Purpose To determine whether HPV DNA can be detected in the plasma of patients with HPV(+) oropharyngeal carcinoma (OP) and to monitor its temporal change during radiotherapy (RT). Methods and Materials We used PCR to detect HPV DNA in the culture media of HPV(+) SCC90, VU147T and the plasma of SCC90 and HeLa tumor bearing mice, non-tumor controls and those bearing HPV(-) tumors. We used real time quantitative PCR (qPCR) to quantify plasma HPV DNA in 40 HPV(+) OP, 24 HPV(-) head and neck cancer (HNC) patients and 10 non-cancer volunteers. Tumor HPV status was confirmed by p16INK4a staining and HPV16/18 PCR or HPV ISH. 14 patients had serial plasma samples for HPV DNA quantification during RT. Results HPV DNA was detectable in the plasma samples of SCC90- and HeLa-bearing mice but not in controls. It was detected in 65% of pretreatment plasma samples from HPV(+) OP patients using E6/7 qPCR. None of the HPV(-) HNC or non-cancer controls had detectable HPV DNA. Pretreatment plasma HPV DNA copy number correlated significantly with nodal metabolic tumor volume (assessed on FDG-PET). Serial measurements in 14 patients showed rapid decline in HPV DNA that became undetectable at RT completion. In 3 patients, HPV DNA rose to discernable level at the time of metastasis. Conclusions Xenograft studies indicated that plasma HPV DNA is released from HPV(+) tumors. Circulating HPV DNA is detectable in most HPV(+) OP patients. Plasma HPV DNA may be a valuable tool for identifying relapse.
Although the incidence of human papillomavirus (HPV)-associated anal neoplasia is increasing, interobserver and intraobserver reproducibility in the grading of biopsy specimens from this area remains unacceptably low. Attempts to produce a more reproducible grading scheme have led to the use of biomarkers for the detection of high-risk HPV (HR-HPV). We evaluated the performance of standard morphology and biomarkers p16, ProEx C, and Ki-67 in a set of 75 lesions [17 nondysplastic lesions, 23 low-grade squamous intraepithelial lesions (LSIL)/condyloma, 20 high-grade squamous intraepithelial lesions (HSIL), 15 invasive squamous cell carcinomas] from the anal and perianal region in 65 patients and correlated these findings with HPV subtype on the basis of a type-specific multiplex real-time polymerase chain reaction assay designed to detect HR-HPV. A subset of cases with amplifiable HPV DNA was also sequenced. HSIL was typically flat (15/20), and only a minority (4/20) had koilocytes. In contrast, only 1 LSIL was flat (1/23), and the remainder were exophytic. The majority of LSIL had areas of koilocytic change (20/23). HR-HPV DNA was detected in the majority (89%) of invasive carcinomas and HSIL biopsies, 86% and 97% of which were accurately labeled by strong and diffuse block-positive p16 and ProEx C, respectively. LSIL cases, however, only infrequently harbored HR-HPV (13%); most harbored low-risk HPV (LR-HPV) types 6 and 11. Within the LSIL group, p16 outperformed ProEx C, resulting in fewer false-positive cases (5% vs. 75%). Ki-67 was also increased in HR-HPV-positive lesions, although biopsies with increased inflammation and reactive changes also showed higher Ki-67 indices. These data suggest that strong and diffuse block-positive nuclear and cytoplasmic labeling with p16 is a highly specific biomarker for the presence of HR-HPV in anal biopsies and that this finding correlates with high-grade lesions.
We sought to address the significance of isolated follicles that exhibit atypical morphologic features that may be mistaken for lymphoma in a background of reactive lymphoid tissue. Seven cases that demonstrated centroblast-predominant isolated follicles and absent BCL2 staining in otherwise-normal lymph nodes were studied. Four of seven cases showed clonal B-cell proliferations amid a polyclonal B cell background; all cases lacked the IGH-BCL2 translocation and BCL2 protein expression. Although three patients had invasive breast carcinoma at other sites, none were associated with systemic lymphoma up to 44 months after diagnosis. The immunoarchitectural features of these highly unusual cases raise the question of whether a predominance of centroblasts and/or absence of BCL2 expression could represent a precursor lesion or atypical reactive phenomenon. Differentiating such cases from follicular lymphoma or another mimic is critical, lest patients with indolent proliferations be exposed to unnecessarily aggressive treatment.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.