P33 Up-regulation of FOXP3 T regulatory lymphocytes in patients with high-grade squamous intraepithelial lesions correlated with HPV infection

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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Association of Bacterial Vaginosis and Human Papilloma Virus Infection With Cervical Squamous Intraepithelial Lesions

American Journal of Clinical Pathology ◽

10.1093/ajcp/aqz021 ◽

2019 ◽

Vol 152 (2) ◽

pp. 185-189 ◽

Cited By ~ 2

Author(s):

Wissam Dahoud ◽

Claire W Michael ◽

Hamza Gokozan ◽

Amelia K Nakanishi ◽

Aparna Harbhajanka

Keyword(s):

Bacterial Vaginosis ◽

Human Papilloma Virus Infection ◽

Hpv Infection ◽

High Grade ◽

Squamous Intraepithelial Lesions ◽

Papilloma Virus ◽

Cervical Squamous Intraepithelial Lesions ◽

The Relationship ◽

Intraepithelial Lesions

ABSTRACT Objectives Human papillomavirus (HPV) is known to be associated with squamous intraepithelial lesions (SILs). However, there is limited and conflicting literature on the relationship between bacterial vaginosis (BV) and SIL. The aim of this study is to determine the prevalence of BV and evaluate the association between BV and SIL. Methods A retrospective study was performed on 10,546 cases between 2012 and 2017. HPV results were available in 7,081 cases. Results BV was present in 17.6% of cases. There was significant association between BV, positive HPV infection, and high-grade SIL. BV patients with negative HPV infection showed more squamous abnormalities than BV-negative HPV-negative patients. Conclusions We found there is a significant association between BV and SIL. BV is more common among patients with HPV infection and is independently associated with squamous abnormalities in cervical smears and surgical follow-up.

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Enhanced disease progression due to persistent HPV-16/58 infections in Korean women: a systematic review and the Korea HPV cohort study

Virology Journal ◽

10.1186/s12985-021-01657-2 ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Jaehyun Seong ◽

Sangmi Ryou ◽

JeongGyu Lee ◽

Myeongsu Yoo ◽

Sooyoung Hur ◽

...

Keyword(s):

Cohort Study ◽

Disease Progression ◽

Hpv Infection ◽

High Grade ◽

Squamous Intraepithelial Lesions ◽

Hpv 16 ◽

Persistent Infections ◽

Hpv Prevalence ◽

Risk Of Disease ◽

Intraepithelial Lesions

Abstract Background Persistent human papillomavirus (HPV) infection is a key factor for the development and progression of cervical cancer. We sought to identify the type-specific HPV prevalence by cervical cytology and assess disease progression risk based on high-risk persistent HPV infection in South Korea. Methods To investigate the HPV prevalence by Pap results, we searched seven literature databases without any language or date restrictions until July 17, 2019. To estimate the risk of disease progression by HPV type, we used the Korea HPV Cohort study data. The search included the terms “HPV” and “Genotype” and “Korea.” Studies on Korean women, type-specific HPV distribution by cytological findings, and detailed methodological description of the detection assay were included. We assessed the risk of disease progression according to the high-risk HPV type related to the nonavalent vaccine and associated persistent infections in 686 HPV-positive women with atypical squamous cells of uncertain significance or low-grade squamous intraepithelial lesions from the Korea HPV Cohort Study. Type-specific HPV prevalence was the proportion of women positive for a specific HPV genotype among all HPV-positive women tested for that genotype in the systematic review. Results We included 23 studies in our review. HPV-16 was the most prevalent, followed by HPV-58, -53, -70, -18, and -68. In women with high-grade squamous intraepithelial lesions, including cancer, HPV-16, -18, and -58 were the most prevalent. In the longitudinal cohort study, the adjusted hazard ratio of disease progression from atypical squamous cells of uncertain significance to high-grade squamous intraepithelial lesions was significantly higher among those with persistent HPV-58 (increase in risk: 3.54–5.84) and HPV-16 (2.64–5.04) infections. Conclusions While HPV-16 was the most prevalent, persistent infections of HPV-16/58 increased the risk of disease progression to high-grade squamous intraepithelial lesions. Therefore, persistent infections of HPV-16 and -58 are critical risk factors for cervical disease progression in Korea. Our results suggest that equal attention should be paid to HPV-58 and -16 infections and provide important evidence to assist in planning the National Immunization Program in Korea.

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Enhanced disease progression due to persistent HPV-16/58 infections in Korean women: A systematic review and the Korea HPV cohort study

10.21203/rs.3.rs-503978/v1 ◽

2021 ◽

Author(s):

Jaehyun Seong ◽

Sangmi Ryou ◽

JeongGyu Lee ◽

Myeongsu Yoo ◽

Sooyoung Hur ◽

...

Keyword(s):

Cohort Study ◽

Disease Progression ◽

Hpv Infection ◽

High Grade ◽

Squamous Intraepithelial Lesions ◽

Hpv 16 ◽

Persistent Infections ◽

Hpv Prevalence ◽

Risk Of Disease ◽

Intraepithelial Lesions

Abstract Background Persistent human papillomavirus (HPV) infection is a key factor for the development and progression of cervical cancer. We sought to identify the type-specific HPV prevalence by cervical cytology and assess disease progression risk based on high-risk persistent HPV infection in South Korea. Methods To investigate the HPV prevalence by Pap results, we searched seven literature databases without any language or date restrictions until July 17, 2019. To estimate the risk of disease progression by HPV type, we used the Korea HPV Cohort study data. The search included the terms “HPV” and “Genotype” and “Korea.” Studies on Korean women, type-specific HPV distribution by cytological findings, and detailed methodological description of the detection assay were included. We assessed the risk of disease progression according to the high-risk HPV type related to the nonavalent vaccine and associated persistent infections in 686 HPV-positive women with atypical squamous cells of uncertain significance or low-grade squamous intraepithelial lesions from the Korea HPV Cohort Study. Type-specific HPV prevalence was the proportion of women positive for a specific HPV genotype among all HPV-positive women tested for that genotype in the systematic review. Results We included 23 studies in our review. HPV-16 was the most prevalent, followed by HPV-58, -53, -70, -18, and − 68. In women with high-grade squamous intraepithelial lesions, including cancer, HPV-16, -18, and − 58 were the most prevalent. In the longitudinal cohort study, the adjusted hazard ratio of disease progression from atypical squamous cells of uncertain significance to high-grade squamous intraepithelial lesions was significantly higher among those with persistent HPV-58 (increase in risk: 3.54 to 5.84) and HPV-16 (2.64 to 5.04) infections. Conclusions While HPV-16 was the most prevalent, persistent infections of HPV-16/58 increased the risk of disease progression to high-grade squamous intraepithelial lesions. Therefore, persistent infections of HPV-16 and − 58 are critical risk factors for cervical disease progression in Korea. Our results suggest that equal attention should be paid to HPV-58 and − 16 infections and provide important evidence to assist in planning the National Immunization Program in Korea.

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The CpG island methylator phenotype increases the risk of high-grade squamous intraepithelial lesions and cervical cancer

Clinical Epigenetics ◽

10.1186/s13148-021-01224-0 ◽

2022 ◽

Vol 14 (1) ◽

Author(s):

Jaqueline Loaeza-Loaeza ◽

Berenice Illades-Aguiar ◽

Oscar del Moral-Hernández ◽

Yaneth Castro-Coronel ◽

Marco A. Leyva-Vázquez ◽

...

Keyword(s):

Cervical Cancer ◽

Dna Methylation ◽

Cpg Island ◽

Hpv Infection ◽

Low Grade ◽

High Grade ◽

Squamous Intraepithelial Lesions ◽

Cpg Island Methylator Phenotype ◽

Methylator Phenotype ◽

Intraepithelial Lesions

Abstract Background High-risk human papillomavirus (HR-HPV) infection is the main cause of cervical cancer, but additional alterations are necessary for its development. Abnormal DNA methylation has an important role in the origin and dissemination of cervical cancer and other human tumors. In this work, we analyzed the methylation of eight genes (AJAP1, CDH1, CDH13, MAGI2, MGMT, MYOD1, RASSF1A and SOX17) that participate in several biological processes for the maintenance of cell normality. We analyzed DNA methylation by methylation-specific PCR (MSP) and HPV infection using the INNO‑LiPA genotyping kit in 59 samples diagnostic of normal cervical tissue (non-SIL), 107 low-grade squamous intraepithelial lesions (LSILs), 29 high-grade squamous intraepithelial lesions (HSILs) and 51 cervical cancers (CCs). Results We found that all samples of LSIL, HSIL, and CC were HPV-positive, and the genotypes with higher frequencies were 16, 18, 51 and 56. In general, the genes analyzed displayed a significant tendency toward an increase in methylation levels according to increasing cervical lesion severity, except for the CDH13 gene. High CpG island methylator phenotype (CIMP) was associated with a 50.6-fold (95% CI 4.72–2267.3)-increased risk of HSIL and a 122-fold risk of CC (95% CI 10.04–5349.7). Conclusions We found that CIMP high was significantly associated with HSIL and CC risk. These results could indicate that CIMP together with HR-HPV infection and other factors participates in the development of HSIL and CC.

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Anogenital warts contributing to the risk of squamous intraepithelial lesions among HIV-positive women of São Paulo, Brazil

International Journal of STD & AIDS ◽

10.1258/095646203321605503 ◽

2003 ◽

Vol 14 (5) ◽

pp. 309-313 ◽

Cited By ~ 2

Author(s):

Maria Alice G Goncalves ◽

Marcelo N Burattini ◽

Eduardo A Donadi ◽

Eduardo Massad

Keyword(s):

Univariate Analysis ◽

Hpv Infection ◽

Hiv Positive ◽

High Grade ◽

Anogenital Warts ◽

Squamous Intraepithelial Lesions ◽

Cross Sectional ◽

Hpv Dna ◽

Hiv Positive Women ◽

Intraepithelial Lesions

Unsafe sexual practices may expose HIV-positive women to high-grade squamous intraepithelial lesions (SIL) and to infection with oncogenic human papillomavirus (HPV) types. A cross sectional study of 141 HIV-positive women was designed to evaluate risk factors for the development of cervico-vaginal SIL and HPV-DNA detection/typing. Uni- and multivariate forward stepwise analysis was used to determine the relationship between risk variables and HPV infection and between risk behaviour, HPV and HIV infection with development of SIL. Univariate analysis showed that HPV-DNA infection was related to previous and recurrent anogenital warts, male genital warts and cytological alteration. For final multivariate analysis, both HPV type (undetermined- and high-risk, OR=29.3 and 112.0, respectively) were statistically associated ( P=0.019) with high-grade cervico-vaginal SIL. The presence of anogenital warts as well as high- and undetermined-risk HPV infection may alert to cyto/histopathological alterations. These results point out the importance of the use of barrier methods and routine early genitoscopy/treatment for HIV-infected partners.

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Do Infection Patterns of Human Papillomavirus Affect the Cytologic Detection of High-Grade Cervical Lesions on Papanicolaou Tests?

Archives of Pathology & Laboratory Medicine ◽

10.5858/arpa.2016-0478-oa ◽

2017 ◽

Vol 142 (3) ◽

pp. 347-352 ◽

Cited By ~ 6

Author(s):

Siavash Azadmanesh Samimi ◽

Roxanne R. Mody ◽

Steven Goodman ◽

Eric Luna ◽

Donna Armylagos ◽

...

Keyword(s):

Hpv Infection ◽

Low Grade ◽

Lower Grade ◽

High Grade ◽

Squamous Intraepithelial Lesions ◽

Cervical Lesions ◽

Atypical Squamous Cell ◽

Intraepithelial Lesion ◽

Intraepithelial Lesions ◽

Hpv 18

Context.— Persistent infection with high-risk human papillomavirus (hrHPV) is the major cause of cervical cancer. The effect of HPV infection patterns on cytologic detection of cervical lesions is unknown. Objective.— To determine the effect of HPV infection patterns on the sensitivity of cytologic detection of high-grade cervical lesions. Design.— Papanicolaou tests from 257 women with biopsy-confirmed, high-grade squamous intraepithelial lesions were analyzed with respect to HPV infection patterns. Results.— Among 257 biopsy-confirmed, high-grade squamous intraepithelial lesion cases, the preceding cytology showed 20 cases (8%) were benign; 166 cases (65%) were low-grade cervical lesions, including atypical squamous cell of undetermined significance and low-grade squamous intraepithelial lesions; and 71 cases (28%) were high-grade cervical lesions, including atypical squamous cells cannot rule out high-grade squamous intraepithelial lesion (atypical squamous cell–high), atypical glandular cells, and high-grade squamous intraepithelial lesions. In 236 cases tested for HPV, those exhibiting low-grade cervical lesions on cytology were often associated with coinfections of mixed hrHPV genotypes (31 of 40; 78%) or non-16/18 hrHPV (75/103; 73%), compared with single-genotype infections of HPV-16 (33 of 62; 53%) or HPV-18 (2 of 6; 33%) (P = .001). In contrast, high-grade cervical lesion cytomorphology tended to associate with the single-genotype infection of HPV-16 (20 of 62; 32%) or HPV-18 (3 of 6; 50%), compared with non-16/18 hrHPV (25 of 103; 24%) or multigenotype infection (8 of 40; 20%) (P = .01). Conclusions.— Our findings suggest that multigenotypic or non-16/18 hrHPV infections often produce deceptive lower-grade cytomorphology, which could result in underdiagnosis and delay of treatment. The HPV infection patterns may offer unrecognized benefit beyond HPV genotyping and should be considered during clinical risk evaluation of women with lower-grade cytology.

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A phase II trial of the use of 4,4’-dihydroxybenzophenone-2,4-dinitrophenyl-hydrazone (A-007) topical gel in the treatment of high-grade squamous intraepithelial lesions (HSIL) of the cervix

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.5593 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 5593-5593 ◽

Cited By ~ 2

Author(s):

D. Muñoz ◽

D. Cantu ◽

A. Gonzalez ◽

A. Meneses ◽

A. Mohar ◽

...

Keyword(s):

Pap Smear ◽

Response Rate ◽

The United States ◽

Hpv Infection ◽

Pathological Response ◽

High Grade ◽

Squamous Intraepithelial Lesions ◽

Topical Gel ◽

Independent Expert ◽

Intraepithelial Lesions

5593 Background: The incidence of cervical cancer is highly correlated with cervical high grade squamous intraepithelial lesions (HSIL [CIN2/3]) and human papillomavirus (HPV) infection in men and women. Approximately 70 - 80% of sexually active adolescents and adults will become infected with HPV during their lifetime. In 2003 alone, there were 50 million cases of HPV infections in the United States. Our main objective is to determine the pathological response (complete and partial, based on independent review panel of two patho the uterine cervix of women with HSIL [CIN 2/3]. Materials and Methods: Following colposcopy, pap smear and biopsy confirmation of HSIL (CIN 2/3) and HPV infection status, women are treated with gel applied to the cervix via an intravaginal applicator once daily for 5 consecutive days of a 28-day cycle for 2 cycles. At month 4 post enrollment into the trial, all women undergo the loop electrosurgical excision procedure (LEEP) procedure and repeated virology assessment. Results: 65 patients were enrolled at 2 centers and completed treatment with A-007 and 100% (65/65) were HPV positive (81.5% by Hibrid Capture II for High Risk and 100% PCR positive). All baseline and LEEP pathological specimens will be blinded read by a panel of two independent expert pathologists. A subject will be considered a complete pathological responder (CR) when the patient has regression of HSIL (CIN 2/3) without pathological evidence of HSIL, and a partial pathological responder (PR) when she has regression of HSIL (CIN 2/3) to LSIL (CIN 1). Overall response rate is defined as the percentage of patients with CR and PR. To date, no serious adverse events (SAE) has been reported during treatment in all enrolled patients, only has been reported a moderate local and transitory itching/burning sensation during the first 5–20 minutes after application in 18% (12/65) of the cases. At this moment LEEP procedures are being scheduled for all patients and the pathological response rate as well as the HPV response rate will be available and presented at the conference. [Table: see text]

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