32. HPV type and strain variant concordance between anal cancers and their preceding high-grade squamous intraepithelial lesions

Background Anal high-grade squamous intraepithelial lesions (HSIL) are frequently found overlying anal cancer on histology, and anal cancer has been observed to develop in the same location as previously diagnosed anal HSIL. These observations support the role of HSIL as the direct precursor lesion to anal cancer. To further investigate a direct pathogenetic relationship between anal HSIL and cancer, we typed and sequenced HPV DNA in anal HSIL and the cancers that subsequently developed in the same location. Methods: Tissues samples were analysed from 15 HIV-infected men followed at UCSF in whom anal cancer developed at a previously biopsied site of HSIL. Formalin-fixed paraffin-embedded pairs of HSIL and cancer were typed for HPV DNA using L1 PCR. HPV 16-positive samples underwent E6-based strain variant analysis. Results: Nine matched pairs for which DNA from both HSIL and cancer were available were analysed. Eight pairs (89%) contained HPV 16 DNA. One (11%) contained both HPV 18 and 51 in both samples. Of the eight HPV 16-positive pairs, each pair contained the same HPV 16 strain variant. Four contained the Eur-350T variant alone, and one contained Eur-350T in both the HSIL and cancer, with an additional 426T variant in the cancer. One pair contained both Eur-350T and 457C in both the HSIL and the cancer. Two pairs contained the Eur-350G variant alone. Conclusions: Concordance of both the HPV type and strain variant in anal cancers and their site-matched preceding HSIL further supports the role of anal HSIL as an anal cancer precursor.

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Human papillomaviruses 16 and 58 are distributed widely among women living in Shanghai, China, with high-grade, squamous intraepithelial lesions

Epidemiology and Infection ◽

10.1017/s0950268818003011 ◽

2018 ◽

Vol 147 ◽

Cited By ~ 2

Author(s):

J. Xu ◽

Z. Xia ◽

L. Wang ◽

B. Yang ◽

Y. Zhu ◽

...

Keyword(s):

Human Papillomaviruses ◽

Low Grade ◽

High Grade ◽

Squamous Intraepithelial Lesions ◽

Hpv 16 ◽

Hpv Dna ◽

Control And Prevention ◽

Intraepithelial Lesion ◽

Hpv Dna Tests ◽

Intraepithelial Lesions

AbstractThe distribution of human papillomaviruses (HPVs) must be understood for the control and prevention of cervical cancer. Community-based Papanicolaou and HPV DNA tests were performed on 41 578 women. The prevalences of HPV genotypes 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68 were assessed. In total, 10% women were infected/co-infected by these HPVs. The infection rate increased from 7.1% in women aged ⩽30 years to 10.4% in those aged 50–60 years, and then decreased slightly to 9.9% in those aged >60 years. The HPV 16 and 58 positivity rates were significantly higher among women with high-grade squamous intraepithelial lesions (HSILs) than among those with cervicitis/negativity for intraepithelial lesion or malignancy (NILM) or low-grade SILs (LSILs). The HPV 18, 52 and 68 infection rates were significantly lower in women with HSILs than in those with NILM or LSILs. The proportion of women infected by multiple HPV strains was higher among those with HSILs. The proportions of the five most common genotypes, HPV 16, 18, 33, 52 and 58, increased with the number of co-infecting strains. HPV 16 and 58 were the high-risk HPVs in the Shanghai community and should be the focus in HPV screening and vaccination.

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Prognostic markers of high-grade squamous intraepithelial lesions: the role of p16INK4aand high-risk human papillomavirus

Acta Obstetricia Et Gynecologica Scandinavica ◽

10.1080/00016340601089727 ◽

2007 ◽

Vol 86 (1) ◽

pp. 94-98 ◽

Cited By ~ 19

Author(s):

José Eleutério Jr ◽

Paulo César Giraldo ◽

Ana Katherine Gonçalves ◽

Diane Isabelle Magno Cavalcante ◽

Francisco Valdeci de Almeida Ferreira ◽

...

Keyword(s):

Human Papillomavirus ◽

High Risk ◽

Prognostic Markers ◽

High Grade ◽

Squamous Intraepithelial Lesions ◽

Intraepithelial Lesions

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Relevance of the Pap Test: A Report of HPV-DNA Test-Negative High-Grade Squamous Intraepithelial Lesions of the Female Lower Genital Tract

Acta Cytologica ◽

10.1159/000448470 ◽

2016 ◽

Vol 60 (5) ◽

pp. 445-450 ◽

Cited By ~ 3

Author(s):

Yiang Hui ◽

Katrine Hansen ◽

Jayasimha Murthy ◽

Danielle Chau ◽

C. James Sung ◽

...

Keyword(s):

High Risk ◽

Pap Test ◽

Human Papillomaviruses ◽

High Grade ◽

Squamous Intraepithelial Lesions ◽

Cytologic Examination ◽

Dna Test ◽

Hpv Dna ◽

Intraepithelial Lesions ◽

Hpv Dna Test

Objective: A vast majority of cervicovaginal intraepithelial lesions are caused by high-risk human papillomaviruses (HPVs). The Pap test has been the sole method used for the screening of cervicovaginal squamous intraepithelial lesions (SIL). Recently, the FDA approved an HPV-DNA assay as a method of primary screening. We report on a series of FDA-approved HPV-DNA test-negative SIL with HPV genotyping, using an alternative method on the corresponding surgical biopsy specimens. Study Design: A retrospective review identified cytology-positive HPV-negative cases over a 15-month period at a tertiary care gynecologic oncology institution. Corresponding biopsies were reviewed and genotyped for high-risk HPVs. Results: Of the 18,200 total cases, 17 patients meeting the study criteria were selected with 27 surgical specimens corresponding to their cytologic diagnoses. Four patients with high-grade lesions were identified, 3 of whom (75%) were positive for HPV. One of these 4 patients (25%) showed high-grade SIL on biopsies from 4 separate sites in the cervix and vagina. Multiviral HPV infections were frequent. Conclusions: We discuss the relevance of cotesting for screening cervical SILs and emphasize that false-negative results are possible with the FDA-approved HPV screening assay, also in patients with high-grade SIL. These cases may be detectable by cytologic examination and this suggests that the Pap test remains an important diagnostic tool.

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Incorporation of Cervista Human Papillomavirus 16/18 Assay Into Algorithms for Classifying Human Papillomavirus Status in Formalin-Fixed, Paraffin-Embedded Head and Neck Squamous Carcinoma Specimens

Archives of Pathology & Laboratory Medicine ◽

10.5858/arpa.2017-0469-oa ◽

2018 ◽

Vol 143 (3) ◽

pp. 356-361

Author(s):

Ming Guo ◽

Abha Khanna ◽

Jianping Wang ◽

Michelle D. Williams ◽

Neda Kalhor ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Human Papillomavirus ◽

Ffpe Tissue ◽

Hpv 16 ◽

Hpv Dna ◽

Formalin Fixed Paraffin ◽

Hpv Status ◽

Formalin Fixed Paraffin Embedded ◽

Hpv Assays ◽

Formalin Fixed

Context.— Human papillomavirus (HPV) DNA in situ hybridization (ISH) assay and p16 immunohistochemistry (IHC) are used to determine high-risk HPV status in formalin-fixed, paraffin-embedded (FFPE) tissues in oropharyngeal squamous cell carcinoma (SCC). Although high sensitivity and specificity for HPV can be obtained by combined p16 IHC and HPV DNA ISH, the occasional discrepancy between these assays has prompted evaluation of Cervista HPV assays in FFPE tissue from patients with oropharyngeal SCC. Objective.— To compare the efficacy of Cervista HPV 16/18 and Cervista HPV HR assay to that of HPV DNA ISH assay and p16 IHC in FFPE tissue in head and neck squamous cell carcinoma of oropharyngeal origin. Design.— Archived FFPE tissue from 84 patients with SCC of oropharyngeal origin and available HPV DNA ISH and p16 IHC test results were tested with the Cervista HPV 16/18 assay and further verified by polymerase chain reaction (PCR)–based HPV16/18 genotyping tests in cases with discrepancy. Results.— Of the 84 specimens, 75% (63 of 84) were positive and 16% (13 of 84) had discrepant or equivocal findings by p16 IHC and HPV DNA ISH testing. Use of Cervista HPV assays, either to clarify discrepant/equivocal findings or as confirmation after initial p16 IHC/HPV DNA ISH tests, identified 81% (68 of 84) of HPV-positive cases without equivocal HPV results. Five of 13 cases with discrepancy or equivocal HPV DNA ISH results tested positive for HPV16 or HPV18 by Cervista HPV 16/18 assay, which was further confirmed by PCR-based HPV 16/18 genotyping. Conclusions.— The Cervista HPV assays are a reasonable alternative to HPV DNA ISH in determining HPV status in FFPE tissue specimens from patients with oropharyngeal SCC.

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Squamous cell carcinoma antigen combined with HPV-16 infection in predicting high-grade squamous intraepithelial lesions of the cervix

Journal of Obstetrics and Gynaecology ◽

10.1080/01443615.2021.1948511 ◽

2021 ◽

pp. 1-5

Author(s):

Guanglei Zhong ◽

Yuhan Wang ◽

Shixian Yao ◽

Xingyu Fang ◽

Rongchun Lin ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

High Grade ◽

Squamous Cell Carcinoma Antigen ◽

Squamous Intraepithelial Lesions ◽

Hpv 16 ◽

Intraepithelial Lesions

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Cervical Microbiome and Response to a Human Papillomavirus Therapeutic Vaccine for Treating High-Grade Cervical Squamous Intraepithelial Lesion

Integrative Cancer Therapies ◽

10.1177/1534735419893063 ◽

2019 ◽

Vol 18 ◽

pp. 153473541989306 ◽

Cited By ~ 1

Author(s):

Rahul Ravilla ◽

Hannah N. Coleman ◽

Cheryl-Emiliane Chow ◽

Luisa Chan ◽

Barbara J. Fuhrman ◽

...

Keyword(s):

Human Papillomavirus ◽

Phase I ◽

Therapeutic Vaccine ◽

High Grade ◽

T Helper ◽

Squamous Intraepithelial Lesions ◽

Hpv 16 ◽

Intraepithelial Lesions ◽

Helper Type

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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Relationship between the Cervical Microbiome, HIV Status, and Precancerous Lesions

mBio ◽

10.1128/mbio.02785-18 ◽

2019 ◽

Vol 10 (1) ◽

Cited By ~ 18

Author(s):

Cameron Klein ◽

Daniela Gonzalez ◽

Kandali Samwel ◽

Crispin Kahesa ◽

Julius Mwaiselage ◽

...

Keyword(s):

Hiv Positive ◽

High Grade ◽

Squamous Intraepithelial Lesions ◽

Cervical Lesions ◽

Cervical Cancers ◽

Bacterial Microbiome ◽

Bacterial Richness ◽

Intraepithelial Lesions ◽

Hiv Negative

ABSTRACT Nearly all cervical cancers are causally associated with human papillomavirus (HPV). The burden of HPV-associated dysplasias in sub-Saharan Africa is influenced by HIV. To investigate the role of the bacterial microbiome in cervical dysplasia, cytobrush samples were collected directly from cervical lesions of 144 Tanzanian women. The V4 hypervariable region of the 16S rRNA gene was amplified and deep sequenced. Alpha diversity metrics (Chao1, PD whole tree, and operational taxonomic unit [OTU] estimates) displayed significantly higher bacterial richness in HIV-positive patients (P = 0.01) than in HIV-negative patients. In HIV-positive patients, there was higher bacterial richness in patients with high-grade squamous intraepithelial lesions (HSIL) (P = 0.13) than those without lesions. The most abundant OTUs associated with high-grade squamous intraepithelial lesions were Mycoplasmatales, Pseudomonadales, and Staphylococcus. We suggest that a chronic mycoplasma infection of the cervix may contribute to HPV-dependent dysplasia by sustained inflammatory signals. IMPORTANCE HPV is known to be the causal agent in the majority of cervical cancers. However, the role of the cervical bacterial microbiome in cervical cancer is not clear. To investigate that possibility, we collected cervical cytobrush samples from 144 Tanzanian women and performed deep sequencing of bacterial 16S rRNA genes. We found that HIV-positive patients had greater bacterial richness (P = 0.01) than HIV-negative patients. We also observed that women with high-grade squamous intraepithelial lesions (HSIL) had greater cervical bacterial diversity than women with cytologically normal cervices. Data from our precise sampling of cervical lesions leads us to propose that Mycoplasma contributes to a cervical microbiome status that promotes HPV-related cervical lesions. These results suggest a greater influence of the bacterial microbiota on the outcome of HPV infection than previously thought.

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8. Human papillomavirus mRNA testing for the detection of anal high-grade squamous intraepithelial lesions in HIV-positive men who have sex with men

Sexual Health ◽

10.1071/shv10n6ab8 ◽

2013 ◽

Vol 10 (6) ◽

pp. 573

Author(s):

Elena Sendagorta Cudós ◽

Maria P. Romero Gomez ◽

Beatriz Hernandez Novoa ◽

Ander Mayor ◽

Jose I. Bernardino De La Serna ◽

...

Keyword(s):

Predictive Value ◽

Screening Program ◽

University Hospital ◽

High Grade ◽

Squamous Intraepithelial Lesions ◽

Cross Sectional ◽

Hpv Dna ◽

Hpv E6 ◽

Anal Cytology ◽

Intraepithelial Lesions

Background Currently, screening for anal high-grade squamous intraepithelial lesions (HSIL) relies on anal cytology and high-resolution anoscopy (HRA). Since this approach has limited sensitivity and specificity for detecting anal HSIL, there is increasing interest in the role of biomarkers for predicting anal HSIL. The aim of this study is to evaluate the diagnostic accuracy of HPV E6/E7-mRNA expression for the detection of anal HSIL in MSM HIV-infected patients, in comparison to DNA-HR-HPV and anal cytology. Methods: This cross-sectional screening study included 101 MSM followed at the HIV-unit of La Paz University Hospital. Intra-anal swabs from patients participating in a screening program including cytology, HRA and histology were analysed. HR-HPV-DNA detection was performed by means of the CLART HPV2 assay (GENOMICA SAU.). E6/E7-mRNA detection of HR-HPV types 16, 18, 31, 33 and 45 was performed using the NucliSENS-EasyQ assay (BioMérieux, Marcy l’Etoile, France). Results: HR-HPV DNA and HPV E6/E7 mRNA were detected in 82% and 57% of the anal smears, respectively. Anal cytology screening was abnormal in 70.3%. For the detection of HSIL sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 71.7%, 55.6%, 57.9%, and 69.8% for E6/E7-mRNA testing, respectively, compared with 97.9%, 31.5%, 55.4% and 94.4%, respectively, for HR-HPV DNA testing and 83%, 40.7%, 54.9%, 73.3%, respectively, for cytology testing. Conclusions: In comparison with the other tests, the NucliSENS EasyQ HPV assay yielded a lower clinical sensitivity but a higher clinical specificity and PPV for the detection of anal HSIL in MSM HIV-infected patients.

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