Cervical cancer development is linked to the persistent infection by high-risk mucosal human papillomaviruses (HPVs) types. The E6 and E7 major oncoproteins from this dsDNA virus play a key role in the deregulation of the cell cycle, apoptosis, and adaptive immune surveillance. In this study, we show for the first time that HPV type 16 (HPV16), the most carcinogenic type among the high-risk subgroup, interferes with innate immunity by affecting the expression of TLRs. Infection of human primary keratinocytes with HPV16 E6 and E7 recombinant retroviruses inhibits TLR9 transcription and hence functional loss of TLR9-regulated pathways. Similar findings were achieved in HPV16-positive cancer-derived cell lines and primary cervical cancers, demonstrating that this event occurs also in an in vivo context. Interestingly, E6 and E7 from the low-risk HPV type 6 are unable to down-regulate the TLR9 promoter. In addition, E6 and E7 from the high-risk HPV type 18, which are known to persist less competently in the host than HPV16, have reduced efficiency compared with HPV16 in inhibiting TLR9 transcription. Furthermore, a CpG motif derived from the HPV16 E6 DNA sequence activated TLR9, indicating this virus is able to initiate innate responses via the receptor it later down-regulates. This study reveals a novel mechanism used by HPV16 to suppress the host immune response by deregulating the TLR9 transcript, providing evidence that abolishing innate responses may be a crucial step involved in the carcinogenic events mediated by HPVs.
New colposcopy terminology was prepared by the Nomenclature Committee of the International Federation of Cervical Pathology and Colposcopy after a critical review of previous terminologies, online discussions, and discussion with national colposcopy societies and individual colposcopists. This document has been expanded to include terminology of both the cervix and vagina. The popular terms "satisfactory colposcopy" and "unsatisfactory colposcopy" have been replaced. The colposcopic examination should be assessed for three variables: 1) adequate or inadequate, with the reason given; 2) squamocolumnar junction visibility; and 3) transformation zone type. Other additions were the localization of the lesion to either inside or outside the transformation zone and determinants of size as well as location of cervical lesions. Two new signs were included in the terminology-the "inner border sign" and "ridge sign." The following definitions have been added: congenital transformation zone, polyp (ectocervical or endocervical), stenosis, congenital anomaly, and posttreatment consequence. In addition, the terminology includes standardization of cervical excision treatment types and cervical excision specimen dimensions. The International Federation of Cervical Pathology and Colposcopy recommends that the 2011 terminology replace all others and be implemented for diagnosis, treatment, and research.
Three hundred patients were enrolled in a double-blind, randomized, controlled study designed to investigate the ability of supplemental perioperative oxygen to reduce wound infection. Participants were age 18 to 80 years, had no coexisting serious medical conditions, and were scheduled to undergo elective colorectal surgery at one of 14 participating hospitals in Spain. No patients undergoing minor or laparoscopic surgery were included. Anesthesia and antibiotic prophylaxis were standardized for the study. Patients were randomized by computer-generated codes to receive an oxygen/air mixture of 30% or 80% fraction of inspired oxygen (F10 2 ) intraoperatively and postoperatively for 6 hours. After 6 hours, oxygen was given only in amounts needed to maintain 92% saturation. Postoperative care was determined by the attending surgeon who was unaware of the patient's oxygen group.Wounds were inspected daily and surgical site infections (SSI) were diagnosed according to the definitions of the Centers for Disease Control and Prevention. Infections occurring during the first 14 days were considered for analysis.Nine patients did not meet inclusion criteria. Of the remaining 291 patients, 143 received 30% and 148 received 80% oxygen. The 2 groups were similar in clinical characteristics, including preoperative laboratory studies and risk of infection score. Surgical characteristics, including length of operative procedure, blood loss, and transfusion rate, were also similar between the 2 groups.Fifty-seven patients (19.3%) developed a wound infection. The incidence of wound infection was 35 of 143 (24%) in the 30% F10 2 group and 22 of 148 (14.9%) in the 80% F10 2 patients (P ϭ 0.04). The risk of SSI was 39% lower in the high oxygen group compared with those who received less oxygen (relative risk, 0.61; 95% confidence interval [CI], 0.38-0.98). Other measures of surgical outcome, including return of bowel function, ability to tolerate solid food, ambulation, suture removal, and duration of hospitalization, were not significantly different for the 2 treatment groups. When patients who developed wound infections were compared with those without infection, the group with SSI had a longer time to ambulation (mean, 4.9 vs 3.9 days; P ϭ 0.008), a longer time to staple removal (11.6 vs 10.1 days; P ϭ 0.007), and were in the hospital longer (15.1 vs 10.7 days; P ϭ 0.001).Two patients, both in the 30% oxygen group, died of sepsis during the study period. After multivariate analysis of possible confounding variables, the relative risk of wound infection in patients who received 80% oxygen was 0.46 (95% CI, 0.22-0.95; P ϭ 0.04) compared with those who received 30% oxygen. EDITORIAL COMMENT(In the United States these days, surgical wound infection occurs after less than 1% of abdominal or vaginal hysterectomies. This is a marked reduction in the last 20 years brought about largely because of prophylactic antibiotics. More than 25 prospective, randomized studies have shown the effectiveness of prophylactic antibiotics in reducing pos...
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