scholarly journals Changes in the Proteome in the Development of Chronic Human Papillomavirus Infection—A Prospective Study in HIV Positive and HIV Negative Rwandan Women

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 5983
Author(s):  
Emile Bienvenu ◽  
Marie Francoise Mukanyangezi ◽  
Stephen Rulisa ◽  
Anna Martner ◽  
Bengt Hasséus ◽  
...  

Background: Effects on the proteome when a high risk (HR)-HPV infection occurs, when it is cleared and when it becomes chronic were investigated. Moreover, biomarker panels that could identify cervical risk lesions were assessed. Methods: Cytology, HPV screening and proteomics were performed on cervical samples from Rwandan HIV+ and HIV- women at baseline, at 9 months, at 18 months and at 24 months. Biological pathways were identified using the String database. Results: The most significantly affected pathway when an incident HR-HPV infection occurred was neutrophil degranulation, and vesicle-mediated transport was the most significantly affected pathway when an HR-HPV infection was cleared; protein insertion into membrane in chronic HR-HPV lesions and in lesions where HR-HPVs were cleared were compared; and cellular catabolic process in high-grade lesions was compared to that in negative lesions. A four-biomarker panel (EIF1; BLOC1S5; LIMCH1; SGTA) was identified, which was able to distinguish chronic HR-HPV lesions from cleared HR-HPV/negative lesions (sensitivity 100% and specificity 91%). Another four-biomarker panel (ERH; IGKV2-30; TMEM97; DNAJA4) was identified, which was able to distinguish high-grade lesions from low-grade/negative lesions (sensitivity 100% and specificity 81%). Conclusions: We have identified the biological pathways triggered in HR-HPV infection, when HR-HPV becomes chronic and when cervical risk lesions develop. Moreover, we have identified potential biomarkers that may help to identify women with cervical risk lesions.

Sexual Health ◽  
2012 ◽  
Vol 9 (6) ◽  
pp. 562 ◽  
Author(s):  
Jennifer Margaret Roberts ◽  
Deborah Ekman

Our understanding of the human papillomavirus (HPV) related cytomorphology and histopathology of the anal canal is underpinned by our knowledge of HPV infection in the cervix. In this review, we utilise cervical reporting of cytological and histological specimens as a foundation for the development of standardised and evidence-based terminology and criteria for reporting of anal specimens. We advocate use of the Australian Modified Bethesda System 2004 for reporting anal cytology. We propose the use of a two-tiered histological reporting system for noninvasive disease – low-grade and high-grade anal intraepithelial neoplasia. These classification systems reflect current understanding of the biology of HPV and enhance diagnostic reproducibility. Biomarkers such as p16INK4A may prove useful in further improving diagnostic accuracy. Standardisation is important because it will increase the value of the data collected as Australian centres develop programs for screening for anal neoplasia.


2022 ◽  
Vol 12 ◽  
Author(s):  
Lina Zhang ◽  
Xinyi Shi ◽  
Qing Zhang ◽  
Zhilei Mao ◽  
Xiaoyu Shi ◽  
...  

High-risk human papillomavirus (HPV) infection is the cause of almost all cervical cancers. HPV16 is one of the main risk subtypes. Although screening programs have greatly reduced the prevalence of cervical cancer in developed countries, current diagnostic tests cannot predict if mild lesions may progress into invasive lesions or not. In the current cross-sectional and longitudinal clinical study, we found that the HPV16 E7-specific T cell response in peripheral blood mononuclear cells of HPV16-infected patients is related to HPV16 clearance. It contributes to protecting the squamous interaepithelial lesion (SIL) from further malignant development. Of the HPV16 infected women enrolled (n = 131), 42 had neither intraepithelial lesion nor malignancy (NILM), 33 had low-grade SIL, 39 had high-grade SIL, and 17 had cervical cancer. Only one of 17 (5.9%) cancer patients had a positive HPV16 E7-specific T cell response, dramatically lower than the groups of precancer patients. After one year of follow-up, most women (28/33, 84.8%) with persistent HPV infection did not exhibit a HPV16 E7-specific T cell response. Furthermore, 3 malignantly progressed women, one progressed to high-grade SIL and two progressed to low-grade SIL, were negative to the HPV16 E7-specific T cell response. None of the patients with a positive HPV16 E7-specific T cell response progressed to further deterioration. Our observation suggests that HPV16 E7-specific T cell immunity is significant in viral clearance and contributes in protection against progression to malignancy.


1994 ◽  
Vol 5 (5) ◽  
pp. 343-345 ◽  
Author(s):  
K A Ward ◽  
J R Houston ◽  
B E Lowry ◽  
R D Maw ◽  
W W Dinsmore

212 females attending a genitourinary medicine (GUM) clinic with first episode anogenital warts were screened by cervical cytology and colposcopy/histology for the presence of cervical epithelial abnormalities in keeping with infection by the human papillomavirus (HPV infection) and/or cervical intraepithelial neoplasia (CIN). The prevalence of cervical epithelial abnormalities detected by cervical cytology alone was 32%, rising to 56% after colposcopic examination. However, the majority of cervical lesions detected by colposcopy alone were of low grade (HPV infection and/or CIN I). Histologically confirmed high grade cervical lesions (CIN II or CIN III) were detected more frequently in those females in whom cervical cytological examination indicated dyskaryosis in keeping with any grade of CIN, compared to females without dyskaryotic changes on cervical smear ( P<0.05, chi-squared test with Yates' correction). Early colposcopy is indicated for females with anogenital warts in the presence of a cervical smear showing dyskaryosis in keeping with any grade of CIN, because of the statistically significant increased risk of detecting a potentially progressive high grade cervical lesion. In females without dyskaryotic changes on cervical smear, the value of early colposcopy is uncertain and warrants larger more long-term trials.


2021 ◽  
Vol 1 (1) ◽  
Author(s):  
Akel Randa

Objective: Review the results of anal assessments in women with vulval HSIL with a potential increased risk of anal HSIL, due to HIV status, macroscopic perianal lesions or vaginal/cervical intrepithelial neoplasia. Methods: Ten year retrospective review of 402 anoscopy encounters from 130 patient, who were at higher risk of anal HSIL and underwent anoscopy. Of those, only 13 women had vulval HSIL and were included. Results: Cohort mean age 51 years, 54% smoked, 15% were living with HIV, 31% had additional vaginal or cervical HPV related pathology and 77% were referred with macroscopic perianal lesions. Over half (54%) had anal biopsies demonstrating HSIL, all of whom had visible pathology.Anal cytology was available for 12 cases, varying from HPV infection (42%), HG dyskaryosis (25%) to low grade dyskaryosis (17%). The entire cohort had either anal HSIL or HPV changes and received treatment: Imiquimod (69%), laser ablation (54%), surgical excision (38%), cryotherapy (31%), electrocautery (15%) or Trichloroacetic acid (15%). Conclusion: HSIL of the vulva with visible perianal lesions must prompt anoscopy, as anal cytology specificity and sensitivity is inadequate. Vulval services should secure multi-specialty links for screening and treating HPV pathology and neoplasia, which may arise in different anatomical sites.


2015 ◽  
Vol 193 (4S) ◽  
Author(s):  
Thomas Hermanns ◽  
Ekaterina Olkhov-Mitsel ◽  
Andrea Savio ◽  
Bethany Gill ◽  
Jenna Sykes ◽  
...  

2022 ◽  
Vol 14 (1) ◽  
Author(s):  
Jaqueline Loaeza-Loaeza ◽  
Berenice Illades-Aguiar ◽  
Oscar del Moral-Hernández ◽  
Yaneth Castro-Coronel ◽  
Marco A. Leyva-Vázquez ◽  
...  

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.


Author(s):  
Laurențiu Pirtea ◽  
Dorin Grigoraş ◽  
Petru Matusz ◽  
Marilena Pirtea ◽  
Lavinia Moleriu ◽  
...  

Background. Persistent human papillomavirus (HPV) infection is a necessary event in cervical cancer tumorigenesis. Our objectives were to estimate the rate of HPV infection persistence after large loop excision of the transformation zone (LEEP) in patients with high grade squamous intraepithelial lesions (HSIL) and to investigate if HPV persistence is type related.Methods. We conducted a prospective study on 89 patients with HSIL treated with LEEP. DNA HPV was performed before surgery and at 6, 12, and 18 months after LEEP.Results. Four patients were excluded from the study. The HPV persistence in the remaining 85 patients was 32.95% (6 months), 14.12% (12 months), and 10.59% (18 months). Type 16 had the highest persistence rate, 23.5% (6 months), 11.8% (12 months), and 8.2% (18 months). Coinfection was found to be 54.12% before LEEP and 18.8% (6 months), 4.7% (12 months), and 3.5% (18 months) after LEEP. The rate of coinfections including type 16 was 46.83% of all coinfections. Coinfection including type 16 was not correlated with higher persistence rate compared to infection with type 16 only.Conclusions. HPV infection is not completely eradicated by LEEP in patients with HSIL lesion on PAP smear. HPV persistence after LEEP is influenced by HPV type. HPV type 16 has the highest persistence rate.


2011 ◽  
Vol 21 (9) ◽  
pp. 1654-1663 ◽  
Author(s):  
Maribel Almonte ◽  
Catterina Ferreccio ◽  
Miguel Gonzales ◽  
Jose Manuel Delgado ◽  
C. Hilary Buckley ◽  
...  

ObjectiveTo evaluate the association between potential risk factors for high-risk human papillomavirus (HR-HPV) infection and cofactors for cervical intraepithelial lesions grade 2 or worse (CIN2+) in women attending cervical screening in Amazonian Peru.Materials and MethodsParticipants completed a risk factor questionnaire before screening. High-risk human papillomavirus infection was determined by Hybrid Capture II. Logistic regression was used to evaluate associations between potential risk factors for HR-HPV infection and between cofactors and risk of CIN2+ among women with HR-HPV infection.ResultsScreening and questionnaires were completed by 5435 women aged 25 to 49 years. The prevalence of HR-HPV was 12.6% (95% confidence interval [CI], 11.8%–13.6%) and decreased by age. Early age at first sexual intercourse and several lifetime sexual partners increased the risk of having HR-HPV (age-adjusted odds ratio [AOR] of age at first sexual intercourse <18 vs ≥20, 1.5; 95% CI, 1.2–2.0; AOR of ≥5 lifetime sexual partners vs 1, 2.1; 95% CI, 1.4–3.2). Among women with HR-HPV infection, those with no schooling (AOR relative to 1–5 years of schooling, 3.2; 95% CI, 1.3–8.3) and those with parity ≥3 (AOR relative to parity <3, 2.6; 95% CI, 1.4–4.9) were at increased risk of CIN2+. The effect of parity was stronger for cancer (AOR of parity ≥3 vs <3, 8.3; 95% CI, 1.0–65.6). Further analysis showed that the association between parity and CIN2+ was restricted to women younger than 40. Most women (83%) had previously been screened. Sixty-four percent of CIN2+ cases detected in this study occurred in women who reported having had a Papanicolaou test in the previous 3 years. Only 4 of 20 cancers were detected in women never screened before. Having had a previous abnormal Papanicolaou test increased the risk of CIN2+ (OR, 16.1; 95% CI, 6.2–41.9).ConclusionAmong women with HR-HPV, high parity (in young women), no schooling, lack of good-quality screening and of adequate follow-up care are the main risk factors for high-grade cervical disease in Peru.


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