BackgroundPapanicolaou (Pap) triage, with high specificity, has been recommended for primary Human papillomavirus (HPV) testing but is flawed by poor sensitivity and cytologist dependence. We evaluated the potential role of microRNA (miRNA) detection in cervical exfoliated cells in HPV-positive women from a clinic-based population.MethodsPrimary HPV testing as well as Pap test were performed on all eligible women. Six miRNAs (miR-424/miR-375/miR-34a/miR-218/miR-92a/miR-93) were detected by RT-qPCR in cervical exfoliated cells. All HPV-positive women underwent colposcopy and further biopsy if indicated. Mann–Whitney U test, the receiver operating characteristic curve, logistic regression, and Pearson’s Chi-square were used to assess data. All tests of statistical significance were two-sided.ResultsA total of 1021 eligible HPV-positive women were enrolled. The expression of miR-424/miR-375/miR-34a/miR-218 in high-grade cervical intraepithelial neoplasia (CIN) and abnormal cytology was statistically significantly lower than that in low-grade CIN and normal cytology, respectively (all P < .05). Compared with the Pap test, both miR-424 and miR-375 detection achieved higher sensitivity (76.0% and 74.9% vs 63.8%, P < .05), higher negative predictive value (NPV) (85.7% and 85.4% vs 79.3%, P < .05), and comparable specificity while identifying CIN2 or worse (CIN2+). Similar results were achieved while identifying CIN3+. Multi-marker panels based on miR-424, miR-375, and miR-218 further improved the performance over any single miRNA test or Pap test.ConclusionSingle miR-424 or miR-375 detection and miR-424/miR-375/miR-218–based multimarker panels in cervical exfoliated cells show superior performance over Pap triage for high-grade CIN identification in a clinic-based population. Detection of miRNA may provide a new triage option for HPV-positive women.

It has been shown that HPV16 E7, but not other genotypes, can bind to scaffold protein CUL2 during inducing cervical carcinogenesis, but the expression level, associated regulating mechanism, and potential carcinogenicity of CUL2 itself is still unknown as yet. Here, we demonstrated that CUL2 was specifically overexpressed in HPV16 positive cervical cancer cells and tissues, and CUL2 expression was significantly increased along with the cervical lesion progression and positively correlated with HPV16 E7. CUL2 knockdown slowed the growth of xenograft tumors in mouse models. Importantly, CUL2 specifically bound to HPV16 E7, but not HPV18 E7. Moreover, CUL2 acted as a direct target of miR-424, and reversely suppressed miR-424; E2F transcription factor 1 (E2F1) suppressed miR-424 expression; CUL2 bound to E2F1 and promoted E2F1 expression. Our results indicate the existence of a regulatory loop among CUL2, E2F1, and miR-424 in HPV16 positive cervical cancer cells. Our results suggest that E7 recruited CUL2, driven by CUL2/E2F1/miR-424 regulatory loop, is overexpressed and accelerates HPV16-induced cervical carcinogenesis. Our findings may serve as one of the explanations for a clinical phenomenon that HPV16 possesses the strongest cervical carcinogenicity among high-risk HPV genotypes.

Cytology triage has been generally recommended for human papillomavirus (HPV)-positive women, but is highly dependent on well-trained cytologists. The present study was designed to explore whether HPV E6/E7 mRNA detection in cervical exfoliated cells can be a potential triage for HPV-positive women from a clinic-based population. Both the primary HPV testing and Papanicolaou (Pap) test were performed on all eligible HPV-positive women. HPV E6/E7 mRNA was detected by QuantiVirus HPV E6/E7 mRNA assay in cervical exfoliated cells. All HPV-positive women underwent colposcopy and further biopsy if indicated. The data were assessed by Pearson's Chi-squared test and the receiver operating characteristic curve. A total of 404 eligible HPV-positive women were enrolled. Positive rate of E6/E7 mRNA in high-grade squamous intraepithelial lesion (HSIL) cases was higher than that in low-grade squamous intraepithelial lesion (LSIL) or normal cases. There was no statistical difference found between mRNA and cytological testing with sensitivity (89.52% vs. 86.67%, P=0.671), specificity (48.96% vs. 48.96%, P=1.000), positive predictive value (39.00% vs. 38.24%, P=1.000), and negative predictive value (92.76% vs. 90.97%, P=0.678) for detecting ≥HSIL. HPV E6/E7 mRNA detection in cervical exfoliated cells shows the same performance as Pap triage for HSIL identification for HPV-positive women. Detection of HPV E6/E7 mRNA may be used as a new triage option for HPV-positive women.

Rationale:The incidence of spontaneous perforations in pyometra occurs rarely, only 0.01% to 0.5% in gynecological patients, with high mortality and morbidity. The clinical manifestation of perforated uterine pus is similar to that of gastrointestinal perforation, but the gynecological symptoms are not so obvious, which makes preoperative diagnosis difficult. Here, we report a rare case of peritonitis with laparotomy of pyometra.Patient concerns:An acute abdominal pain and purulent vaginal discharge developed in a 72-year-old woman who underwent an emergency laparotomy because of signs of diffuse peritonitis and in a state of shock.Diagnoses:We made a diagnosis of spontaneous perforation of pyometra.Interventions:At laparotomy, about 1000 mL of pus with the source of uterine was found in the abdominal cavity, while gastrointestinal tract was intact and a crevasse with a diameter of 1.5 cm on posterior uterine wall was obvious. A total abdominal hysterectomy and a bilateral salphingo oophorectomy were performed.Outcomes:The patient got discharged on 34th postoperative hospitalization day with only 1 complication of wound healing. Histopathological study revealed uterine purulent inflammation, with no evidence of malignancy.Lessons:Ultrasonography is the first and most sensitive examination for the evaluation of pyometra, but has limited role in the diagnosis of perforated pyometra. Additional diagnostic radiographic evaluation use for acute abdomen is total abdomen computed tomography scan and magnetic resonance imaging techniques of female pelvis.

p21 Codon 31 with AGA (Arg) allele is a genetic risk factor of cervical SCC, and the increased risk is probably not caused by increasing host susceptibility to HR-HPV infection.