Association between human papillomavirus (HPV) 16, HPV18, and other HR‐HPV viral load and the histological classification of cervical lesions: Results from a large‐scale cross‐sectional study

Wu, Zeni; Qin, Yu; Yu, Lulu; Lin, Chunqing; Wang, Hong; Cui, Jianfeng; Liu, Bin; Liao, Yiqun; Warren, De'Andre; Zhang, Xun; Chen, Wen

doi:10.1002/jmv.24645

Cited by 36 publications

(44 citation statements)

References 35 publications

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“…First, integration of HPV16 and HPV18 into the cellular genome may show differences (34). Second, differences are also found in the trends seen for presumptive viral loads from a normal cervix to SCC (35,36). Although evidence above has confirmed that HPV16 acts in malignant transformation differently from HPV18, our data show that the combined positivity rates of HPV16-E6 and HPV18-E6 in HPV16/18 coinfection were similar to their single infections counterparts, suggesting HPV16 and HPV18 might cause cervical lesion independently.…”

Section: Discussionmentioning

confidence: 99%

Human Papillomavirus (HPV) 16/18 E6 Oncoprotein Expression in Infections with Single and Multiple Genotypes

Jiang

et al. 2019

Cancer Prevention Research

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Factors that differentiate risk of cervical cancer associated with infection with single versus multiple HPV types are yet undefined. We hypothesize that E6 oncoprotein is one determining factor. This cross-sectional, multicenter study was performed between 2013 and 2017. A total of 1,781 women were recruited from six hospitals. Samples were tested for presence of 14 types of high-risk HPV DNA. HPV16/18-positive samples were also tested for HPV16/18-E6 oncoprotein. Of 1,781 subjects, 687 (38.6%) tested positive for HPV16/18. HPV16/18 single infections were associated with higher E6 positivity rates compared with multiple infections only for cancer cases (HPV16: 92.2% vs. 76.5%; HPV18: 93.9% vs. 62.1%) but not for normal histopathology or cervical intraepithelial neoplasia. In HPV16/18 coinfection subjects, the positivity rate was 42.9% for HPV16-E6 and 42.9% for HPV18-E6. The combined positivity rate of either HPV16-E6 or HPV18-E6 among HPV16/18 coinfection subjects was 78.6%, similar with HPV16 (74.8%) and HPV18 (79.5%) single-infection subjects. The positivity rates of HPV16/18 E6 oncoprotein varied depending on the HPV-type composition in multiple infection ("clusters") including HPV types other than 16 and 18. Multiple infection clusters most likely to express HPV16-E6 and HPV18-E6 were HPV16/52 (61.5%) and HPV18/52 (66.7%), and the less were HPV16/45 (10.0%) and HPV18/51 (16.7%), respectively. Patterns of E6 oncoprotein expression varied depending on clustering types. However, expression was greatest in women with single HPV-type infections compared with those with multiple HPV types regardless of histopathology. Our findings provided new insight of natural history of cervical cancer.

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Section: Discussionmentioning

confidence: 99%

Human Papillomavirus (HPV) 16/18 E6 Oncoprotein Expression in Infections with Single and Multiple Genotypes

Jiang

et al. 2019

Cancer Prevention Research

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“…Notably, these assays were sufficiently sensitive to detect very low viral copy numbers (0.001 copies/μL) as well as able to detect values as high as 67 million copies/μL. Several previous studies have argued that a linear relationship between the severity of disease and viral load is associated with specific HPV types [15,16,17,18]. One study reported a significant relationship when the HPV types were 16, 31, 33, 52, and 58, while the association was not significant with HPV types 18, 45, 56, and 59 [19].…”

Section: Discussionmentioning

confidence: 99%

Human papillomavirus type 16 and 18 viral loads as predictors associated with abnormal cervical cytology among women in Saudi Arabia

Obeid

Almatrrouk

Khayat

et al. 2020

Heliyon

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The detection of HPV viral DNA is regularly conducted with cervical screening. However, using a molecular marker such as the viral load may serve as a predictor associated with disease detection and progression. The present study aimed to screen for and genotype HPV among women in Saudi Arabia, develop and validate sensitive quantitative polymerase chain reaction (qPCR) assays to detect viral load for the two most common HPV types, namely 16 and 18, and assess whether HPV viral load could be used as a marker for cervical abnormality and disease progression. This study examined 733 specimens (both formalin-fixed paraffin embedded specimens and PAP smear samples) from women who underwent cervical screening. The specimens and samples were processed for DNA extraction and then tested for HPV DNA using nested PCR. Approximately 165 specimens (18%) were positive for HPV. Those specimens were genotyped using a reverse line blotting hybridization assay. The results indicated that the most common HPV types detected were a single infection with HPV 16 (51%) or with HPV 18 (28%) followed by infections with multiple HPV types (~7%). A qPCR TaqMan assay developed and validated in-house was used to determine viral load for HPV genotypes 16 (n ¼ 80) and 18 (n ¼ 45). Viral loads for both HPV types were significantly associated with cervical cytology grade (P < 0.05). The odds ratio (OR) for the HPV 16 viral load was high for specimens with cervical cancer (OR, 18.8; 95% CI, 4.3-82.9) or for those with high-grade squamous intraepithelial lesions (OR, 14.7; 95% Cl,). For the HPV 18 viral load, the OR was significant only for specimens with cervical cancer (OR, 11.1; 95% Cl, 2.2-54.9). Logistic regression models for HPV 16 and for HPV 18 viral load levels were significant, with higher viral load associated with cervical abnormalities. These findings indicate that viral load is a predictor significantly associated with cytology abnormality in women who are positive for high-risk HPVs and suggest that integrating a viral load test into current clinical screening practices for HPV-positive women is warranted in Saudi Arabia.

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“…Since the integration of the HPV DNA into the host cells is necessary for malignant transformation by the E6 and E7 proteins, the HBV DNA load has been suggested to be used as a marker of the risk of dysplasia and CC [17,23]. In addition, the quanti cation of the DNA load could have a direct relationship with the risk of cervical lesions [24][25][26]. Many HPV infections will not lead to cervical lesions since a persistent infection is necessary for malignant transformation, and many infections are self-resolving [27].…”

Section: Discussionmentioning

confidence: 99%

“…Nevertheless, this association is still controversial [21,30]. Lorincz et al [21] reported that there was no association between the viral load of 13 HR-HPVs and the risk of CIN III and CC, while Wu et al [24] showed that the HPV-18 viral load was low in precancerous lesions but high in CC. On the other hand, the present study supports the hypothesis that high HR-HPV viral loads are associated with more advanced cervical lesions.…”

Section: Discussionmentioning

confidence: 99%

Significance of the Viral Load of High-risk Hpv in the Diagnosis and Prediction of Cervical Lesions: A Retrospective Study

Liu

Pan

et al. 2020

Preprint

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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 (HR)-HPV viral load and different cervical lesion degrees.Methods: This was a retrospective study of the patients who first visited the hospital between January 2015 and June 2018. Patients with positive HR-HPV were screening for cervical cancer. The HR-HPV DNA load was measured by the second generation hybrid capture (HC2) technology. The patients grouped as normal, CIN I, CIN II, CIN III, and cervical cancer. Multivariable logistic regression was performed to explore the association between HR-HPV DNA load and cervical lesions.Results: Finally, 265 patients were grouped as normal (n=125), CIN I (n=51), CIN II (n=23), CIN III (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 I (CIN I: OR=3.959, 95%CI: 1.300-12.059, P=0.015) CIN II (OR=6.211, 95%CI: 1.641-23.513, P=0.007), CIN III (OR=7.002, 95%CI: 2.308-21.244, P=0.001), and cervical cancer (OR=9.439, 95%CI: 2.394-37.22, P=0.001).Conclusion: Cervical lesions are closely related to HR-HPV infection. Higher HR-HPV viral load in cervical lesions was associated with a higher risk of high-grade cervical lesions.

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Association between human papillomavirus (HPV) 16, HPV18, and other HR‐HPV viral load and the histological classification of cervical lesions: Results from a large‐scale cross‐sectional study

Cited by 36 publications

References 35 publications

Human Papillomavirus (HPV) 16/18 E6 Oncoprotein Expression in Infections with Single and Multiple Genotypes

Human Papillomavirus (HPV) 16/18 E6 Oncoprotein Expression in Infections with Single and Multiple Genotypes

Human papillomavirus type 16 and 18 viral loads as predictors associated with abnormal cervical cytology among women in Saudi Arabia

Significance of the Viral Load of High-risk Hpv in the Diagnosis and Prediction of Cervical Lesions: A Retrospective Study

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