59.3% [95% CI: 58.1-60.4%]) and higher positive predictive value (PPV) (38.2% [95% CI: 33.8%-43.1%] versus 19.5% [95% CI: 17.8-20.9%]). However, the sensitivity of mRNA testing was lower than that of HC2 testing (66.7% [95% CI: 59.3-74.5%] versus 97.0% [95% CI: 95.5-98.4%]), and women testing mRNA negative had higher 3-year risk for CIN3+ than those testing HC2 negative (3.2% [95% CI: 2.2-4.2%] versus 0.5% [95% CI: 0.3-0.7%]). Patterns were similar after 18 months and 5 years'; follow-up; for CIN2+ and cancer as outcomes; across all age groups; and when comparing mRNA testing to hrHPV DNA testing using LA. In conclusion, the HPV16/18/31/33/45 mRNA test is not optimal for ASC-US triage due to its low sensitivity and the substantial risk for precancer following a negative test.

Correlates of women's intentions to be screened for human papillomavirus for cervical cancer screening with an extended interval.

BackgroundHigh-risk HPV DNA testing has been proposed as a primary tool for cervical cancer screening (HPV-CCS) as an alternative to the Papanicolaou cytology- method. This study describes factors associated with women’s intentions to attend cervical cancer screening if high-risk HPV DNA testing (HPV-CCS) was implemented as a primary screening tool, and if screening were conducted every 4 years starting after age 25.MethodsThis online survey was designed using the Theory of Planned Behaviour to assess factors that impact women’s intentions to attend HPV-CCS among women aged 25–69 upon exit of the HPV FOCAL trial. Univariate and regression analyses were performed to compare the demographic, sexual history, and smoking characteristics between women willing and unwilling to screen, and scales for intention to attend HPV-CCS. A qualitative analysis was performed by compiling and coding the comments section of the survey.ResultsOf the 981 women who completed the survey in full, only 51.4 % responded that they intended to attend HPV-CCS with a delayed start age and extended screening interval. Women who intended to screen were more likely to have higher education (AOR 0.59, 95 % CI [0.37, 0.93]), while both positive attitudes (AOR 1.26, 95 % CI [1.23, 1.30]) and perceived behavior control (AOR 1.06, 95 % CI [1.02, 1.10]) were significant predictors of intention to screen. Among women who provided comments in the survey, a large number of women expressed fears about not being checked more than every 4 years, but 12 % stated that these fears may be alleviated by having more information.ConclusionsAcceptability of increased screening intervals and starting age could be improved through enhanced education of benefits. Program planners should consider measures to assess and improve women’s knowledge, attitudes and beliefs prior to the implementation of new screening programs to avoid unintended consequences.

Clinical investigation of taking Cervista high-risk human Papilloma virus DNA test and cytological test in the same sample

Objective To explore the feasibility of taking Cervista high-risk human Papilloma virus DNA (Cervista HR HPVDNA) test and Thinprep cytologic test in the same sample, and to assess the availability and significance of Cervista HR HPVDNA in detecting HPV infection in people, also to study the correlation of Cervista A9 group with high grade cervical dysplasia and the value of HPV16/18 in diagnosing cervical dysplasia. Methods Totally 148 cases diagnosed in gynecology clinic during March to April, aging 20 to 65, cytological test ≥ASCUS (atypical squamous cells undetermined significance) were involved in the investigation group, and 153 cases with normal cytological test at the same time were involved in the control group. Cytological test and Cervista high-risk human Papilloma virus DNA test were implemented at the same time on two groups, cases with one of the test method tested abnormal were further biopsied under the colposcope if necessary. Results Cervista HR HPVDNA infection rate was 83.78% in the investigation group and 18.30% in the control group with statistic difference (P 0.05). We further founded that A9 group take the large proportion of Cervista HR HPVDNA infection, and co-infection by 2 or 3 genotypes tested in part grades and A9 group related with Pathology≥CINⅡ(P<0.05). The sensitivity, specificity, positive-predictive value and negative-predictive value of Cervista HR HPVDNA for detecting all cases of CINⅡ were 90.9%, 18.1%, 22.7%, and 88.2%, respectively. A portion (30.6%) of the Cervista HR HPVDNA positive cases showed HPV16/18 positive, while none showed in the Cervista HR HPVDNA negative cases. HPV16/18 infection rate in normal, CINⅠ, CINⅡ, CINⅢ, and Cervical carcinoma were 13.33%, 37.50%, 50.00%, 75%, and 100% with significant difference(Fisher exact Test P<0.05). Conclusions Cervista HR HPVDNA test was feasible as an Cervical carcinoma screening method. The method of combining Cervista HR HPVDNA test with cytological test in the same sample deserves promotion as its easy operating and definite effect. Key words: Biopsy; Uterine cervical neoplasms/DI; Papillomaviridae/ME

Associations between sexually transmitted infections, high-risk human papillomavirus infection, and abnormal cervical Pap smear results in OB/GYN outpatients.

ObjectiveThis study aimed to examine the meaning and usefulness of sexually transmitted infection (STI) test when caring for patients who have abnormal cervical cytology and/or positive high-risk human papillomavirus (HPV) DNA test results.MethodsAmong patients who underwent liquid-based cervical cytology and HPV DNA tests at the Obstetrics and Gynecology outpatient clinic, 800 patients who showed abnormal cervical cytology were compared with 200 patients in the control group. Both groups were simultaneously tested via multiplex real-time polymerase chain reaction for seven types of STI-causative microorganisms.ResultsThe positive rate of high-risk HPV infection in total STIs positive group was 1.47 times higher than that of total STIs negative group. The probability of a cytological diagnosis of a grade equal to or higher than atypical squamous cells-cannot exclude high grade squamous intraepithelial lesion (ASC-H) was significantly higher in patients testing positive for total STIs (1.46 times), Chlamydia trachomatis (3.21 times), or Mycoplasma genitalicum (3.58 times) than in those testing negative. The total STIs positive rate was significantly higher for those having a cytological diagnosis of a grade equal to or higher than atypical squamous cells of undetermined significance (ASC-US) when high-risk HPV test result was negative.ConclusionCorrelations were present not only between STIs and high-risk HPV infection but also between abnormal cervical cytology and STIs. Therefore, additional evaluation of STIs will be helpful to appropriately diagnose and treat patients with abnormal cervical cytology, positive results on high-risk HPV DNA test, or a cytological diagnosis of ASC-US despite negative high-risk HPV DNA test result.

Clinical validation of high risk HPV DNA testing versus cytology for predicting cervical cancer

Clinical validation of high risk HPV DNA testing versus cytology for predicting cervical cancer

Comparison of Human Papillomavirus Detection in Urine and Cervical Samples Using High-Risk HPV DNA Testing in Northern Thailand.

Objective. To evaluate the performance of high-risk human papillomavirus (HPV) DNA testing in urine samples compared to that of cervical sample testing in Northern Thailand. Methods. Paired urine and cervical samples were collected during the follow-up of women with a previous positive HPV test. HPV testing was performed using the Cobas 4800 HPV Test. Linear Array assay was used for genotyping in selected cases. Results. Paired urine and cervical samples were obtained from 168 women. Of 123 paired samples with valid results, agreement in the detection of high-risk HPV DNA was present in 106 cases (86.2%), with a kappa statistic of 0.65 (substantial agreement). Using the cervical HPV results as a reference, the sensitivity of urine HPV testing was 68.6% (24/35) and the specificity 93.2% (82/88). For the detection of histologic high-grade squamous intraepithelial lesion or worse (HSIL+), the sensitivity of urine HPV testing was 80.0% (4/5) and the specificity 78.0% (92/118). Conclusion. Although urine HPV testing had a rather low sensitivity for HPV detection, its sensitivity for histologic HSIL+ detection was high. For clinical use of urine HPV testing, standardization of specimen collection and processing techniques or application of a more sensitive test, especially in the detection of HPV52 and HPV58, is necessary.

Triage of ASC-H: A meta-analysis of the accuracy of high-risk HPV testing and other markers to detect cervical precancer.

Women with a cytological diagnosis of atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H) are usually immediately referred for colposcopy. However, triage may reduce the burden of the diagnostic workup and prevent overtreatment. A meta-analysis was conducted to assess the accuracy of high-risk human papillomavirus (hrHPV) testing and testing for other molecular markers for the detection of grade 2 cervical intraepithelial neoplasia or worse (CIN2+) or grade 3 cervical intraepithelial neoplasia or worse (CIN3+) in women with ASC-H. An additional question that was assessed was whether triage would be useful in light of the relatively high pretriage probability of underlying precancer. The pooled absolute sensitivity and specificity of the Hybrid Capture 2 (HC2) assay for CIN2 + (derived from 19 studies) were 93% (95% confidence interval [CI], 89%-95%) and 45% (95% CI, 41%-50%), respectively. p16(INK4a) staining (only 3 studies) had similar sensitivity (93%; 95% CI, 75%-100%) but superior specificity (specificity ratio, 1.69) to HC2 for CIN2+. Testing for paired box 1 gene methylation (only 1 study) showed a superior specificity of 95% (specificity ratio, 2.08). The average pretest risk was 34% for CIN2 + and 20% for CIN3+. A negative HC2 result decreased this to 8% and 5%, respectively, whereas a positive result upgraded the risk to 47% and 28%, respectively. Because of the high probability of precancer with a diagnosis of ASC-H, the utility of triage is limited. The usual recommendation for referring women with ASC-H for colposcopy is not altered by a positive triage test, whatever test is used. A negative hrHPV DNA or p16(INK4a) test may allow repeat testing, but this recommendation will depend on local decision thresholds for referral.

Three-year longitudinal data on the clinical performance of the Abbott RealTime High Risk HPV test in a cervical cancer screening setting

BackgroundTesting cervical smears for the presence of high-risk human papillomaviruses (hrHPV) increases the sensitivity for detecting women with underlying high-grade cervical intraepithelial neoplasia (CIN) and provides better and longer protection against invasive cervical cancer compared to cytology testing alone. The Abbott RealTime High Risk HPV test (RealTime) is a hrHPV DNA test with concurrent partial genotyping for HPV16 and HPV18 and aggregate detection of 12 other hrHPV types that have been extensively analytically and clinically evaluated over the last 6 years. Objectives and study designTo provide the first 3-year longitudinal data regarding the clinical performance of RealTime, the risk of CIN2+ according to various negative baseline characteristics, and baseline and future risk for CIN2+ at 3 years for women with baseline infection with various hrHPV types were assessed in a cohort of 3,920 Slovenian women that had hrHPV DNA and/or cytology in 36- to 48-month follow-up results after a baseline screening round in 2009/2010. ResultsA total of 36 CIN2+ cases were identified in the second screening round. Of these, 17 CIN2+ cases were identified passively through questionnaires/data registries and 19 cases actively as the result of actions triggered by second-round cytology and/or HPV test results. Accumulation of CIN2+ cases during follow-up occurred predominantly in woman with normal cytology at baseline. Among women >30 years old, significantly better protection against CIN2+ at 3 years was associated with a negative hrHPV DNA result at baseline (risk for CIN2+ 0.04% [95 CI, 0.00–0.22%]) than by normal cytology at baseline (risk for CIN2+ 0.68% [95 CI, 0.40–1.08%]). Women with baseline HPV16 infection had a significantly higher risk of CIN2+ at baseline (21.9% [95 CI, 15.2–30.4%]) and baseline plus future risk at 3 years for CIN2+ (33.3% [95 CI, 24.7–44.0%]) in comparison to women with baseline non-HPV16/18 hrHPV infection (7.0% [95 CI, 4.6–10.2%]) or those that were hrHPV-positive (11.7% [95 CI, 9.1–14.9%]). Conclusions3-year longitudinal data reinforce evidence from previous studies that RealTime can be safely used in primary HPV-based cervical cancer screening. Concurrent partial genotyping for HPV16/18 should be strongly considered as a triage method for HPV screen-positive women.

Comparison of urine specimen collection times and testing fractions for the detection of high-risk human papillomavirus and high-grade cervical precancer

BackgroundUrine testing for high-risk human papillomavirus (HR-HPV) detection could provide a non-invasive, simple method for cervical cancer screening. ObjectivesWe examined whether HR-HPV detection is affected by urine collection time, portion of urine stream, or urine fraction tested, and assessed the performance of HR-HPV testing in urine for detection of cervical intraepithelial neoplasia grade II or worse (CIN2+). Study designA total of 37 female colposcopy clinic attendees, ≥30 years, provided three urine samples: “first void” urine collected at home, and “initial stream” and “mid-stream” urine samples collected at the clinic later in the day. Self- and physician-collected brush specimens were obtained at the same clinic visit. Colposcopy was performed and directed biopsies obtained if clinically indicated. For each urine sample, HR-HPV DNA testing was conducted for unfractionated, pellet, and supernatant fractions using the Trovagene test. HR-HPV mRNA testing was performed on brush specimens using the Aptima HPV assay. ResultsHR-HPV prevalence was similar in unfractionated and pellet fractions of all urine samples. For supernatant urine fractions, HR-HPV prevalence appeared lower in mid-stream urine (56.8%[40.8–72.7%]) than in initial stream urine (75.7%[61.9–89.5%]). Sensitivity of CIN2+ detection was identical for initial stream urine and physician-collected cervical specimen (89.9%[95%CI=62.7–99.6%]), and similar to self-collected vaginal specimen (79.1%[48.1–96.6%]). ConclusionThis is among the first studies to compare methodologies for collection and processing of urine for HR-HPV detection. HR-HPV prevalence was similar in first void and initial stream urine, and was highly sensitive for CIN2+ detection. Additional research in a larger and general screening population is needed.

Budget Impact Analysis Of High-Risk Hpv Dna (Hrhpv) Test With 16/18 Genotyping As A Primary Screening Method For Cervical Cancer In Greece

Budget Impact Analysis Of High-Risk Hpv Dna (Hrhpv) Test With 16/18 Genotyping As A Primary Screening Method For Cervical Cancer In Greece

The American Society for Colposcopy and Cervical Pathology Guidelines for Unsatisfactory Pap Smears with High-Risk Human Papillomavirus Co-testing: A Quality Assurance Review

The recommendation for unsatisfactory Pap smears endorsed by the new American Society for Colposcopy and Cervical Pathology (ASCCP) 2013 guidelines is based on the high-risk human papillomavirus (HPV) DNA (hr-HPV) testing status. For women with unsatisfactory cytology with either an unknown or a negative HPV test result, repeat cytology in 2 to 4 months is recommended. …

Value of PAX1 Methylation Analysis by MS-HRM in the Triage of Atypical Squamous Cells of Undetermined Significance.

Detection of cervical high grade lesions in patients with atypical squamous cells of undetermined significance (ASCUS) is still a challenge. Our study tested the efficacy of the paired boxed gene 1 (PAX1) methylation analysis by methylation-sensitive high-resolution melting (MS-HRM) in the detection of high grade lesions in ASCUS and compared performance with the hybrid capture 2 (HC2) human papillomavirus (HPV) test. A total of 463 consecutive ASCUS women from primary screening were selected. Their cervical scrapings were collected and assessed by PAX1 methylation analysis (MS-HRM) and high-risk HPV-DNA test (HC2). All patients with ASCUS were admitted to colposcopy and cervical biopsies. The Chi- square test was used to test the differences of PAX1 methylation or HPV infection between groups. The specificity, sensitivity, and accuracy for detecting CIN2 + lesions were: 95.6%, 82.4%, and 94.6%, respectively, for the PAX1 MS-HRM test; and 59.7%, 64.7%, and 60.0% for the HC2 HPV test. The PAX1 methylation analysis by MS-HRM demonstrated a better performance than the high-risk HPV-DNA test for the detection of high grade lesions (CIN2 +) in ASCUS cases. This approach could screen out the majority of low grade cases of ASCUS, and thus reduce the referral rate to colposcopy.

Exploration of treatment strategies for normal cytology smears with reactive cellular changes

ObjectiveTo evaluate the use of high-risk humanpapillomavirus (HR-HPV) DNA testing in women who have normal cytology result with reactive cellular changes to identify high risk patients of developing precancerous cervical lesions and cervical cancer. Study designOutpatient patients with normal liquid-based cytology (LCT) results showing reactive cellular changes (case group, n=1085) and normal LCT without reactive cellular changes (control group, n=1085) were recruited from cervical clinics at the International Peace Maternity & Child Health Hospital from January 2012 to December 2013. The HPV status and cervical biopsy pathology results were analyzed. ResultsThe HR-HPV positive rate of the case group (598/1085) was higher than that of the control group (163/1085) (P<0.001). HR-HPV prevalence among CIN1, CIN2, CIN3 and cervical cancer was 73%, 87%, 100%, and 100% respectively (P<0.05). In patients with positive HR-HPV results, more CIN2+ were found significantly in case group (37/598) than those in control group (3/163), P=0.027. The sensitivity of diagnosis of CIN2+ lesions by HR-HPV testing was 92.5%, the specificity was 36%, the positive predicted value was 8.6%, and the negative predictive value was 98.6%. The incidence of CIN2+ lesions was not different among different age groups (P>0.05). ConclusionReactive cellular changes in normal cervical smears should be further investigated. HR-HPV testing could be used as an effective triage in cases of reactive cellular changes. Colposcopy is recommended for those cases showing reactive cellular changes combined with HR-HPV positivity to reduce the risk of failure to diagnose cervical cancer and precancerous lesions.

P16(INK4a)/Ki-67 dual stain cytology for cervical cancer screening in Thika district, Kenya.

BackgroundThe identification of suited early detection tests is one among the multiple requirements to reduce cervical cancer incidence in developing countries.MethodsWe evaluated p16INK4a/Ki-67 dual-stain cytology in a screening population in Thika district, Kenya and compared it to high-risk human papillomavirus (HR-HPV) DNA testing and visual inspection by acetic acid (VIA) and Lugol’s iodine (VILI).ResultsValid results for all tests could be obtained in 477 women. 20.9 % (100/477) were tested positive for HR-HPV DNA, 3.1 % (15/477) had positive VIA/VILI and 8.2 % (39/477) positive p16INK4a/Ki-67 cytology. Of 22 women that showed up for colposcopy and biopsy, 6 women were diagnosed with CIN3 and two with CIN2. All women with CIN2/3 were negative in VIA/VILI screening and positive by HR-HPV DNA testing. But HPV was also positive in 91.7 % (11/12) of women with normal histology. p16INK4a/Ki-67 cytology was positive in all 6 women with CIN3, in one of the two CIN2 and in only 8.3 % (1/12) of women with normal histology.Conclusionsp16INK4a/Ki-67 cytology is an interesting test for further studies in developing countries, since our findings point to a lower fraction of false positive test results using p16INK4a/Ki-67 cytology compared to HPV DNA testing in a Kenyan screening population. VIA/VILI missed all histology-proven CIN2/3.

The Accuracy of p16/Ki-67 and HPV Test in the Detection of CIN2/3 in Women Diagnosed with ASC-US or LSIL.

The objective of this study was to compare the accuracies of double staining for p16/Ki-67 and the molecular test for high-risk HPV (hr-HPV) to identify high-grade cervical intraepithelial neoplasia (CIN2/CIN3) in women with cervical cytology of atypical squamous cells of undetermined significance (ASC-US) and low-grade squamous intraepithelial lesion (LSIL). Data were collected from 201 women who underwent cervical cytology screening in the Barretos Cancer Hospital and their results were categorized as ASC-US (n=96) or LSIL (n=105). All patients underwent colposcopy with or without cervical biopsy for diagnosis of CIN2/CIN3. The hr-HPV test (Cobas 4800 test) and immunocytochemistry were performed to detect biomarkers p16/Ki-67 (CINtec PLUS test). Two samples (1 ASC-US/1 LSIL) were excluded from the analysis due to inconclusive results of the histologic examination. There were 8 cases of CIN2/CIN3 among 95 women with ASC-US (8.4%), and 23 cases of CIN2/CIN3 among 104 women with LSIL (22.1%). In the group of women with ASC-US, the sensitivity and specificity in diagnosing CIN2/CIN3 were 87.5% and 79.5% for the HPV test and 62.5% and 93.1% for p16/Ki-67. Among women with LSIL, the sensitivity and specificity in the diagnosis of CIN2/CIN3 were 87% and 34.7% for the HPV test and 69.6% and 75.3% for immunocytochemistry. Superior performance was observed for p16/Ki-67 double staining, especially among women under 30 for whom the test had an area under the ROC curve of 0.762 (p<0.001). Both p16/Ki-67 double staining and the hr-HPV DNA test had similar performance in predicting high-grade cervical intraepithelial neoplasia among women with ASC-US. The best performance was observed in women aged >30 years. In younger women (≤30 years) with LSIL, p16/Ki-67 had greater accuracy in identifying precursor lesions. Among women >30 years diagnosed with LSIL, the two methods showed similar performance.