Thomas C WrightJr

Triage strategies are needed for primary human papillomavirus (HPV)‐based cervical cancer screening to identify women requiring colposcopy/biopsy. We assessed the performance of p16/Ki‐67 dual‐stained (DS) immunocytochemistry to triage HPV‐positive women and compared it to cytology, with or without HPV16/18 genotyping. A prospective observational screening study enrolled 35 263 women aged 25 to 65 years at 32 U.S. sites. Cervical samples had HPV and cytology testing, with colposcopy/biopsy for women with positive tests. Women without cervical intraepithelial neoplasia Grade 2 or worse (≥CIN2) at baseline (n = 3876) were retested after 1 year. In all, 4927 HPV‐positive women with valid DS results were included in this analysis. DS sensitivity for ≥CIN2 and ≥CIN3 at baseline was 91.2% (95% confidence interval [CI]: 86.8%‐94.2%) and 91.9% (95% CI: 86.1%‐95.4%), respectively, in HPV16/18‐positive women and 83.0% (95% CI: 78.4%‐86.8%) and 86.0% (95% CI: 77.5%‐91.6%) in women with 12 “other” genotypes. Using DS alone to triage HPV‐positive women showed significantly higher sensitivity and specificity than HPV16/18 genotyping with cytology triage of 12 “other” genotypes, and substantially higher sensitivity but lower specificity than using cytology alone. The risk of ≥CIN2 was significantly lower in HPV‐positive, DS‐negative women (3.6%; 95% CI: 2.9%‐4.4%), compared to triage‐negative women using HPV16/18 genotyping with cytology for 12 “other” genotypes (7.4%; 95% CI: 6.4%‐8.5%; P < .0001) or cytology alone (7.5%; 95% CI: 6.7%‐8.4%; P < .0001). DS showed better risk stratification than cytology‐based strategies and provided high reassurance against pre‐cancers both at baseline and at 1‐year follow‐up, irrespective of the HPV genotype. DS allows for the safe triage of primary screening HPV‐positive women.

The Lower Anogenital Squamous Terminology (LAST) Project recommends the use of p16 immunohistochemistry as an adjunct to morphologic assessment of cervical biopsies according to a specific set of criteria. We analyzed the effect of adjunctive p16 according to LAST criteria in a US-based diagnostic utility study involving 70 surgical pathologists providing a total of 38,500 reads on cervical biopsies. Compared with the results obtained using hematoxylin and eosin-stained slides only, including p16-stained slides per LAST criteria increased sensitivity and specificity for diagnosing histologic high-grade squamous intraepithelial lesions across all cases by 8.1% (95% confidence interval [95% CI], 6.5-9.7; PPPPPP<0.0001). The study demonstrates a clinically and statistically significant increase in sensitivity and specificity for high-grade squamous intraepithelial lesion when p16 is used according to LAST criteria. Expanding the use of p16 into non-LAST cases would lead to a comparable improvement in sensitivity within this subgroup of biopsies, at the cost of a minimal, but statistically significant difference in specificity.

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.

South African women’s perspectives on self-sampling for cervical cancer screening: A mixed-methods study

To determine clinical utility of Onclarity human papillomavirus (HPV) assay for atypical squamous cells-undetermined significance (ASC-US) triage, and the value of HPV genotyping within ASC-US. Women (n = 33,858; 21 years or older) had HPV testing using Onclarity and Hybrid Capture 2 (HC2). ASC-US individuals (n = 1,960, 5.8%) were referred to colposcopy. Of ASC-US, 39.1% were HPV positive by Onclarity; HPV 16 was the most prevalent genotype (7.4%). Cervical intraepithelial neoplasia grade 2 (CIN 2) and CIN 3+ prevalences were 4.4% and 2.2%, respectively. Onclarity had sensitivity for CIN 2+ (85.7%) and CIN 3+ (91.4%), and specificities for CIN 2+ (64.1%) and CIN 3+ (62.0%), similar to HC2. Risks for CIN 3+ were 16.1%, 2.8%, 2.5%, and 2.7% with HPV 16, 18, 45, and 11 other genotypes, respectively. Onclarity is clinically validated for ASC-US triage. Through risk stratification, genotyping could help identify women at highest risk for CIN 3+.