HPV vaccination and cervical screening: the knowledge and attitudes of mothers of adolescent girls.

OBJECTIVE: Mothers play a significant role in decision making about human papillomavirus (HPV) vaccination for their daughters and about cervical screening attendance for themselves. This study had three objectives, to explore: (1) mothers' knowledge and attitudes about HPV and HPV vaccination, (2) their knowledge and attitudes about cervical cancer and screening, and (3) whether their daughter's HPV vaccination invitation was an opportunity to nudge mothers to attend screening. DESIGN: 138 women from North Staffordshire completed a cross-sectional survey and 15 took part in follow-up focus groups. RESULTS: Despite high self-reported engagement with both the cervical screening and HPV vaccination programmes, relatively low levels of knowledge and some uncertainty were evident. There was mixed opinion about the potential of using the vaccination invite as an opportunity to nudge mothers to attend cervical screening. CONCLUSION: Even amongst women who do engage positively with the programmes, knowledge is not as complete and certain as it could be. Further research is needed with women who are less likely to accept the vaccination for their daughters. Women need to be better informed, which may go some way to reversing the decline in screening and maintaining high levels of vaccination.

EBCOG position statement: Gender neutral HPV vaccination for young adults.

Human Papilloma Virus (HPV) has been implicated in the initiation of several types of cancers in both females and males. Therefore, it is imperative that national immunization programs should ensure that both young women and young men receive full immunization for herd immunity in their teenage years. A recent review confirmed that vaccination of boys and girls would be most cost-effective under the circumstances that both individual costs and coverage are low. By doing so, it would be possible to reduce the incidence of HPV-related malignancies to a large extent at later age in both sexes.

Barriers and motivators for uptake of cervical cancer prevention strategies in Eastern Europe: the perspective from Latvia.

INTRODUCTION: The incidence of cervical cancer (CC) in eastern European countries is high; however, uptake of available prevention strategies is suboptimal. We explored knowledge, behaviors, and attitudes toward CC prevention strategies in Latvian women. METHODS: A mixed-methods study of Latvian women, consisting of surveys and semi-structured interviews, was conducted in Riga, Latvia in September and October 2015. RESULTS: Altogether, 158 surveys were completed and 10 interviews were conducted. In total, 87% (n = 135) had previously had a smear test, and 67% (n = 105) correctly identified that cervical cytology was performed to identify precancerous changes. The practice of annual gynecological checkups was prevalent, and many believed it to be synonymous with cervical screening. Detailed knowledge of human papillomavirus (HPV) infection and the HPV vaccine was deficient, although 73% (n = 115) and 70% (n = 90), respectively, claimed to have heard of them. Negative attitudes existed regarding the HPV vaccine due to fear of potential side effects. On learning that HPV was transmitted through sexual contact, the notion of testing positive for HPV was met with shame and embarrassment. CONCLUSIONS: A small proportion of Latvian women are over-screened, whereas many women remain unscreened. The main contributing factor for this was their poor understanding of the roles that cervical screening and HPV vaccination play in preventing CC.

2017 update of the European Federation for Colposcopy (EFC) performance standards for the practice of colposcopy.

A refinement of quality indicators (QIs) is described whereby the quality of care can be measured across colposcopy services in different countries and healthcare settings. A five-round Delphi process was conducted at successive satellite meetings from 2011 to 2015 of leading European colposcopists to refine the most high-scoring QIs relevant to colposcopic practice. A review and refinement of the wording of the standards and their criteria was undertaken by national society representatives. Six quality indicators were identified and refined. "Documentation of whether the squamocolumnar junction (SCJ) has been visible or not" was changed into "for cervical colposcopy transformation zone (TZ) type (1, 2 or 3) should be documented". The standard "percentage of cases having a colposcopic examination prior to treatment for abnormal cytology" was changed to "percentage of cases having a colposcopic examination prior to treatment for abnormal cervical screening test". The standard "percentage of all excisional treatments/conizations containing CIN2+ (cervical intra-epithelial neoplasia grade two or worse)" was changed into "percentage of excisional treatments/conizations having a definitive histology of CIN2+. Definitive histology is highest grade from any diagnostic or therapeutic biopsies". The standard "percentage of excised lesions/conizations with clear margins" was unchanged. The remaining two QIs define the minimum caseloads required for colposcopists. However, "cytology" was replaced by "screening results" to acknowledge the introduction of human papillomavirus testing to European screening programmes. Six QIs were identified to define good practice in colposcopy.

Incomplete excision of cervical precancer as a predictor of treatment failure: a systematic review and meta-analysis.

BACKGROUND: Incomplete excision of cervical precancer is associated with therapeutic failure and is therefore considered as a quality indicator of clinical practice. Conversely, the risk of preterm birth is reported to correlate with size of cervical excision and therefore balancing the risk of adequate treatment with iatrogenic harm is challenging. We reviewed the literature with an aim to reveal whether incomplete excision, reflected by presence of precancerous tissue at the section margins, or post-treatment HPV testing are accurate predictors of treatment failure. METHODS: We did a systematic review and meta-analysis to assess the risk of therapeutic failure associated with the histological status of the margins of the tissue excised to treat cervical precancer. We estimated the accuracy of the margin status to predict occurrence of residual or recurrent high-grade cervical intraepithelial neoplasia of grade two or worse (CIN2+) and compared it with post-treatment high-risk human papillomavirus (HPV) testing. We searched for published systematic reviews and new references from PubMed-MEDLINE, Embase, and CENTRAL and did also a new search spanning the period Jan 1, 1975, until Feb 1, 2016. Studies were eligible if women underwent treatment by excision of a histologically confirmed CIN2+ lesion, with verification of presence or absence of CIN at the resection margins; were tested by cytology or HPV assay between 3 months and 9 months after treatment; and had subsequent follow-up of at least 18 months post-treatment including histological confirmation of the occurrence of CIN2+. Primary endpoints were the proportion of positive section margins and the occurrence of treatment failure associated with the marginal status, in which treatment failure was defined as occurrence of residual or recurrent CIN2+. Information about positive resection margins and subsequent treatment failure was pooled using procedures for meta-analysis of binomial data and analysed using random-effects models. FINDINGS: 97 studies were eligible for inclusion in the meta-analysis and included 44 446 women treated for cervical precancer. The proportion of positive margins was 23·1% (95% CI 20·4-25·9) overall and varied by treatment procedure (ranging from 17·8% [12·9-23·2] for laser conisation to 25·9% [22·3-29·6] for large loop excision of the transformation zone) and increased by the severity of the treated lesion. The overall risk of residual or recurrent CIN2+ was 6·6% (95% CI 4·9-8·4) and was increased with positive compared with negative resection margins (relative risk 4·8, 95% CI 3·2-7·2). The pooled sensitivity and specificity to predict residual or recurrent CIN2+ was 55·8% (95% CI 45·8-65·5) and 84·4% (79·5-88·4), respectively, for the margin status, and 91·0% (82·3-95·5) and 83·8% (77·7-88·7), respectively, for high-risk HPV testing. A negative high-risk HPV test post treatment was associated with a risk of CIN2+ of 0·8%, whereas this risk was 3·7% when margins were free. INTERPRETATION: The risk of residual or recurrent CIN2+ is significantly greater with involved margins on excisional treatment; however, high-risk HPV post-treatment predicts treatment failure more accurately than margin status. FUNDING: European Federation for Colposcopy and Institut national du Cancer (INCA).

Psycho-social influences upon older women's decision to attend cervical screening: A review of current evidence.

Cervical cancer is the fourth most common cancer in women worldwide (WHO, 2016). In many developed countries the incidence of cervical cancer has been significantly reduced by the introduction of organised screening programmes however, in the UK, a fall in screening coverage is becoming a cause for concern. Much research attention has been afforded to younger women but age stratified mortality and incidence data suggest that older women's screening attendance is also worthy of study. This paper provides a review of current evidence concerning the psycho-social influences that older women experience when deciding whether to attend cervical screening. Few studies have focussed on older women and there are significant methodological issues with those that have included them in their samples. Findings from these studies indicate several barriers which may deter older women from screening, such as embarrassment and logistical issues. Drivers to screening include reassurance and a sense of obligation. Physical, social and emotional changes that occur as women age may also have an impact on attendance. This review concludes that there is a clear need for better understanding of the perceptions of older women specifically with regard to cervical cancer and screening. Future research should inform the design of targeted interventions and provision of information to enable informed decision-making regarding cervical screening among older women.

Awareness of HPV infection and attitudes toward HPV vaccination among Latvian adolescents.

OBJECTIVE: To evaluate awareness of HPV and its vaccine among Latvian adolescents. METHODS: A cross-sectional survey was conducted in a 2-week period in September 2015 among 270 adolescents attending a secondary school in Riga, Latvia. All students present during sexual-health classes (grades 10-12 [aged 16-21 years]) were included. A self-administered paper-based survey assessed sociodemographic factors, sexual behaviours, smear history and knowledge of sexually transmitted infections, HPV and HPV vaccine knowledge, and sources of information. RESULTS: Overall, 121 surveys were completed (62 by male students and 59 by female students). Latvian adolescents lacked awareness of HPV: only 26 (21.5%) had heard of HPV (21 [35.6%] female students vs 5 [8.1%] male students; P<0.001) and 12 (9.9%) of the HPV vaccine. Eighty (66.1%) participants felt inadequately informed about HPV. However, the adolescents partook in high-risk behaviours: 70 (57.9%) students were sexually active, 26 (37.1%) of whom had already had three or more sexual partners. CONCLUSION: Despite the high prevalence of HPV in Latvia, poor knowledge about HPV infection among adolescents could explain low uptake of the HPV vaccine by this high-risk population. Therefore, educational strategies that highlight the consequences of HPV could promote acceptance of vaccination.

The Use of the Colposcopically Directed Punch Biopsy in Clinical Practice: A Survey of British Society of Colposcopy and Cervical Pathology (BSCCP)-Accredited Colposcopists.

OBJECTIVES: The colposcopically directed punch biopsy has been an integral component of colposcopic practice. In light of the changing landscape of the cervical screening programme, a study was conducted to investigate the current practice of British Society of Colposcopy and Cervical Pathology-accredited colposcopists on technique and rationale for performing a punch biopsy. MATERIALS AND METHODS: A web-based questionnaire survey was e-mailed to all British Society of Colposcopy and Cervical Pathology-accredited colposcopists. Questions included selection criteria for performing a punch biopsy, number of biopsies, and technique. Results were analyzed by specialty, experience, and workload. RESULTS: A total of 749 colposcopists responded, 50.2% of the 1,493 total. The respondents were obstetrician and gynecologists (42.9%), gynecologists/oncologists (33.6%), and nurse colposcopists (19.8%). Most colposcopists (78.3%) had more than 5-year colposcopy experience and saw in excess of 11 new cases (73.4%) of abnormal cervical cytology/month. Most colposcopists (56%) aimed to take 2 biopsies to diagnose cervical intraepithelial neoplasia, and very few (16.2%) reported routinely taking random biopsies from normal areas of cervix. Looking at the trends in management in the case scenarios, there was a lower threshold for performing punch biopsy before large loop excision of the transformation zone in younger (age, <25 years) or nulliparous women versus older women (age, >40 years; p < .05). Colposcopists were more likely to take biopsies in women with low-grade cytology/colposcopic findings (71.2%, always or most of the times) as compared with high-grade cytology/colposcopic findings (40.3%, never or rarely). CONCLUSIONS: Colposcopically directed punch biopsy is routinely used by colposcopists; however, techniques, number of biopsies taken, and rationale for performing a biopsy vary greatly between colposcopists.

Colposcopists' experiences of HPV Test of Cure for the follow up of cervical intra-epithelial neoplasia.

OBJECTIVE: To survey lead colposcopists in England to explore their views on the recently introduced HPV Test of Cure (TOC) following treatment for cervical intra-epithelial neoplasia (CIN) and to determine the extent to which it has impacted their clinical practice and affected their patients. METHODS: An online survey was sent to lead colposcopists across England. Questions were asked focusing on the clinicians' confidence in the ability of TOC to guide follow up in various clinical scenarios and how the implementation of TOC had changed patient management. RESULTS: There was a 50% (N=88) response rate. 90% of respondents indicated they were happy with the new procedure. In the follow-up questions, 20% indicated they were uncomfortable with the procedure when it was applied to women who were CIN2+ with incomplete excision at the endocervical margin. Open-ended questions elicited positive aspects of TOC including reduced follow-up, increased reassurance for patients and clinicians and a faster return to the call-recall system. Negative observations included concerns around HPV positive cases, possible false negatives and anxiety in those women who were originally subject to the pre-TOC guidelines and were now returned to call-recall "earlier" than originally indicated to them. 11% of respondents also indicated they work around the new guidelines to some extent. CONCLUSION: Although clinicians are on the whole positive towards the introduction of TOC, concerns were raised which centre primarily around those patients with CIN2+ combined with positive endocervical margins, issues related to HPV positive cases and the possibility of a false negative HPV result. The possibility of patient anxiety due to return to routine screening earlier than originally expected was also identified as a concern.

The BH3 Mimetic Obatoclax Accumulates in Lysosomes and Causes Their Alkalinization.

Obatoclax belongs to a class of compounds known as BH3 mimetics which function as antagonists of Bcl-2 family apoptosis regulators. It has undergone extensive preclinical and clinical evaluation as a cancer therapeutic. Despite this, it is clear that obatoclax has additional pharmacological effects that contribute to its cytotoxic activity. It has been claimed that obatoclax, either alone or in combination with other molecularly targeted therapeutics, induces an autophagic form of cell death. In addition, obatoclax has been shown to inhibit lysosomal function, but the mechanism of this has not been elucidated. We have evaluated the mechanism of action of obatoclax in eight ovarian cancer cell lines. Consistent with its function as a BH3 mimetic, obatoclax induced apoptosis in three cell lines. However, in the remaining cell lines another form of cell death was evident because caspase activation and PARP cleavage were not observed. Obatoclax also failed to show synergy with carboplatin and paclitaxel, chemotherapeutic agents which we have previously shown to be synergistic with authentic Bcl-2 family antagonists. Obatoclax induced a profound accumulation of LC-3 but knockdown of Atg-5 or beclin had only minor effects on the activity of obatoclax in cell growth assays suggesting that the inhibition of lysosomal function rather than stimulation of autophagy may play a more prominent role in these cells. To evaluate how obatoclax inhibits lysosomal function, confocal microscopy studies were conducted which demonstrated that obatoclax, which contains two basic pyrrole groups, accumulates in lysosomes. Studies using pH sensitive dyes demonstrated that obatoclax induced lysosomal alkalinization. Furthermore, obatoclax was synergistic in cell growth/survival assays with bafilomycin and chloroquine, two other drugs which cause lysosomal alkalinization. These studies explain, for the first time, how obatoclax inhibits lysosomal function and suggest that lysosomal alkalinization contributes to the cytotoxic activity of obatoclax.

The Effect of Country of Birth on the Pattern of Disease and Survival From Cervical Cancer.

OBJECTIVE: The aim of the study was to investigate the impact of country of birth on the pattern of disease and survival from cervical cancer in women living in the United Kingdom. MATERIALS AND METHODS: A retrospective database evaluation study was performed to review all cases of cervical cancer diagnosed in the Pan-Birmingham Cancer Network between 2005 and 2009. Population characteristics and survival data were obtained from the West Midlands Cancer Registry and National Health Authority Information System, United Kingdom. Women's country of birth was classified as being high- (including patients born in the United Kingdom and Ireland), middle-, or low-income countries according to the World Bank country classification. Screening histories data were obtained from the West Midlands Cancer Screening Quality Assurance Reference Centre. Overall survival data were analyzed using the nonparametric Kaplan-Meier method with log-rank tests to compare between groups. RESULTS: Four hundred eighty-four cases were identified. A country of birth was available for 459 cases (94.8%). Cancers detected through screening or interval cancers accounted for 140 (28.9%) of cases compared with 226 (46.7%) where women had not complied with screening. Of the women born outside of the United Kingdom/Ireland, 40 (59.7%) originated from low-income, 23 (34.3%) from middle-income, and 4 (6.0%) from high-income countries. Multivariate analysis identified age (p < .001) and stage (p < .001) at diagnosis as having a significant effect on survival, but no effect was seen from social deprivation (p = .18) or economic status of country of birth (p = .30). DISCUSSION: Country of birth is not an independent prognostic indicator for cervical cancer survival.

Success rate of cold coagulation for the treatment of cervical intraepithelial neoplasia: a retrospective analysis of a series of cases.

OBJECTIVE: To establish the cure rate at 1 year of patients who have undergone cold coagulation for the treatment of cervical intraepithelial neoplasia (CIN). DESIGN: Retrospective review of data for all patients at Shrewsbury and Telford NHS Trust who had undergone cold coagulation as part of their treatment for CIN between 2001 and 2011. Follow-up data up to December 2012 were analyzed. SETTING: Colposcopy Department, Shrewsbury and Telford NHS Trust, United Kingdom. POPULATION: Women undergoing cold coagulation for the treatment of CIN between 2001 and 2011, with cytologic follow-up until December 2012. METHODS: Patients were identified using a local colposcopy database. Data were obtained via the local histopathology reporting systems. Statistical analyses were performed using Stata/IC 10.1 software. MAIN OUTCOME MEASURES: Posttreatment cytology and whether subsequent treatment was required, with histology results. RESULTS: Data on 557 patients were collected and analyzed. Pre-cold coagulation treatment histologic findings were CIN 1 in 156 patients (28.01%), CIN 2 in 260 patients (46.68%), and CIN 3 in 141 patients (25.31%). The median length of time between cold coagulation treatment and first follow-up smear, used to calculate cure rates at around 1 year, was 406 days (interquartile range 123 days, range 169-3,116 days). The cure rate after cold coagulation was 95.7% at around 1 year. CONCLUSIONS: Cold coagulation has a cure rate comparable to that of excisional treatments such as large loop excision of the transformation zone and should be considered more widely in patients undergoing primary treatment for CIN, where there is no suspicion of invasive disease on history, examination and cytologic results.

HPV testing and vaccination in Europe.

Current cytology-based screening has a moderate sensitivity to detect cervical intraepithelial neoplasia grade 3 (CIN 3) and cervical cancer even in those states providing rigorous quality control of their cervical screening programs. The impact of vaccination against human papillomavirus (HPV) types 16 and 18 as well as the incorporation of HPV testing on the detection of CIN 3 and cancer is discussed. HPV testing used as a triage for atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesions, test of cure after treatment, and HPV-based primary screening may improve current cervical screening programs.HPV testing as a triage test for ASCUS seems to offer an improved sensitivity, with a similar specificity as compared to repeat cytology for diagnosing high-grade CIN and has been recommended throughout most EU states. HPV testing as a triage test for low-grade squamous intraepithelial lesions has a low specificity and is not recommended in most member states. HPV test of cure offers an improved sensitivity compared to cytology for women with persistent cervical precancer after treatment. HPV-based cervical cancer screening is more effective than screening with cytology. The effects of HPV-based screening depend on the organization of the program and on adherence to algorithms for screening triage. Otherwise, it is likely that HPV-based screening will increase the referral rate to colposcopy including more women with no detectable cervical lesion. HPV vaccination will require many years to evaluate any beneficial effects on cervical cancer incidence and mortality.

The future role for colposcopy in Europe.

Improvements in the performance of cervical screening may be limited by the diagnostic performance of colposcopy. Nonetheless, colposcopy remains the best available tool to assess women considered at high risk for having or developing cervical cancer. The provision and role of colposcopy across Europe is variable. Introduction of vaccination against human papillomavirus (HPV) types 16 and 18 as well as the possible switch to HPV-based screening is likely to change the profiles of women presenting to colposcopy services and provide management difficulties for the colposcopist.The standard of colposcopy in Europe can be maintained or improved despite a variable availability of screening. The prevalence of cervical intraepithelial neoplasia grade 3 may decrease for women having had HPV vaccination. The incidence of cervical intraepithelial neoplasia grade 3 and cervical cancer in second and subsequent rounds of HPV-based screening are likely to decrease compared to cytology-based screening. In HPV-based screening, the numbers of women with no detectable or minor abnormalities at colposcopy and with screen-detected glandular disease are likely to increase. We have considered how these issues will affect states that have varying implementation of organized cervical screening programs and varying degrees of implementation of HPV testing or vaccination.The development of quality assurance across Europe accompanying these program changes is discussed.

European Federation of Colposcopy quality standards Delphi consultation.

OBJECTIVE: Optimization of colposcopy practice requires a program of quality assurance including the monitoring of performance indicators. The European Federation of Colposcopy (EFC) aimed to identify a list of quality indicators for colposcopic practice, which are relevant, reproducible and practical across all of the member countries. STUDY DESIGN: A five-round Delphi consultation was conducted in 30 full, 5 associate and 4 potential member countries in order to determine a core list of quality indicators including optimal target ranges. RESULTS: Six indicators were selected from a list of 37 proposed standards. Two further rounds of consultation were conducted to determine expert opinion on the target level for each of the standards. The six indicators identified and corresponding targets were: documentation of whether or not the squamocolumnar junction has been seen (100%); colposcopy prior to treatment for abnormal cervical cytology (100%); percentage of excisional treatments/conizations to contain cervical intra-epithelial neoplasia grade two or worse (≥85%); percentage of excised lesions/conizations with clear margins (≥80%); and two indicators concerned the number of cases to be colposcoped per year: ≥50 low-grade/minor and ≥50 high-grade/major cytological abnormalities. CONCLUSIONS: A Delphi consultation identified six EFC quality indicators. These are a first step in an international attempt to optimize colposcopy practice throughout Europe. The current targets are based on expert opinion and may need adaptation in the future. Data are needed from European colposcopy settings to determine whether the indicators are achievable practice-based benchmarks and will help in improving and fine tuning the list of performance indicators and targets.

Navitoclax augments the activity of carboplatin and paclitaxel combinations in ovarian cancer cells.

OBJECTIVES: To evaluate the efficacy of combination of navitoclax, carboplatin and paclitaxel in ovarian cancer. METHODS: 8 ovarian cancer cell lines were treated with either doublet or triplet combinations of navitoclax, carboplatin and paclitaxel. Interactions were assessed by determining a combination index or measuring caspase activity. The effect of the combinations was also evaluated by measuring the inhibition of cells grown as spheroids. RESULTS: Navitoclax exhibited modest (IC(50)=3-8 µM) single agent potency. Antagonism between carboplatin and paclitaxel was evident in Ovcar-4, Ovcar-8 and Skov-3 cells. Drug combinations including navitoclax with carboplatin and/or paclitaxel showed significantly less antagonism, or even synergy, in several cell lines than carboplatin/paclitaxel alone. Navitoclax enhanced the activation of caspase 3/7 induced by carboplatin and/or paclitaxel in Igrov-1 cells. Combinations of navitoclax, carboplatin and paclitaxel showed more than additive activity against Igrov-1 spheroids. CONCLUSIONS: Navitoclax improves the activity of combinations of carboplatin and paclitaxel in vitro. Our observations, taken with other published data, provide a rationale for clinical trials of navitoclax in ovarian cancer in combination with chemotherapy.

Understanding sensitivity to BH3 mimetics: ABT-737 as a case study to foresee the complexities of personalized medicine.

BH3 mimetics such as ABT-737 and navitoclax bind to the BCL-2 family of proteins and induce apoptosis through the intrinsic apoptosis pathway. There is considerable variability in the sensitivity of different cells to these drugs. Understanding the molecular basis of this variability will help to determine which patients will benefit from these drugs. Furthermore, this understanding aids in the design of rational strategies to increase the sensitivity of cells which are otherwise resistant to BH3 mimetics. We discuss how the expression of BCL-2 family proteins regulates the sensitivity to ABT-737. One of these, MCL-1, has been widely described as contributing to resistance to ABT-737 which might suggest a poor response in patients with cancers that express levels of MCL-1. In some cases, resistance to ABT-737 conferred by MCL-1 is overcome by the expression of pro-apoptotic proteins that bind to apoptosis inhibitors such as MCL-1. However, the distribution of the pro-apoptotic proteins amongst the various apoptosis inhibitors also influences sensitivity to ABT-737. Furthermore, the expression of both pro- and anti-apoptotic proteins can change dynamically in response to exposure to ABT-737. Thus, there is significant complexity associated with predicting response to ABT-737. This provides a paradigm for the multiplicity of intricate factors that determine drug sensitivity which must be considered for the full implementation of personalized medicine.

Is the colposcopically directed punch biopsy a reliable diagnostic test in women with minor cytological lesions?

OBJECTIVE: The study aimed to determine the accuracy of the colposcopy-directed punch biopsy (punch) to detect or exclude high-grade cervical intraepithelial neoplasia (CIN 2 or 3) in women with atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesion (LSIL) cytological result and minor colposcopic findings. MATERIALS AND METHODS: In a diagnostic test accuracy study, women with ASCUS or LSIL cytological result and minor colposcopic changes had a single colposcopy-targeted punch biopsy was performed immediately followed by a loop electrocautery excision procedure (LEEP) biopsy. The trial was powered to detect a level of κ for a dichotomous outcome of 0.4 (i.e., fair-to-moderate agreement), with a two-sided significance level of 5% and a power of 90%. Accuracy parameters were computed using a cutoff for positive punch biopsy result of CIN 1+ and CIN 2+ for an outcome of CIN 2+ and CIN 3+ assessed in the LEEP specimen. RESULTS: Sixty-eight punch biopsy/LEEP-paired samples were analyzed. Of the 8 CIN 3 lesions, 6 and 4 were detected at cutoff CIN 1+ and CIN 2+, respectively (sensitivity, 50% and 75%). The corresponding specificities were 65% (39/60) and 97% (58/60). The punch biopsies identified only 14 (67%) or 6 (20%) of the 21 CIN 2+ lesions at cutoff CIN 1+ or CIN 2+, respectively. Of the punch biopsies, 31 (45.6%) accurately detected the severity of cervical abnormality. CONCLUSIONS: A single colposcopically directed punch biopsy appears to be insufficient to exclude underlying CIN 2 or 3.