scholarly journals Viral load and interaction of HPV oncoprotein E6 and E7 with host cellular markers in the progression of cervical cancer

2021 ◽  
Vol 8 (3) ◽  
pp. 184-192
Author(s):  
Bilal Ahmad Mir ◽  
◽  
P. F. Rahaman ◽  
Arif Ahmad ◽  

<abstract> <p>Cervical cancer is the sequel of a multi-factorial, long-term unresolved disease that includes genetic, epigenetic, and viral components responsible for its development and progression. It is the second most common cancer of females in India. Human papillomavirus (HPV) is considered the primary causative agent of pre-neoplastic and cancerous lesions and 90% of all cervical carcinomas are linked to high-risk HPV type 16 and type 18. Although most HR-HPV infections are asymptomatic, transient, and self-limiting, the persistent infection with a high risk (HR-HPV) may cause precancerous lesions that can progress to cervical cancer. HPV type 16 is the most common HPV in India associated with more than 75% of cervical cancer, followed by HPV type 18 and other high-risk types. Infection with HPV alone is not sufficient for the development of cervical cancer but there is the involvement of some host genetic factors also that are responsible for the development and progression of cervical cancer. This article briefly reviews molecular pathogenesis, viral load, and the interaction of HPV oncoprotein E6 and E7 with host cellular markers in the progression of cervical cancer.</p> </abstract>

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Zhiling Wang ◽  
Ying Gu ◽  
Hui Wang ◽  
Junyu Chen ◽  
Yawen Zheng ◽  
...  

Abstract Background To investigate distributions of cervical lesions and factors associated with the severity of the cervical lesions in high-risk HPV (hr-HPV) positive women with atypical squamous cells of undetermined significance (ASC-US) cytology. Methods Clinical information of 250,000 women who underwent HPV and cytological test was collected from January 2012 to January 2019. The association between the severity of the cervical lesions and hr-HPV genotypes, hr-HPV viral load, and ages, were analyzed in hr-HPV-positive/ASC-US women. Results 3459 hr-HPV-positive/ASC-US women were enrolled in this study. Overall, 43.51% of women with ASC-US had normal histological results, 34.35% had high-grade squamous intraepithelial lesion (HSIL), and 1.30% had cervical cancer. The rate of HSIL or worse (HSIL+) in women with single HPV16 infection (63.09%) was the highest, followed by HPV33 (57.50%), HPV51 (36.11%), HPV58 (36.11%), HPV52 (28.28%), HPV18 (26.37%), HPV66 (19.35%), HPV39 (18.92%), HPV53 (15.00%), and HPV56 (8.51%). Detection rate of HSIL+ in low, intermediate and high viral-load groups were 15.87% (n = 30), 34.91% (n = 74) and 40.68% (n = 214) (Cochran-Armitage Trend test χ2 = 35.03, p < 0.0001). Compared with the 51–60-year-old group (21.65%), the women in ≤ 30 (40.52%), 31–40 (39.67%), and 41–50 (34.22%) year-old groups had significantly higher risk of HSIL+. The women in ≤ 51–60 (2.68%) and > 60 (3.41%) year-old groups were at increased risk for cervical cancer, compared with the ≤ 30-year-old group (0.61%). Conclusions ASC-US women with HPV 16/18/33/51/52/58 single infection and multiple infections, as well as high HPV viral loads, have high risk of HSIL+.


2011 ◽  
Vol 6 (1) ◽  
pp. 31-44
Author(s):  
Indra Balachandran

High-risk human papillomavirus (HPV) infection and viral persistence is a major risk factor in the development of squamous intraepithelial lesions and invasive carcinoma of the cervix. In the United States, deaths due to squamous cell carcinoma of the cervix have fallen by 75% since the 1960s because of Papanicolaou (Pap) smear screening. However, the traditional Pap had a sensitivity of about 70% for detecting clinically significant precancerous lesions and cancer because of sampling and interpretive errors. The introduction of 2 liquid-based Pap smear collection systems in the 1990s, the use of HPV testing as a triage and co-testing with Pap smear, and the introduction of 2 automated screening devices have had a significant impact on improving the detection of such precancerous lesions. This review provides an analysis of the changes in Pap smear collection, improvements in screening, the evolutionary changes of high-risk HPV testing, reporting terminology of Pap smears, and clinical management guidelines. The future impact of 2 prophylactic HPV vaccines on the incidence of cervical carcinoma is also discussed. This article also discusses alternatives such as primary screening for high-risk HPV testing with visual inspection for cervical cancer detection used in resource-poor settings with a high incidence of cervical cancer.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yi Hao ◽  
Ming Ye ◽  
Xiaona Chen ◽  
Hongli Zhao ◽  
Ayshamgul Hasim ◽  
...  

Abstract Background To validate markers for cervical carcinoma (CC) and precancerous lesions related with HPV infections. Methods Three different cervical cancer cell lines C-33A, SiHa and Caski were used for secretome profiling by label-free quantitative proteomics. Cervical exfoliated cells and matching serum samples were collected from 284 patients with normal control (n = 75, 26.41 %), precancerous lesions (n = 88, 30.99 %) and early stage cervical squamous carcinoma (n = 121, 42.61 %). HPV subtyping and quantification was performed by PCR and hybridization. 20 candidate proteins identified in previous screening studies (tissue, plasma, cells) were quantified by ELISA. Finally, highly quantitative parallel reaction monitoring mass spectrometry was used to assess the specificities and sensitivities of candidate serum markers. Results While CC was found to be associated with high-risk HPV subtypes, serum antibodies for high risk HPV were not significantly related to the progression of cervical cancer. Significant differences between patient groups were detected for the four proteins CLU, APOA4, APOE and MLH3, but none would allow clinical application due to insufficient sensitivity and specificity and large variability. Subsequent proteomic secretome analysis of cervical cancer cell lines identified a set of 729 common proteins. Cross referencing this dataset with ELISA measurements revealed six candidate proteins of which two, FBLN1 and ANT3, showed co-occurrence with HPV infection (75.7 % and 85 %, respectively) and had promising diagnostic ability in terms of sensitivity and specificity. After the loss of E6/E7 by using CRISPR/Cas9 gene editing, the content of ANT3 and FBLN1 in KoE6/E7 SiHa were downregulated, which indicated the expression of ANT3 and FBLN1 in cervical cancer may be affected by HPV infection. Conclusions FBLN1 and ANT3 might be potential tumor- and HPV-associated serum markers.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yang Liu ◽  
Changjun Xu ◽  
Jing Pan ◽  
Chunyi Sun ◽  
Honglin Zhou ◽  
...  

Abstract Background The significance of HPV viral load in the detection of cervical lesions is still controversial. This study analyzed the correlation between the high-risk HPV viral load and different cervical lesion degrees. Methods This retrospective study included women positive for high-risk HPV DNA and screened for cervical lesions between 01/2015 and 06/2018. The high-risk HPV DNA load was measured by the second-generation Hybrid Capture technology and classified as low, moderate, and high. Colposcopy and biopsy were performed in all patients. The patients were grouped as normal, cervical intraepithelial neoplasia (CIN) grade 1, CIN grade 2, CIN grade 3, and cervical cancer. Multivariable logistic regression was performed to explore the association between high-risk HPV DNA load and cervical lesions. The odds ratios (ORs) represent the odds for increasing from low to high viral load. Results Finally, 265 patients were grouped as normal (n = 125), CIN 1 (n = 51), CIN 2 (n = 23), CIN 3 (n = 46), and cervical cancer (n = 20). Among them, 139 (52.5%) had a low viral load, 90 (34.0) had a moderate viral load, and 36 (13.4%) had a high viral load. Taking the normal control group as a reference, a high viral load was an independent factor for CIN 1 (OR = 3.568, 95% CI: 1.164–10.941, P = 0.026), CIN 2 (OR = 6.939, 95% CI: 1.793–26.852, P = 0.005), CIN 3 (OR = 7.052, 95% CI: 2.304–21.586, P = 0.001), and cervical cancer (OR = 8.266, 95% CI: 2.120–32.233, P = 0.002). Conclusions Among women who underwent cervical biopsy, higher high-risk HPV viral load in cervical lesions was associated with a higher risk of high-grade cervical lesions.


2019 ◽  
Author(s):  
Zhiling Wang ◽  
Ying Gu ◽  
Hui Wang ◽  
Junyu Chen ◽  
Yawen Zheng ◽  
...  

Abstract Objective To investigate distributions of cervical lesions and factors associated with the severity of the cervical lesions in high-risk HPV (hr-HPV) positive women with ASC-US cytology.Methods Clinical information of 250,000 women who underwent HPV and cytological test was collected from January 2012 to January 2019. The association between the severity of the cervical lesions and hr-HPV genotypes, hr-HPV viral load, and ages, were analyzed in hr-HPV-positive/ASC-US women.Results 3459 hr-HPV-positive/ASC-US women were enrolled in this study. Overall, 43.51% of women with ASC-US had normal histological results, 34.35% had high-grade squamous intraepithelial lesion (HSIL), and 1.30% had cervical cancer. The rate of HSIL or worse (HSIL+) in women with single HPV16 infection (63.09%) was the highest, followed by HPV33 (57.50%), HPV51 (36.11%), HPV58 (36.11%), HPV52 (28.28%), HPV18(26.37%), HPV66 (19.35%), HPV39 (18.92%), HPV53 (15.00%), and HPV56 (8.51%). Detection rate of HSIL+ in low, intermediate and high viral-load groups were 15.87% (n=30), 34.91% (n=74) and 40.68% (n=214) (Cochran-Armitage Trend test χ2=35.03, P<0.0001). Compared with the 51-60-year-old group (21.65%), the women in ≤30 (40.52%), 31-40 (39.67%), and 41-50 (34.22%) year-old groups had significantly higher risk of HSIL+. The women in ≤51-60 (2.68%) and >60 (3.41%) year-old groups were at increased risk for cervical cancer, compared with the ≤30-year-old group (0.61%).Conclusion ASC-US women with HPV 16/18/33/51/52/58 single infection and multiple infections, as well as high HPV viral loads, have high risk of HSIL+. Young women and older women have higher HSIL+ detection rates, while the latter has a higher cervical cancer detection rate.


2006 ◽  
Vol 35 (3) ◽  
pp. 264-269 ◽  
Author(s):  
Yuping Wu ◽  
Yulong Chen ◽  
Longyu Li ◽  
Guifang Yu ◽  
Yanling Zhang ◽  
...  

2019 ◽  
Author(s):  
Zhiling Wang ◽  
Ying Gu ◽  
Hui Wang ◽  
Junyu Chen ◽  
Yawen Zheng ◽  
...  

Abstract Objective To investigate distributions of cervical lesions and factors associated with the severity of the cervical lesions in high-risk HPV (hr-HPV) positive women with ASC-US cytology.Methods Clinical information of 250,000 women who underwent HPV and cytological test was collected from January 2012 to January 2019. The association between the severity of the cervical lesions and hr-HPV genotypes, hr-HPV viral load, and ages, were analyzed in hr-HPV-positive/ASC-US women.Results 3459 hr-HPV-positive/ASC-US women were enrolled in this study. Overall, 43.51% of women with ASC-US had normal histological results, 34.35% had high-grade squamous intraepithelial lesion (HSIL), and 1.30% had cervical cancer. The rate of HSIL or worse (HSIL+) in women with single HPV16 infection (63.09%) was the highest, followed by HPV33 (57.50%), HPV51 (36.11%), HPV58 (36.11%), HPV52 (28.28%), HPV18(26.37%), HPV66 (19.35%), HPV39 (18.92%), HPV53 (15.00%), and HPV56 (8.51%). Detection rate of HSIL+ in low, intermediate and high viral-load groups were 15.87% (n=30), 34.91% (n=74) and 40.68% (n=214) (Cochran-Armitage Trend test χ2=35.03, P<0.0001). Compared with the 51-60-year-old group (21.65%), the women in ≤30 (40.52%), 31-40 (39.67%), and 41-50 (34.22%) year-old groups had significantly higher risk of HSIL+. The women in ≤51-60 (2.68%) and >60 (3.41%) year-old groups were at increased risk for cervical cancer, compared with the ≤30-year-old group (0.61%).Conclusion ASC-US women with HPV 16/18/33/51/52/58 single infection and multiple infections, as well as high HPV viral loads, have high risk of HSIL+. Young women and older women have higher HSIL+ detection rates, while the latter has a higher cervical cancer detection rate.


2020 ◽  
Author(s):  
Zhiling Wang ◽  
Ying Gu ◽  
Hui Wang ◽  
Junyu Chen ◽  
Yawen Zheng ◽  
...  

Abstract Background To investigate distributions of cervical lesions and factors associated with the severity of the cervical lesions in high-risk HPV (hr-HPV) positive women with atypical squamous cells of undetermined significance (ASC-US) cytology. Methods Clinical information of 250,000 women who underwent HPV and cytological test was collected from January 2012 to January 2019. The association between the severity of the cervical lesions and hr-HPV genotypes, hr-HPV viral load, and ages, were analyzed in hr-HPV-positive/ASC-US women. Results 3459 hr-HPV-positive/ASC-US women were enrolled in this study. Overall, 43.51% of women with ASC-US had normal histological results, 34.35% had high-grade squamous intraepithelial lesion (HSIL), and 1.30% had cervical cancer. The rate of HSIL or worse (HSIL+) in women with single HPV16 infection (63.09%) was the highest, followed by HPV33 (57.50%), HPV51 (36.11%), HPV58 (36.11%), HPV52 (28.28%), HPV18(26.37%), HPV66 (19.35%), HPV39 (18.92%), HPV53 (15.00%), and HPV56 (8.51%). Detection rate of HSIL + in low, intermediate and high viral-load groups were 15.87% (n = 30), 34.91% (n = 74) and 40.68% (n = 214) (Cochran-Armitage Trend test χ2 = 35.03, P < 0.0001). Compared with the 51-60-year-old group (21.65%), the women in ≤ 30 (40.52%), 31–40 (39.67%), and 41–50 (34.22%) year-old groups had significantly higher risk of HSIL+. The women in ≤ 51–60 (2.68%) and > 60 (3.41%) year-old groups were at increased risk for cervical cancer, compared with the ≤ 30-year-old group (0.61%). Conclusions ASC-US women with HPV 16/18/33/51/52/58 single infection and multiple infections, as well as high HPV viral loads, have high risk of HSIL+.


Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 4149
Author(s):  
Antoine Baumann ◽  
Julie Henriques ◽  
Zohair Selmani ◽  
Aurélia Meurisse ◽  
Quentin Lepiller ◽  
...  

High-risk HPV (hrHPV) testing has been implemented as a primary screening tool for cervical cancer in numerous countries. However, there is still a need for relevant triage strategies to manage hrHPV positive women to avoid excessive referral to colposcopy. The objective of this study was to assess, in women infected by hrHPV and presenting no or mild cytological abnormalities, HPV16 and HPV18 viral loads to predict the development of cervical high-grade lesion. Among 2102 women positive for hrHPV, 885 had no lesion or mild cytological abnormalities at baseline and had at least one follow-up (FU) visit. HPV16 and HPV18 prevalence was 25.9% and 8.4%, respectively. Of those women, 15% developed a high-grade lesion during the FU. An HPV16 viral load cut-off set at 3.2 log10GE/103 cells permitted to identify a subgroup of women at high risk of developing high-grade cervical lesion (HR = 2.67; 95% CI 1.80–3.97; p ≤ 0.0001). No specific HPV18 viral load threshold could have been defined in regard to the present study. In multivariate analysis, HPV16 load (absence/log10GE/103 cells < 3.2 vs. ≥3.2), RLU/PC 239 (1–100 pg/mL vs. >100 pg/mL) and cytology (normal vs abnormal) were independently associated with a significant increased risk of high-grade lesion development and were used to construct the prognostic score. In conclusion, HPV16 load is a relevant biomarker to identify women at high risk for developing cervical precancerous lesions.


2003 ◽  
Vol 16 (1) ◽  
pp. 1-17 ◽  
Author(s):  
Eileen M. Burd

SUMMARY Of the many types of human papillomavirus (HPV), more than 30 infect the genital tract. The association between certain oncogenic (high-risk) strains of HPV and cervical cancer is well established. Although HPV is essential to the transformation of cervical epithelial cells, it is not sufficient, and a variety of cofactors and molecular events influence whether cervical cancer will develop. Early detection and treatment of precancerous lesions can prevent progression to cervical cancer. Identification of precancerous lesions has been primarily by cytologic screening of cervical cells. Cellular abnormalities, however, may be missed or may not be sufficiently distinct, and a portion of patients with borderline or mildly dyskaryotic cytomorphology will have higher-grade disease identified by subsequent colposcopy and biopsy. Sensitive and specific molecular techniques that detect HPV DNA and distinguish high-risk HPV types from low-risk HPV types have been introduced as an adjunct to cytology. Earlier detection of high-risk HPV types may improve triage, treatment, and follow-up in infected patients. Currently, the clearest role for HPV DNA testing is to improve diagnostic accuracy and limit unnecessary colposcopy in patients with borderline or mildly abnormal cytologic test results.


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