No Evidence for Synergy Between Human Papillomavirus Genotypes for the Risk of High-Grade Squamous Intraepithelial Lesions in a Large Population-Based Study

Human papillomavirus (HPV) infection is associated with the vast majority of cervical cancer cases as well as with other anogenital cancers. PepCan is an investigational HPV therapeutic vaccine for treating cervical high-grade squamous intraepithelial lesions. The present study was performed to test whether the cervical microbiome influences vaccine responses and to explore host factors as determinants of the cervical microbiome composition in women with biopsy-proven high-grade squamous intraepithelial lesions. In a recently completed Phase I clinical trial of PepCan, histological response rate of 45% (14 of 31 patients), a significant increase in circulating T-helper type 1 cells, and a significant decrease in HPV 16 viral load were reported. DNA, extracted from liquid cytology specimens collected before and after vaccinations, were amplified and then hybridized to a G4 PhyloChip assay to characterize the microbiome. We describe trends that certain bacterial taxa in the cervix may be enriched in non-responders in comparison to responders ( Padj = .052 for phylum Caldithrix and Padj = .059 for phylum Nitrospirae). There was no difference in bacterial diversity between the 2 groups. A permutational analysis of variance performed for various demographic and immune parameters showed significant clustering with microbiome beta diversity for race, HPV 16 status, peripheral T-helper type 1 cells, and HLA-B40 ( P = .001, .014, .037, and .024, respectively). Further analyses showed significant differences at the empirical Operational Taxonomic Unit level for race and HPV 16 status. As these results are from a small Phase I study, further studies are needed to examine the role of cervical microbiome in response to HPV therapeutic vaccines.

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The performance of human papillomavirus biomarkers in predicting anal high-grade squamous intraepithelial lesions in gay and bisexual men

AIDS ◽

10.1097/qad.0000000000001462 ◽

2017 ◽

Vol 31 (9) ◽

pp. 1303-1311 ◽

Cited By ~ 17

Author(s):

Fengyi Jin ◽

Jennifer M. Roberts ◽

Andrew E. Grulich ◽

Isobel M. Poynten ◽

Dorothy A. Machalek ◽

...

Keyword(s):

Human Papillomavirus ◽

Gay And Bisexual Men ◽

High Grade ◽

Bisexual Men ◽

Squamous Intraepithelial Lesions ◽

And Bisexual ◽

Intraepithelial Lesions

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DNA methylation in human papillomavirus-infected cervical cells is elevated in high-grade squamous intraepithelial lesions and cancer

Journal of Gynecologic Oncology ◽

10.3802/jgo.2016.27.e14 ◽

2016 ◽

Vol 27 (2) ◽

Cited By ~ 5

Author(s):

Mi-Kyung Kim ◽

In-Ho Lee ◽

Ki-Heon Lee ◽

Yoo Kyung Lee ◽

Kyeong A So ◽

...

Keyword(s):

Dna Methylation ◽

Human Papillomavirus ◽

High Grade ◽

Squamous Intraepithelial Lesions ◽

Cervical Cells ◽

Intraepithelial Lesions

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Infections with Multiple High-risk Human Papillomavirus (HPV) Types are Associated with More High-grade Squamous Intraepithelial Lesions (HSIL) on Follow-up Cervical Biopsy

Journal of the American Society of Cytopathology ◽

10.1016/j.jasc.2017.06.065 ◽

2017 ◽

Vol 6 (5) ◽

pp. S26-S27

Author(s):

Remegio Maglantay ◽

Brenda Sweeney ◽

Ivan Chebib ◽

David Wilbur

Keyword(s):

Human Papillomavirus ◽

High Risk ◽

High Grade ◽

Squamous Intraepithelial Lesions ◽

Cervical Biopsy ◽

Hpv Types ◽

Intraepithelial Lesions

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The value of p16INK4a immunostaining for high-grade squamous intraepithelial lesions in human papillomavirus–negative patients

10.21203/rs.3.rs-22799/v2 ◽

2020 ◽

Author(s):

Dai Zhang ◽

Jie Song ◽

Xiaosong Zhang ◽

Hui Bi

Keyword(s):

Human Papillomavirus ◽

Predictive Value ◽

Intraepithelial Neoplasia ◽

Pathological Diagnosis ◽

High Grade ◽

Squamous Intraepithelial Lesions ◽

P16 Ink4a ◽

Objective Detection ◽

High Risk Hpv ◽

Intraepithelial Lesions

Abstract Background : This study aims to evaluate the value of p16 INK4a immunostaining for high-grade squamous intraepithelial lesions in human papillomavirus–negative patients in Beijing, China. Methods: In this study, we evaluated the value of p16 INK4a immunostaining, as well as cytology and colposcopy, for predicting high-grade squamous intraepithelial lesions (HSIL) in human papillomavirus (HPV)-negative patients by comparing the methods with the haematoxylin and eosin (H&E) staining pathological diagnosis of HPV-negative patients. Results: Of 122 patients negative for the high-risk HPV (HR-HPV) subtype, 26 (21.3%) underwent colposcopically directed multiple punch cervical biopsy with a H&E pathological diagnosis of HSIL and above (HSIL+), 11 patients (9.0%) had cervical intraepithelial neoplasia (CIN)2, nine patients (7.4%) had CIN3, and six patients (4.9%) had infiltrating carcinoma. Cytology, colposcopy, and p16 INK4a immunostaining had 52.4%, 38.5%, and 92.3% sensitivity, respectively, and 76.2%, 94.8%, and 99% specificity, respectively. The positive predictive value of cytology, colposcopy, and p16 INK4a immunostaining was 31.4%, 66.7%, and 96%, respectively, and the negative predictive value was 88.5%, 85.1%, and 97.9%, respectively. Compared with H&E staining, the kappa of cytology, colposcopy, and p16 INK4a immunostaining was 0.327, 0.323, and 0.926, respectively. Conclusion: Positive p16 INK4a immunostaining is very strongly consistent with an H&E diagnosis of CIN2+, and it can be used as an objective detection index for HSIL+ diagnosis of HPV-negative patients with CIN2+.

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Coinfection of High-Risk Human Papillomavirus and Lower Genital Tract Pathogens in the Development of High-Grade Cervical Lesions

Canadian Journal of Infectious Diseases and Medical Microbiology ◽

10.1155/2020/7640758 ◽

2020 ◽

Vol 2020 ◽

pp. 1-8

Author(s):

Hui Zhong ◽

Yao Tong ◽

Haifeng Lin ◽

Xiaodan Mao ◽

Binhua Dong ◽

...

Keyword(s):

Human Papillomavirus ◽

High Risk ◽

Genital Tract ◽

Hpv Infection ◽

High Grade ◽

Infection Rates ◽

Squamous Intraepithelial Lesions ◽

Cervical Lesions ◽

Lower Genital Tract ◽

Intraepithelial Lesions

Purpose. This study investigated the infection status and relationship between other common lower genital tract infectious pathogens and high-risk human papillomavirus (HR-HPV) in the high-grade cervical lesions. Methods. Overall, 882 patients were enrolled in this retrospective study, of which 339 patients (≥HSIL group) were confirmed with high-grade squamous intraepithelial lesions (HSIL) or cervical squamous cell carcinoma (SCC), while 543 patients (≤LSIL group) were diagnosed with low-grade squamous intraepithelial lesions (LSIL) or normal cervical pathology diagnosis. Cervical swab specimens were tested for HPV, pathogenic bacteria (PB), U. urealyticum (UU), M. hominis (MH), and C. trachomatis (CT) in both groups. Results. The infection rates of HR-HPV, PB, UU (at high density), and CT were higher in the ≥HSIL group than in the ≤LSIL group (P<0.001); however, higher infection rates with MH were not observed (P>0.05). PB, UU, and CT were associated with HR-HPV infection (P<0.001). The PB and UU infection rates in the ≥HSIL group were significantly different from those in the ≤LSIL group, regardless of whether there was an HR-HPV infection at the same time (P<0.05). However, this was not the case for the CT (P>0.05). Furthermore, 259 pathogenic bacterial strains were detected in 882 cases. The difference in the distribution of pathogenic bacterial flora in the different grades of cervical lesions had no statistical significance, which was prioritized over Escherichia coli (P>0.05). Conclusion. PB, UU, and CT infection is associated with susceptibility to HR-HPV, HR-HPV coinfection with these pathogens might increase the risk of high-grade cervical lesions, and PB and UU might be independent risk factors for cervical lesions.

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