Prevalence and Risk Factors of Human Papillomavirus Infection in 18-Year-Old Women: Baseline Report of a Prospective Study on Human Papillomavirus Vaccine.

OBJECTIVES: Little is known about the epidemiology of human papillomavirus (HPV) in Italy before the age of 25. At the European Institute of Oncology, a prospective observational study on cervical HPV infection in 18-year-old women undergoing quadrivalent HPV vaccination is ongoing. METHODS: At the first visit before vaccination, all the young women answered an epidemiological questionnaire, and then, the presence of high-risk HPV (hrHPV) was tested. Samples positive for hrHPV were genotyped. Liquid-based cytology was done only to women declaring not to be virgins. Any positivity at cytology or HPV testing was completed with colposcopy and eventually biopsies. RESULTS: Seven hundred and thirty women were enrolled. Two hundred sixty-six women were virgins; 7 (2.6%) of these resulted positive to hrHPV: 1 had HPV16 and CP6108, whereas the other 6 resulted negative at genotyping. Of the 464 nonvirgins, 61 (13.1%) were HPV positive: 19 had HPV16, 4 were positive to HPV18 with other hrHPVs, 25 to other hrHPVs, 7 to low-risk HPV, whereas 13 resulted negative at genotyping. HPV positivity was significantly associated to both smoking and having more than 3 partners. Cervical cytology was negative in 433 cases (93.3%), ASC-US in 10 cases (2.2%), low-grade squamous intraepithelial lesion in 20 cases (4.3%), and ASC-H in 1 case (0.2%). No CIN2+ was identified. CONCLUSIONS: Overall, we found a low positivity to HPV in this population; however, the rate of HPV positivity was significantly related to smoking and sexual life. The cytology result low-grade squamous intraepithelial lesion was more frequent than in the screening population, whereas no CIN2+ was identified, confirming the indication to avoid screening at this age.

Chlamydia trachomatis infection and HPV/Chlamydia trachomatis co-infection among HPV-vaccinated young women at the beginning of their sexual activity.

PURPOSE: This study investigated the prevalence of Chlamydia trachomatis infection, co-infection with Human Papillomavirus (HPV) and associated risk factors in a cohort of sexually active young women enrolled in an ongoing trial on HPV vaccination at the European Institute of Oncology (IEO, Milan, Italy). METHODS: Cervical samples were collected from 591 girls (median age 18.8 years) at the beginning of their sexual activity. At the time of sample collection, 354 women had not yet been vaccinated, and 237 women had been vaccinated for at least 12 months. All samples were analyzed through a molecular assay for the detection of C. trachomatis infection. Demographic, behavioral risk factors and high-risk HPV (HR-HPV) status were investigated. RESULTS: The prevalence of C. trachomatis infection was 4.9 % and HPV/C. trachomatis co-infection rate was 1.5 %. The exact analysis has not underlined statistical significance for the variables considered, except for the infection with HR-HPV (p < 0.001). The prevalence of C. trachomatis infection among women who had not been immunized and those already vaccinated was similar (5.6 vs 3.8 %). However, the rate of HPV/C. trachomatis co-infection was twice as high in unvaccinated women (2 %) compared to vaccinated women (0.8 %). CONCLUSIONS: Over 16 % of young women had at least one of the two STIs investigated. The risk of C. trachomatis infection was higher in HR-HPV infected compared to HR-HPV uninfected young women. The rate of co-infection was halved in HPV-vaccinated compared to unvaccinated women. This study underlines that HPV vaccination can confer benefits also in terms of co-infections prevention, leading to a decreased risk of developing cervical malignancies.

Evaluating HPV-negative CIN2+ in the ATHENA trial.

A post hoc analysis of the ATHENA study was performed to determine whether true HPV-negative cervical lesions occur and whether they have clinical relevance. The ATHENA database was searched for all CIN2 or worse (CIN2+) cases with cobas HPV-negative results and comparison was made with Linear Array (LA) and Amplicor to detect true false-negative HPV results. Immunostaining with p16 was performed on these cases to identify false-positive histology results. H&E slides were re-reviewed by the study pathologists with knowledge of patient age, HPV test results and p16 immunostaining. Those with positive p16 immunostaining and/or a positive histopathology review underwent whole tissue section HPV PCR by the SPF10/LiPA/RHA system. Among 46,887 eligible women, 497 cases of CIN2+ were detected, 55 of which tested negative by the cobas(®) HPV Test (32 CIN2, 23 CIN3/ACIS). By LA and/or Amplicor, 32 CIN2+ (20 CIN2, 12 CIN3/ACIS) were HPV positive and categorized as false-negatives by cobas HPV; nine of 12 false-negative CIN3/ACIS cases were p16+. There were 23 cases (12 CIN2, 11 CIN3/ACIS) negative by all HPV tests; seven of 11 CIN3/ACIS cases were p16+. H&E slides were available for six cases for re-review and all were confirmed as CIN3/ACIS. Tissue PCR was performed on the six confirmed CIN3/ACIS cases (and one without confirmation): four were positive for HPV types not considered oncogenic, two were positive for oncogenic genotypes and one was indeterminate. In summary, subanalysis of a large cervical cancer screening study did not identify any true CIN3/ACIS not attributable to HPV.

HPV-Testing in Follow-up of Patients Treated for CIN2+ Lesions.

Persistent positivity of HPV-DNA testing is considered a prognostic index of recurrent disease in patients treated for CIN2+. HPV detection, and particularly genotyping, has an adequate high rate of sensitivity and specificity (along with an optimal reproducibility), for accurately predicting treatment failure, allowing for an intensified monitoring activity. Conversely, women with a negative HPV-test 6 months after therapy have a very low risk for residual/recurrent disease, which leads to a more individualized follow-up schedule, allowing for a gradual return to the normal screening scheme. HPV testing should be routinely included (with or without cytology) in post-treatment follow-up of CIN2+ patients for early detection of recurrence and cancer progression. HPV genotyping methods, as a biological indicator of persistent disease, could be more suitable for a predictive role and risk stratification (particularly in the case of HPV 16/18 persistence) than pooled HPV-based testing. However, it is necessary to be aware of the performance of the system, adhering to strict standardization of the process and quality assurance criteria.

Clinical and analytical performance of the BD Onclarity™ HPV assay for detection of CIN2+ lesions on SurePath samples.

BACKGROUND: The novel BD OnclarityTM HPV assay (Onclarity) on the BD Viper™ LT system (BD Diagnostics, Sparks, MD), detects E6/E7 DNA from 13 high-risk HPV genotypes and HPV66. We compared the analytical and clinical performance of the Onclarity Assay to that of Hybrid Capture 2 and LINEAR ARRAY using adjudicated histological outcomes from Danish women referred for colposcopy. METHODS: 276 women from Copenhagen, Denmark were referred for colposcopy with abnormal cytology and/or a positive HPV test. Two samples for HPV analysis were taken in BD SurePath™ and in the BD cervical brush diluent (CBD) media. ClinicalTrial gov. identifier: NCT01671462, Ethical Approval: H-4-2012-070. RESULTS: Histology was normal in 84 (31%) women, 70 (26%) had CIN1, 47 (17%) CIN2, and 68 (25%) had CIN3. The Onclarity assay detected 67 out of 68 (99%) ≥CIN3 and 113/115 (98%) ≥CIN2. The specificities for

hr-HPV testing in the management of women with ASC-US+ and in the follow-up of women with cytological abnormalities and negative colposcopy. Recommendations of the Italian group for cervical cancer screening (GISCi).

Compared to spontaneous screening, an organized screening programme is characterized by the presence of protocols and recommendations for all stages including follow-up. Despite the availability of well-functioning screening programmes throughout the country, the follow-up protocol after an abnormal Pap test and negative colposcopy is not clearly defined in Italy, and there is no uniformity of indications. HPV testing for oncogenic human papillomavirus (hr-HPV) has a high negative predictive value (NPV) and high positive predictive value (PPV) for CIN2+ and its employment can reduce follow-up assessments. In order to provide indications about the management of women with ASC-US+ and the follow-up of women with cytological abnormalities and negative colposcopy, a literature analysis was carried out, taking into consideration European and American guidelines and good practice recommendations from the most important scientific associations and regulatory agencies. GISCi (Italian Group for Cervical Screening) drafted recommendations for the management of women with ASC-US, L-SIL, ASC-H, AGC, and H-SIL until their return to the routine screening interval. This protocol can be applied not only in the management of abnormal Pap smears in cytology-based programmes, but also in the management of abnormal Pap test triage after HPV positive test when HPV is the primary screening test. The protocols approved within the screening programmes must have an extensive consensus among all involved professionals, including any that women might meet outside the programme.

The predictive value of human papillomavirus testing for the outcome of patients conservatively treated for stage IA squamous cell cervical carcinoma.

BACKGROUND: Although it is hypothesised that human papillomavirus (HPV) testing may have a role in surveillance of patients conservatively treated for stage IA squamous cell cervical carcinoma, research on this topic has been minimal. OBJECTIVES: To determine: (1) the changes in HPV test result from treatment onward; (2) the time to viral clearance; and (3) the negative predictive value (NPV) and positive predictive value (PPV) of HPV test result for the detection of CIN2 or worse (CIN2+) during follow-up. STUDY DESIGN: In a multicentre retrospective follow-up study of a consecutive series (1997-2009) of 91 patients, longitudinal outcome measures were estimated as cumulative probabilities using the Kaplan-Meier method. RESULTS: For patients testing HPV-positive at the first follow-up visit (n=44), the probability of change to negative rose from 0 to 0.78 between 7 and 21 months after treatment. For HPV-negative patients (n=47), the probability of change to positive rose to 0.13 between 9 and 26 months. After a median follow-up of 50 months (range, 2-80), the NPV for CIN2+ was 1.00. The PPV was 0.60 (95% confidence interval, 0.43-0.77) after 26 months. The median time to detection was 5 months. CONCLUSIONS: If adequately confirmed, these findings would indicate that HPV testing is capable to identify the patients who have had their lesions fully removed, and would make it possible to focus follow-up efforts on a subset of patients at high risk of residual or progressive disease.

Accuracy of Colposcopically Directed Biopsy: Results from an Online Quality Assurance Programme for Colposcopy in a Population-Based Cervical Screening Setting in Italy.

PURPOSE: To report the accuracy of colposcopically directed biopsy in an internet-based colposcopy quality assurance programme in northern Italy. METHODS: A web application was made accessible on the website of the regional Administration. Fifty-nine colposcopists out of the registered 65 logged in, viewed a posted set of 50 digital colpophotographs, classified them for colposcopic impression and need for biopsy, and indicated the most appropriate site for biopsy with a left-button mouse click on the image. RESULTS: Total biopsy failure rate, comprising both nonbiopsy and incorrect selection of biopsy site, was 0.20 in CIN1, 0.11 in CIN2, 0.09 in CIN3, and 0.02 in carcinoma. Errors in the selection of biopsy site were stable between 0.08 and 0.09 in the three grades of CIN while decreasing to 0.01 in carcinoma. In multivariate analysis, the risk of incorrect selection of biopsy site was 1.97 for CIN2, 2.52 for CIN3, and 0.29 for carcinoma versus CIN1. CONCLUSIONS: Although total biopsy failure rate decreased regularly with increasing severity of histological diagnosis, the rate of incorrect selection of biopsy site was stable up to CIN3. In multivariate analysis, CIN2 and CIN3 had an independently increased risk of incorrect selection of biopsy site.

The SUMO conjugating enzyme UBC9 as a biomarker for cervical HPV infections.

Human papillomaviruses (HPVs) infect stratified epithelium and are the causative agents of cervical cancer, the second most common cause of cancer-related death in women. A critical aspect that still persists in the HPV field is the selection of very sensitive and specific HPV diagnostic assays. Here, we provide evidence that the crucial small ubiquitin-like modifier (SUMO) E2-conjugating enzyme Ubc9 is strongly upregulated in cervical lesions. Ubc9 detection could thus be used in diagnosing and/or monitoring the progression of an HPV oncogenic infection.

Prospective evaluation of p16/Ki-67 dual-stained cytology for managing women with abnormal Papanicolaou cytology: PALMS study results.

BACKGROUND: Testing for the presence of the human papillomavirus (HPV) is widely accepted for triaging Papanicolaou cytology results categorized as atypical squamous cells of undetermined significance (ASC-US). In contrast, HPV testing has limited use in triaging cytological low-grade squamous intraepithelial lesions (LSILs) due to prevalence rates of typically >80%. In the current study, the authors assessed the diagnostic performance of p16/Ki-67 dual-stained cytology in triaging ASC-US and LSIL cases within the prospective, multicentric Primary ASC-US LSIL Marker Study (PALMS). METHODS: A total of 575 ASC-US cases and 529 LSIL cases from a cohort of 27,349 women who were prospectively enrolled into the PALMS study in 5 European countries were tested with p16/Ki-67 dual-stained cytology and Hybrid Capture 2 (HC2) HPV testing. Colposcopy-guided biopsy results of cervical intraepithelial neoplasia of grade 2 or worse (CIN2+) were used as clinical endpoints. RESULTS: p16/Ki-67 dual-stained cytology demonstrated comparable (ASC-US: 94.4% for dual-stained cytology vs 100% for HC2 testing; P = .317) or lower (LSIL: 85.7% for dual-stained cytology vs 98.4% for HC2 testing; P = .005) sensitivity for CIN2+, but higher levels of specificity compared with HC2 HPV testing in both ASC-US (78.7% vs 60.4%; P<.001) and LSIL (53.3% vs 15.6%; P<.001) cases. Positive predictive values for CIN2+ were substantially higher for dual-stained cytology versus HC2 HPV testing, especially in LSIL, and in ASC-US cases for women aged <30 years. CONCLUSIONS: The clinical usefulness and efficiency of triaging women with ASC-US or LSIL Papanicolaou cytology results by p16/Ki-67 dual-stained cytology testing has been confirmed in this prospective, pan-European study. The high positive predictive value of dual-stained cytology for the presence of high-grade CIN may help to reduce the number of unnecessary colposcopy referrals.

Relevance of random biopsy at the transformation zone when colposcopy is negative.

OBJECTIVE: A post hoc analysis to determine the diagnostic yield of random biopsy in detecting high-grade cervical disease in women with negative colposcopy. METHODS: The ATHENA (Addressing the Need for Advanced HPV Diagnostics) trial screened more than 47,000 women with cytology and high-risk human papillomavirus (HPV) DNA genotyping. Colposcopy was performed in all women with abnormal cytology or positive HPV results. A single random biopsy was taken at the squamocolumnar junction if colposcopy was adequate and no lesions were identified. RESULTS: The random biopsy diagnosed 20.9% (81/388, 95% confidence interval [CI] 16.9-25.3%) and 18.9% (45/238, 95% CI 14.1-24.5%) of the total cervical intraepithelial neoplasia (CIN) grade 2 or worse and grade 3 or worse, respectively. This additional disease was detected in both HPV 16 or 18+ and for 12 other high-risk HPV+ women. For HPV 16 or 18, the absolute risk for detection of CIN 2 or worse on random biopsy in the overall population was 13.1% (40/305, 95% CI 9.8-17.4%) and 8.2% (25/305, 95% CI 5.6-11.8%) for CIN 3 or worse. By contrast, the absolute risk for 12 other high-risk HPV+ women was 3.5% (29/820, 95% CI 2.5-5%) and 1.7% (14/820, 95% CI 1.0-2.8%) for CIN 2 or worse and CIN 3 or worse, respectively. CONCLUSION: A single random biopsy increased the detection of high-grade disease when no lesions were visualized at colposcopy. The absolute risks of disease associated with the random biopsy were highest for women positive for genotype 16 or 18. Our study supports performing a random biopsy in women undergoing colposcopy without visible lesions, particularly in those positive for HPV 16 or 18. LEVEL OF EVIDENCE: : II.

Prognostic value of human papillomavirus in anal squamous cell carcinoma.

PURPOSE: Anal cancer is an uncommon malignancy, but its incidence is increasing worldwide. Chemoradiation is the standard primary treatment for patients with loco-regional limited disease. However, once patients develop metastatic spread, the prognosis is very poor. Human papillomavirus (HPV) is present in around 80 % of anal cancers, but its prognostic and/or predictive value is essentially unknown in this disease. METHODS: We retrospectively evaluated 50 patients with the diagnosis of anal squamous cell carcinoma treated at our institution with combined chemoradiotherapy for loco-regional limited disease. HPV status was evaluated from paraffin-embedded tumor tissues collected at the time of diagnosis by a polymerase chain reaction analysis. RESULTS: Among 50 patients, 42 (84 %) were HPV-positive. Thirty-two (64 %) patients were positive to genotype 16, two (4 %) to genotype 18, and three (6 %) to both 16 and 18. Lymph nodal involvement and clinical stage at diagnosis were more advanced for HPV-positive patients. After a median follow-up of 4 years (range 0.4-13.8), 46 (92 %) patients were alive. Overall, eight patients relapsed: One regional, one loco-regional, and six distant recurrences were observed. Four patients died of metastatic disease. Five-year disease-free survival (DFS) in HPV-positive and HPV-negative patients was 92.5 and 50.0 %, respectively (P < 0.01). In multivariate analysis, HPV-positivity was associated with a statistically significant better 5-year DFS (HR HPV+ vs HPV- 0.10; 95 % CI 0.02-0.50). Five-year overall survival in HPV-positive and HPV-negative patients was 93.3 and 66.7 %, respectively (P = 0.12). CONCLUSIONS: In our study, HPV-positive anal cancers had a statistically significant improved DFS compared to HPV-negative group.

An online quality assurance program for colposcopy in a population-based cervical screening setting in Italy: results on colposcopic impression.

OBJECTIVE: To report the results of an Internet-based colposcopy quality assurance program from a population-based cervical screening service in a large region of northern Italy. METHODS: In 2010 to 2011, a Web application was made accessible on the Web site of the regional administration. Fifty-nine colposcopists of the registered 65 participated. They logged-in, viewed a posted set of 50 high-quality digital colpophotographs selected by an expert committee, and rated them for colposcopic impression using a 4-tier classification (Negative; abnormal, grade 1 [G1]; abnormal, grade 2 [G2]; suspected invasive cancer [Cancer]) derived from the International Federation for Cervical Pathology and Colposcopy 2002 classification. kappa (κ) coefficients for intercolposcopist agreement and colposcopist-committee agreement were calculated. RESULTS: Colposcopist-committee agreement was greater than intercolposcopist agreement (overall κ 0.69 vs 0.60, p<.001). The κ values for colposcopist-committee agreement were 0.83 on Negative, 0.53 on G1, 0.66 on G2, and 0.80 on Cancer (all p values for pairwise comparisons<.001, except for Negative vs Cancer [p=.078]). There was no systematic tendency for colposcopists to underestimate or overestimate the colposcopic findings (2-tailed sign test, p=.13). Overall colposcopist-committee agreement was greater among patients 35 years or older (p<.001) and for colposcopists with previous quality assurance experiences (p<.01). Only 0.2% of Negative impressions were formulated for a cervical intraepithelial neoplasia grade 2 or worse. As a parallel finding, the impression of Cancer predicted cervical intraepithelial neoplasia grade 2 or less in 0.5% of cases. The histologic substrates of G1 were dispersed over a large spectrum. CONCLUSIONS: The reproducibility of colposcopic impression, when classified by trained colposcopists examining high-quality images, is higher than is generally thought.

Performance of self-sampled HPV test in comparison with liquid based cytology.

OBJECTIVE: Strong evidences shows that HPV testing is more sensitive than cytology in detecting high-grade CIN. HPV test can be performed on samples collected by women themselves by means of self-sampling devices. This study compares the results of self-sampled HPV tests with the results of liquid based cytology (LBC). STUDY DESIGN: Seven hundred women scheduled for cervical cytology self-collected a cervicovaginal sample for HPV testing and then underwent a clinician-collected LBC at the European Institute of Oncology. The HPV and LBC results were compared with the McNemar test. RESULTS: All HSIL (N=5) resulted hrHPV positive. LBC resulted LSIL or worse in 38 (5.4%) women (out of 700). Self-sampled HPV was positive in 96 women (13.7%). A LSIL or worse LBC result was found in 15 (2.5%) patients, out of the 604 hrHPV negative women and in 23 (24%) patients, out of the 96 hrHPV positive women. Positive cytology after a self-sampled HPV positive result had an Odds Ratio of 12.4 (95% CI: 5.8-26.6). CONCLUSION: Self-collected HPV testing identifies a group of women at high risk of positive LBC and high grade SIL.

Tissue genotyping of 37 in situ and invasive cervical cancer with a concomitant negative HC2 HPV DNA test.

OBJECTIVE: The rare occurrence of histology-proven cervical intraepithelial neoplasia grade 3 (CIN 3) or invasive cancer with a negative HC2 result is known. Tissue blocks of 37 cases of histology-diagnosed CIN 3+ with a concomitant negative HC2 test were genotyped to investigate the human papillomavirus (HPV) status within the lesion. METHODS: We considered 1,976 cervical excision specimens performed with concomitant HC2 test. Of these, 37 histology-confirmed CIN 3+ resulted HC2 negative. Thirty-three paraffin blocks, derived by the cervical excision, could be genotyped for high- (HR) and low-risk (LR) HPV genotypes. RESULTS: Detailed histology showed 30 CIN 3, 2 squamous cell invasive carcinomas, and 5 invasive adenocarcinomas. One specimen resulted not amplifiable at the genotyping. Twenty-two cases (68.7%) were positive for HR-HPV types, either in single (n = 17) or multiple HR-HPV infection (n = 5). Most of the HR-HPVs found were 16 or 18. Ten cases (31.3%) were negative for HR-HPV types; 5 of these were positive for probable HR-HPV types, not detectable with HC2 HR-probes, 1 was positive to LR-HPV types, while 1 had HPV-69/71. Three cases were negative for HPV DNA, either high or low risk. CONCLUSIONS: Of the rare cases of CIN 3+ lesions with concomitant negative HC2 test, 69% are true failures in HR-HPV detection. One third of HC2-negative CIN 3+ is related to the presence of other HPV genotypes not covered by the HC2 panel or to undetectable HPV in the lesion; both these rare occurrences were already described in large cancer series and partially explain the occurrence of HPV-negative CIN 3+.

Screening for cervical cancer precursors with p16/Ki-67 dual-stained cytology: results of the PALMS study.

BACKGROUND: Pap cytology is known to be more specific but less sensitive than testing for human papillomavirus (HPV) for the detection of high-grade cervical intraepithelial neoplasia (CIN2+). We assessed whether p16/Ki-67 dual-stained cytology, a biomarker combination indicative of transforming HPV infections, can provide high sensitivity for CIN2+ in screening while maintaining high specificity. Results were compared with Pap cytology and HPV testing. METHODS: A total of 27,349 women 18 years or older attending routine cervical cancer screening were prospectively enrolled in five European countries. Pap cytology, p16/Ki-67 immunostaining, and HPV testing were performed on all women. Positive test results triggered colposcopy referral, except for women younger than 30 years with only positive HPV test results. Presence of CIN2+ on adjudicated histology was used as the reference standard. Two-sided bias-corrected McNemar P values were determined. RESULTS: The p16/Ki-67 dual-stained cytology positivity rates were comparable with the prevalence of abnormal Pap cytology results and less than 50% of the positivity rates observed for HPV testing. In women of all ages, dual-stained cytology was more sensitive than Pap cytology (86.7% vs 68.5%; P < .001) for detecting CIN2+, with comparable specificity (95.2% vs 95.4%; P = .15). The relative performance of the tests was similar in both groups of women: younger than age 30 and 30 years or older. HPV testing in women 30 years or older was more sensitive than dual-stained cytology (93.3% vs 84.7%; P = .03) but less specific (93.0% vs 96.2%; P < .001). CONCLUSIONS: The p16/Ki-67 dual-stained cytology combines superior sensitivity and noninferior specificity over Pap cytology for detecting CIN2+. It suggests a potential role of dual-stained cytology in screening, especially in younger women where HPV testing has its limitations.

Comparison of the performance of carcinogenic HPV typing of the Roche Linear Array and Qiagen LiquiChip® HPV assays.

BACKGROUND: Cervical cancer is caused by high-risk types of human papillomavirus (HPV). DNA testing of such high-risk types of HPV could improve cervical screening.The aim of the study was to compare the sensitivities and positive predictive values of two commercially available typing assays (Qiagen LQ and Roche LA) and to comparatively assess the distribution of HPV types with these two assays. METHODS: The study population comprised 311 ASCUS + women with abnormal pap tests who were HCII positive and who were admitted to three European referral gynecology clinics between 2007 and 2010 (Madrid, Marseille and Milan). All patients underwent LQ and LA tests. RESULTS: The sensitivity of the two assays for HPV typing was 94% for LQ and 99% for LA (compared with HCII). The overall concordance between LQ and LA was 93%. The three prevalent genotypes, HPV16, HPV18, and HPV31, were identified with a high concordance using the two assays: kappa 0.93, 0.83, and 0.91, respectively. Mixed genotypes were more frequently detected by LA than by LQ: 52% vs. 18%, respectively (p < .0001). CONCLUSIONS: These assays have a good clinical sensitivity for detecting HPV types in CIN2+ patients and allow the virus type to be detected in the same experiment. Our study revealed no significant difference between LQ and LA for CIN2+ or CIN3+ diagnosis, indicating similar distributions of HPV types and a mixed genotype detection that is higher for LA than for LQ.

Rationale and development of an on-line quality assurance programme for colposcopy in a population-based cervical screening setting in Italy.

BACKGROUND: Colposcopy, the key step in the management of women with abnormal Pap smear results, is a visual technique prone to observer variation, which implies the need for prolonged apprenticeship, continuous training, and quality assurance (QA) measures. Colposcopy QA programmes vary in level of responsibility of organizing subjects, geographic coverage, scope, model, and type of actions. The programmes addressing the clinical standards of colposcopy (quality of examination and appropriateness of clinical decisions) are more limited in space and less sustainable over time than those focused on the provision of the service (resources, accessibility, etc.). This article reports on the protocol of a QA programme targeting the clinical quality of colposcopy in a population-based cervical screening service in an administrative region of northern Italy. METHODS/DESIGN: After a situation analysis of local colposcopy audit practices and previous QA initiatives, a permanent web-based QA programme was developed. The design places more emphasis on providing education and feedback to participants than on testing them. The technical core is a log-in web application accessible on the website of the regional Administration. The primary objectives are to provide (1) a practical opportunity for retraining of screening colposcopists, and (2) a platform for them to interact with colposcopists from other settings and regions through exchange and discussion of digital colposcopic images. The retraining function is based on repeated QA sessions in which the registered colposcopists log-in, classify a posted set of colpophotographs, and receive on line a set of personal feedback data. Each session ends with a plenary seminar featuring the presentation of overall results and an interactive review of the test set of colpophotographs. This is meant to be a forum for an open exchange of views that may lead to more knowledge and more diagnostic homogeneity. The protocol includes the criteria for selection of colpophotographs and the rationale for colposcopic gold standards. DISCUSSION: This programme is an ongoing initiative open to further developments, in particular in the area of basic training. It uses the infrastructure of the internet to give a novel solution to technical problems affecting colposcopy QA in population-based screening services.