The Role of High-resolution Anoscopy and Random Biopsies: The Role of Infrared Coagulation vs Active Monitoring in the Treatment of High-grade Squamous Intraepithelial Lesions

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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The role of smoking and alcohol intake in the development of high-grade squamous intraepithelial lesions among high-risk HPV-positive women

Acta Obstetricia Et Gynecologica Scandinavica ◽

10.1080/00016340600677027 ◽

2006 ◽

Vol 85 (9) ◽

pp. 1114-1119 ◽

Cited By ~ 21

Author(s):

Janne Tolstrup ◽

Christian Munk ◽

Birthe Lykke Thomsen ◽

Edith Svare ◽

Adriaan J.C. van den Brule ◽

...

Keyword(s):

High Risk ◽

Alcohol Intake ◽

High Grade ◽

Squamous Intraepithelial Lesions ◽

High Risk Hpv ◽

Intraepithelial Lesions

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The role of miR-409-3p in regulation of HPV16/18-E6 mRNA in human cervical high-grade squamous intraepithelial lesions

Antiviral Research ◽

10.1016/j.antiviral.2019.01.019 ◽

2019 ◽

Vol 163 ◽

pp. 185-192 ◽

Cited By ~ 2

Author(s):

Lucia Sommerova ◽

Milan Anton ◽

Pavla Bouchalova ◽

Hedvika Jasickova ◽

Vladimir Rak ◽

...

Keyword(s):

High Grade ◽

Squamous Intraepithelial Lesions ◽

Intraepithelial Lesions

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High-Resolution Anoscopy Targeted Surgical Destruction of Anal High-Grade Squamous Intraepithelial Lesions: A Ten-Year Experience

Diseases of the Colon & Rectum ◽

10.1007/s10350-008-9233-4 ◽

2008 ◽

Vol 51 (6) ◽

pp. 829-837 ◽

Cited By ~ 118

Author(s):

Carlos E. Pineda ◽

J. Michael Berry ◽

Naomi Jay ◽

Joel M. Palefsky ◽

Mark L. Welton

Keyword(s):

High Resolution ◽

High Grade ◽

Squamous Intraepithelial Lesions ◽

Intraepithelial Lesions

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Prevalence of and Risk Factors for Anal High-grade Squamous Intraepithelial Lesions in Women Living with Human Immunodeficiency Virus

Clinical Infectious Diseases ◽

10.1093/cid/ciz408 ◽

2019 ◽

Vol 70 (8) ◽

pp. 1701-1707 ◽

Cited By ~ 4

Author(s):

Elizabeth A Stier ◽

Shelly Y Lensing ◽

Teresa M Darragh ◽

Ashish A Deshmukh ◽

Mark H Einstein ◽

...

Keyword(s):

United States ◽

Risk Factors ◽

Human Immunodeficiency Virus ◽

High Resolution ◽

The United States ◽

High Grade ◽

Squamous Intraepithelial Lesions ◽

Immunodeficiency Virus ◽

History Of ◽

Intraepithelial Lesions

Abstract Background Women living with human immunodeficiency virus (WLHIV) have disproportionately high rates of squamous cell carcinoma of the anus compared with the general population of women. Anal high-grade squamous intraepithelial lesions (HSILs) precede anal cancer, and accurate studies of HSIL prevalence among WLHIV in the United States are lacking. Methods The AIDS Malignancy Consortium 084 study was a multicenter national trial to evaluate the prevalence of and risk factors for anal HSIL in a US cohort. Eligible participants were WLHIV aged ≥18 years with no history of anal HSIL. Study participants had an examination including collection of cervical/vaginal and anal specimens, followed by high-resolution anoscopy with biopsy. Results We enrolled 256 women with evaluable anal pathology. The mean age was 49.4 years, 64% women were non-Hispanic black, 67% were former or current smokers, and 56% reported ever having anal sex with a man. The median CD4 T-cell count was 664 cells/μL. The prevalence of anal histologic HSIL (hHSIL) was 27% (95% confidence interval [CI], 22%–33%). There was a strong concordance (240/254) between local and consensus pathologists for hHSIL vs less than hHSIL (κ = 0.86 [95% CI, .79–.93]). Current CD4 count of ≤200 cells/μL was the strongest predictor of consensus anal hHSIL diagnosis (adjusted odds ratio [aOR], 10.34 [95% CI, 3.47–30.87]). History of anoreceptive intercourse was also associated with hHSIL (aOR, 2.44 [95% CI, 1.22–4.76]). Conclusions The prevalence of anal hHSIL in WLHIV in the United States was 27% in this study where all participants received high-resolution anoscopy and biopsy.

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

Sexual Health ◽

10.1071/shv10n6ab32 ◽

2013 ◽

Vol 10 (6) ◽

pp. 585

Author(s):

Joel Palefsky ◽

Maria Da Costa ◽

Teresa M. Darragh ◽

Naomi Jay ◽

J. Michael Berry

Keyword(s):

Anal Cancer ◽

High Grade ◽

Squamous Intraepithelial Lesions ◽

Hpv 16 ◽

Hpv Dna ◽

Formalin Fixed Paraffin ◽

Formalin Fixed Paraffin Embedded ◽

Location Methods ◽

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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