II.

Background HPV-based screen and treat is the recommended approach for cervical cancer screening in low-resource settings, but quite low specificity of human papillomavirus (HPV) testing, particularly in women living with HIV, leads to overtreatment. We evaluated whether HPV type restriction and more stringent cutoffs on Xpert HPV optimise performance characteristics of this assay for screen and treat. MethodsWe recruited HIV-negative and HIV-positive women aged 30-65 years from a primary care facility and a referral colposcopy clinic in Cape Town, South Africa. Women included had no history of any anogenital cancer or treatment for cervical dysplasia, had no hysterectomy, and were not pregnancy at the time of recruitment. All women had cervical samples collected for Xpert HPV (an assay that detects high-risk HPV types in five channels: HPV type 16; HPV types 18 or 45, or both; HPV types 31, 33, 35, 52, or 58, or more than one of these types; HPV types 51 or 59, or both; and HPV types 39, 56, 66, or 68, or more than one of these types) and underwent colposcopy and histological sampling with consensus pathology review. Logistic regression and receiver operating characteristic curves were used to evaluate improvements in specificity attained by modifying cycle threshold cutoffs to define screen-positive results. Results Werecruited 1121 women aged 30-65 years, 586 of whom were HIV-negative and 535 HIV-positive. Sensitivity of detecting cervical intraepithelial neoplasia grade 2 or greater in HIV-negative women using manufacturer-defined cycle threshold cutoffs for all channels was 88•7% (95% CI 83•1-94•3), and specificity was 86•9% (83•4-90•4). Sensitivity was 93•6% (90•0-97•3) and specificity 59•9% (54•1-65•7) in HIV-positive women. Cycle threshold values from channels detecting HPV type 16, HPV types 18 or 45 (or both), and HPV types 31, 33, 35, 52, or 58 (or more than one of these types) were informative to predict cervical intraepithelial neoplasia grade 2 or greater. Shifting cycle threshold cutoffs on these three channels allowing sensitivity to decline to 75-85%, led to specificities of 91•3-95•3% in HIV-negative women and 77•0-85•8% in HIV-positive women.Interpretation More stringent cycle threshold cutoffs on selected channels in Xpert HPV improve specificity with only modest losses in sensitivity, making this assay an optimal choice for HPV-based screen and treat in settings with a high prevalence of HIV. These modifications can be made from standard output with no need for new engineering. Decision making about performance characteristics of HPV testing can be shifted to programme implementers and cutoffs selected according to resource availability and community preferences.

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.