Prognostic significance of human papillomavirus viral load in correlation with different therapeutic modalities in cervical cancer patients

Cao, Meng; Shah, Walayat; Jingxian, QI; Zhou, Yi; Wang, Yili; Chen, Hongwei

doi:10.1016/j.prp.2016.06.011

Cited by 9 publications

(5 citation statements)

References 20 publications

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“…In order to include cell context information into HPV tests, p16 IHC has been developed as a surrogate marker based on the findings that HPV E7 oncoprotein binds to Rb protein region which leads to p16 overexpression [ 5 ]. In situ detection of HPV E6 and E7 mRNA becomes available after RNAscope technology has been developed [ 6 – 12 ]. As a novel generation of RNA in situ hybridization, this method is designed to detect E6/E7 RNAs of different HPV subtypes, for example, HPV HR-18 has included 18 high risk (HR) of HPV subtypes (HPVs 16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, 73, 82) [ 6 , 10 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

“…In situ detection of HPV E6 and E7 mRNA becomes available after RNAscope technology has been developed [ 6 – 12 ]. As a novel generation of RNA in situ hybridization, this method is designed to detect E6/E7 RNAs of different HPV subtypes, for example, HPV HR-18 has included 18 high risk (HR) of HPV subtypes (HPVs 16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, 73, 82) [ 6 , 10 , 13 ]. The test utilized 10 pairs of oligonucleotide probes per HPV subtype with each oligo-probe carried about 25 base region that bound specifically with an E6 or E7 sequence.…”

Section: Introductionmentioning

confidence: 99%

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Human papillomavirus E6E7 mRNA and TERC lncRNA in situ detection in cervical scraped cells and cervical disease progression assessment

Zhao

Fan

et al. 2022

Virol J

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Background Human papillomavirus screen in female cervical cells has demonstrated values in clinical diagnosis of precancerous lesions and cervical cancers. Human papillomavirus tests of cervical cells by utilizing Polymerase Chain Reaction (PCR) method provides human papillomavirus infection status however no further virus in situ information. Although it is well known that the tests of human papillomavirus E6/E7 RNA location in infected cervical cells and cell internal malignancy molecular will provide clues for gynecologists to evaluate disease progression, there are technique difficulties to preserve RNAs in cervical scraped cells for in situ hybridization. Methods In current study, after developing a cervical cell collection and preparation method for RNA in situ hybridization, we captured the chance to screen 98 patient cervical cell samples and detected human papillomavirus E6/E7 mRNAs of high-risk subtypes, low-risk subtypes and long non-coding RNA (lncRNA) TERC in the cells. Results There were 69 samples exhibited consistence between human papillomavirus PCR and human papillomavirus RNA in situ hybridization results in cervical collected cells. Among them, 23 were both positive and 46 were both negative. In the rest 29 samples, 8 were HPV RNAscope positive, either high risk or low risk subtypes, however HPV PCR negative. Another 9 samples were HPV PCR results positive whereas RNAscope negative. The last 12 samples were HPV positive detected by both RNAscope and PCR methods, however inconsistent between high-risk and low-risk subtypes. In RNAscope positive samples, viral E6/E7 mRNAs were observed to distribute in cervical scraped cell nucleus and cytoplasm. Moreover, HPV viral RNA gathered clusters were observed outside of cells through human papillomavirus RNA in situ hybridization detection. Varied numbers of human papillomavirus infective cells were detected by RNAscope assay in different patients even though they were all human papillomavirus high-risk subtype positive discovered by human papillomavirus PCR results. A cell malignancy related long non-coding RNA, TERC, has been detected in seven patient samples. The patient follow-up information was further analyzed with RNAscope results which indicated a combination of RNAscope positive signals of TERC and human papillomavirus high risk signals in more than 10 cells (cytoplasm or nucleus) may connect with cervical lesion fast progression which deserves further studies in the future.C Conclusions Taken together, current study has provided an observable clue for gynecologists to evaluate human papillomavirus infection stage and cell malignancy status which may contribute for assessment of cervical disease progression.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Human papillomavirus E6E7 mRNA and TERC lncRNA in situ detection in cervical scraped cells and cervical disease progression assessment

Zhao

Fan

et al. 2022

Virol J

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“…Our results were consistent with the above mentioned studies, indicating that HPV load did not have prognostic significance in cervical cancer patients. However, several studies reported about the correlation between the viral load and recurrence-free survival, with p-values between 0.00 and 0.05 [34,35]. Thus, the prognostic significance of pretreatment HPV load in cervical cancer is still controversial.…”

Section: Discussionmentioning

confidence: 99%

HPV status and its genomic integration affect survival of patients with cervical cancer

Ибрагимова¹,

Цыганов²,

Shpileva³

et al. 2018

neo

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To evaluate the relapse-free and overall survival of HPV-positive patients with regard to the physical status of type 16 HPV and of HPV-negative patients with primary CC. As a main result of the study the predictive value of the physical status of type 16 HPV was determined for relapse-free and overall survival of patients with CC. Episomal form of the virus is a favorable predictive factor. Integrated form of the virus is a severely unfavorable predictive factor and survival of such patients is significantly lower, than for HPV- patients and patients with mixed form of the virus. The results of the research are data on survival of patients with CC depending on the physical status of the virus (for HPV+ patients) and of patients with HPV-negative cancer.

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“…Indeed, the results of studying the relationship between various HPV parameters and clinical outcome in patients with CC after radiation and/or chemoradiation therapy are controversial. The inconsistency in the assessment of the prognostic value refers to such HPV parameters as genotype [24][25][26][27][28], viral load (VL) [29][30][31][32][33] and the integration of HPV DNA into the cell genome [34][35][36][37]. At the same time, the presence of HPV before treatment is almost unambiguously considered as a favorable prognostic marker, and HPV-negativity is associated with an increased risk of disease progression after treatment [38,39].…”

Section: Introductionmentioning

confidence: 99%

HPV Status and Individual Characteristics of Human Papillomavirus Infection as Predictors for Clinical Outcome of Locally Advanced Cervical Cancer

Мкртчян

Замулаева

Крикунова

et al. 2021

JPM

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This study is aimed at searching for an informative predictor of the clinical outcome of cervical cancer (CC) patients. The study included 135 patients with locally advanced cervical cancer (FIGO stage II–III) associated with human papillomavirus (HPV) 16/18 types or negative status of HPV infection. Using logistic regression, we analyzed the influence of the treatment method, clinical and morphological characteristics, and the molecular genetic parameters of HPV on the disease free survival (DFS) of patients treated with radiotherapy or chemoradiotherapy. Multivariate analysis revealed three factors that have prognostic significance for DFS, i.e., HPV-related biomarker (HPV-negativity or HPV DNA integration into the cell genome) (OR = 9.67, p = 1.2 × 10−4), stage of the disease (OR = 4.69, p = 0.001) and age (OR = 0.61, p = 0.025). The predictive model has a high statistical significance (p = 5.0 × 10−8; Nagelkirk’s R2 = 0.336), as well as sensitivity (Se = 0.74) and specificity (Sp = 0.75). Thus, simultaneous accounting for the clinical and molecular genetic predictors (stage of the disease, patient age and HPV-related biomarker) makes it possible to effectively differentiate patients with prognostically favorable and unfavorable outcome of the disease.

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Prognostic significance of human papillomavirus viral load in correlation with different therapeutic modalities in cervical cancer patients

Cited by 9 publications

References 20 publications

Human papillomavirus E6E7 mRNA and TERC lncRNA in situ detection in cervical scraped cells and cervical disease progression assessment

Human papillomavirus E6E7 mRNA and TERC lncRNA in situ detection in cervical scraped cells and cervical disease progression assessment

HPV status and its genomic integration affect survival of patients with cervical cancer

HPV Status and Individual Characteristics of Human Papillomavirus Infection as Predictors for Clinical Outcome of Locally Advanced Cervical Cancer

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