Objectives Self-sampling may increase access to cervical cancer screening in low-resource settings. Using Xpert HPV, we compared test performance of self- and clinician-collected samples in HIV-positive and HIV-negative women in South Africa. Materials and Methods Three hundred thirty HIV-positive and 375 HIV-negative women in the screening group and 202 HIV-negative and 200 HIV-positive women in the referral group, aged 30–65 years, participated in the study. All women self-collected a vaginal sample, and then, a cervical sample was collected by a clinician (both tested using Xpert HPV), followed by colposcopic examination and collection of histologic specimens. Results There was good agreement between self- and clinician-collected samples for detection of any high-risk human papillomavirus (HPV, κ = 0.72 [95% CI = 0.669–0.771]). Prevalence of HPV and sensitivity of the test to detect cervical intraepithelial neoplasia 2+ was similar in self- and clinician-collected samples. Specificity was lower in self-collected than in clinician-collected samples in both HIV-negative (self: 77.5% [95% CI = 72.8–81.8] vs clinician: 86.9% [95% CI = 82.9–90.2]) and HIV-positive (self: 44.0% [95% CI = 38.0–50.1] vs clinician: 59.7% [95% CI = 53.6–65.6]) women. Restricting the definition of screen-positive to 3 of 5 channels on HPV Xpert improved specificity in both HIV-negative (self: 83.2% [95% CI = 78.8–87.0] vs clinician: 89.7% [95% CI = 86.1–92.7]) and HIV-positive (self: 54.2% [95% CI = 48.1–60.2] vs clinician: 67.4% [95% CI = 61.5–72.9]) women. Conclusions The self-collected sample had good agreement with the clinician-collected sample for the detection of HPV, and restricting the HPV types may improve the specificity in HIV-positive women.

There are marked global disparities in the incidence of cervical cancer, with most cases occurring in low-and middle-income countries (LMICs). In high-income countries (HICs), the implementation of organised cytology-based cervical screening programmes has resulted in a decline in cervical cancer incidence and mortality rates. Unfortunately, cervical cancer continues to be a significant public health problem in LMICs owing to the lack of high-quality screening programmes and poor screening coverage in those regions. [1,2] Effective cytology-based screening requires a relatively robust healthcare infrastructure with functional laboratory services, welltrained healthcare providers and technicians, good referral systems, and linkage to accessible treatment facilities and follow-up after treatment for women with abnormal screening tests. This approach requires resources typically not available in LMICs, hampering the initiation and maintenance of screening programmes. [3] The World Health Organization has recommended molecular testing for human papillomavirus (HPV) as an alternative to cytologybased screening in low-resource settings, given that these tests are more sensitive than cytology and visual inspection methods in detecting high-grade cervical intraepithelial neoplasia and cancer. [2,[4][5][6] A randomised controlled trial in India showed that in low-resource settings, a single round of HPV testing was associated with a significant reduction in cervical cancer mortality. [5] HPV tests also have the advantage that vaginal samples can be collected by the This open-access article is distributed under Creative Commons licence CC-BY-NC 4.0.

Several high-risk human papillomavirus (HPV)-induced cell biomarkers have been proposed as possible candidates to identify patients harboring high-grade squamous intraepithelial lesions (HSILs) of the uterine cervix. We aimed to determine the feasibility of the detection of the mRNA of six biomarkers in cervical smear specimens obtained by liquid-based cytology and to evaluate whether this approach might be useful in the identification of patients with HSIL. One-hundred and twenty three women referred to colposcopy in the Hospital Clinic of Barcelona were included in the study. After a thorough study, including Pap test, high-risk HPV testing (Hybrid Capture 2 test), and colposcopy with directed biopsy and/or endocervical curettage, 48 patients were diagnosed with HSIL, whereas 75 were classified as negative (n ¼ 28), or harboring low-grade SIL (n ¼ 47). CDKN2A/p16, BIRC5, MMP9, TOP2A, MCM5, and MKI67 mRNA expression was analyzed by reverse transcription quantitative polymerase chain reaction in liquid-based cytology after the Pap test and Hybrid Capture 2 performance. The tissue expression of these biomarkers was analyzed by immunohistochemistry in the biopsy material. One-hundred and thirteen out of 123 (92%) liquid-based cytology yielded adequate material for mRNA analysis. TOP2A was the most sensitive (97%) biomarker for the detection of HSIL and CDKN2A/p16 the most specific (78%). The combination of TOP2A and CDKN2A/p16 showed a sensitivity of 96% (95% confidence interval (CI): 88-99) and a specificity of 71% (95% CI: 55-82). In the immunohistochemistry analysis, all biomarkers showed a high sensitivity but low specificity for HSIL, except CDKN2A/p16 which had a sensitivity of 100% and a specificity of 63%. The combination of TOP2A and CDKN2A/p16 showed a sensitivity of 100% (95% CI: 91-100) and a specificity of 43% (95% CI: 32-55). The detection of mRNA of cell biomarkers in liquid-based cytology material is feasible. The combination TOP2A and CDKN2A/p16 has a good balance between sensitivity and specificity for the detection of women with HSIL. Modern Pathology (2015) 28, 312-320; doi:10.1038/modpathol.2014.106; published online 5 September 2014Screening programs based on cervical cytology (Pap test) have led to a decrease in the incidence and the mortality by cervical cancer. However, the efficacy of cytological screening is hampered by the suboptimal sensitivity and interobserver variability of the conventional Pap test. 1,2 Although the introduction of liquid-based cytology has not led to improvements in terms of relative sensitivity for the detection of cervical cancer precursors, 3 this technique has enabled the use of adjunctive tests that may help to reduce the rate of false-negative cytological results and add objectivity to the classical morphological evaluation.High-risk human papillomaviruses (HPV) are the causative agents of cervical cancer, and high-risk HPV testing has shown to improve the sensitivity of the Pap test to over 95%. 4,5 However, high-risk HPV tests have a lower specificity than...

There is growing interest in anal cancer screening strategies. However, cytological/molecular evaluation of anal samples is challenging. We aimed to determine the feasibility of detecting, in anal liquid-based cytologies, the expression of biomarkers involved in the cell cycle disturbance elicited by human papillomavirus (HPV). The accuracy of this approach in the identification of high-grade squamous intraepithelial lesions/anal intraepithelial neoplasia grade2–3 (HSIL/AIN2–3) was also evaluated. 215 anal cytologies from men having sex with men living with human immunodeficiency virus were evaluated. Patients showing concordant cytological and anoscopy-directed biopsy diagnosis were selected: 70 with negative cytology and HPV test, 70 with low-grade SIL (LSIL/AIN1) cytology and biopsy, and 75 with cytology and biopsy of HSIL/AIN2–3. CDKN2A/p16, MKI67 and TOP2A mRNA expression was analyzed. HPV detection was performed with Xpert HPV Assay (Cepheid, Sunnyvale, CA, USA). HSIL/AIN2–3 showed higher expression for the biomarkers than LSIL/AIN1 or negative samples. The specificity for HSIL/AIN2–3 detection for a sensitivity established at 70% was 44.7% (95%confidence interval [CI] 36.5–53.2) for TOP2A and MKI67 and 54.5% (95%CI 46.0–62.8%) for CDKN2A/p16. mRNA detection of cell biomarkers in anal liquid-based cytology is feasible. Further studies are warranted to confirm if strategies based on mRNA detection have any role in anal cancer screening.

33 Background: Cervical cancer screening programs in Low and Middle Income Countries (LMIC) need to be strengthened. One of the challenges is insufficient health care personnel to achieve optimal coverage. We evaluated the potential of human papillomavirus (HPV) testing using self-collected vaginal swabs to improve screening. Methods: As part of a larger NCI-supported study in Cape Town, South Africa, we recruited 261 HIV-uninfected and 237 HIV-infected women aged 30-60 years, at one primary health care site. All women were instructed to self-collect a vaginal swab on site immediately prior to a gynecologic exam, during which a cervical sample was collected. Both self- and clinician-collected samples were tested for high risk HPV types (16, 18, 45, 31, 33, 35, 52, 58, 51, 59, 39, 56, 66, 68) using Cepheid GeneXpert (HPV XpertTM). All women underwent at least one colposcopy with histological sampling. Classification of endpoint was based on expert pathology review. Results: The HPV prevalence using the cervical vs. self sample, respectively, was 14% vs. 25% among HIV-uninfected and 50% vs. 62% among HIV-infected women. Among women who were diagnosed with grade 2 or 3 cervical intraepithelial neoplasia (CIN) or cervical cancer, 94% were positive on HPV Xpert on the cervical and 88% on the vaginal swab, ignoring HIV status. However, specificity was poor for HPV tests done on self samples, 78% in HIV-uninfected and 52% in HIV-infected women. On a patient preference questionnaire, >90% of women stated they would be prepared to collect a sample at home and two-thirds expressed a preference to be examined by a clinician. Conclusion: Even in self-collected vaginal samples, HPV Xpert has excellent sensitivity for detecting cervical cancer precursor lesions. In LMIC settings where the ratio of health care workers to the population is low, HPV testing of self-collected samples could successfully triage women who require further evaluation and treatment. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST: Louise Kuhn No relationship to disclose Rakiya Saidu No relationship to disclose Cecilia Svanholm-Barrie No relationship to disclose Ana Tergas Consulting or Advisory Role: Helomics Rosalind Boa No relationship to disclose Jennifer Moodley No relationship to disclose Thomas C. Wright No relationship to disclose David Persing No relationship to disclose Scott Campbell No relationship to disclose Lynette Denny No relationship to disclose