Dataset Information

Spatiotemporally deciphering the mysterious mechanism of persistent HPV-induced malignant transition and immune remodelling from HPV-infected normal cervix, precancer to cervical cancer: Integrating single-cell RNA-sequencing and spatial transcriptome.

ABSTRACT:

Background

The mechanism underlying cervical carcinogenesis that is mediated by persistent human papillomavirus (HPV) infection remains elusive.

Aims

Here, for the first time, we deciphered both the temporal transition and spatial distribution of cellular subsets during disease progression from normal cervix tissues to precursor lesions to cervical cancer.

Materials & methods

We generated scRNA-seq profiles and spatial transcriptomics data from nine patient samples, including two HPV-negative normal, two HPV-positive normal, two HPV-positive HSIL and three HPV-positive cancer samples.

Results

We not only identified three 'HPV-related epithelial clusters' that are unique to normal, high-grade squamous intraepithelial lesions (HSIL) and cervical cancer tissues but also discovered node genes that potentially regulate disease progression. Moreover, we observed the gradual transition of multiple immune cells that exhibited positive immune responses, followed by dysregulation and exhaustion, and ultimately established an immune-suppressive microenvironment during the malignant program. In addition, analysis of cellular interactions further verified that a 'homeostasis-balance-malignancy' change occurred within the cervical microenvironment during disease progression.

Discussion

We for the first time presented a spatiotemporal atlas that systematically described the cellular heterogeneity and spatial map along the four developmental steps of HPV-related cervical oncogenesis, including normal, HPV-positive normal, HSIL and cancer. We identified three unique HPV-related clusters, discovered critical node genes that determined the cell fate and uncovered the immune remodeling during disease escalation.

Conclusion

Together, these findings provided novel possibilities for accurate diagnosis, precise treatment and prognosis evaluation of patients with precancer and cervical cancer.

SUBMITTER: Guo C

PROVIDER: S-EPMC10040725 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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Publications

Spatiotemporally deciphering the mysterious mechanism of persistent HPV-induced malignant transition and immune remodelling from HPV-infected normal cervix, precancer to cervical cancer: Integrating single-cell RNA-sequencing and spatial transcriptome.

Guo Chenyan C Qu Xinyu X Tang Xiaoyan X Song Yu Y Wang Jue J Hua Keqin K Hua Keqin K Qiu Junjun J

Clinical and translational medicine 20230301 3

<h4>Background</h4>The mechanism underlying cervical carcinogenesis that is mediated by persistent human papillomavirus (HPV) infection remains elusive.<h4>Aims</h4>Here, for the first time, we deciphered both the temporal transition and spatial distribution of cellular subsets during disease progression from normal cervix tissues to precursor lesions to cervical cancer.<h4>Materials & methods</h4>We generated scRNA-seq profiles and spatial transcriptomics data from nine patient samples, includi ...[more]

PMID: 36967539

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Project description:The oral transmission of HPV and, consequently, the risk of oral cancer has increased in the last years. Oral sex has often been implicated among the risk factors for oral HPV infections, however, there is still no consensus on these topics, nor on the relationship between genital and oral HPV infections. The present study aimed to evaluate the coexistence of papilloma virus, at the levels of the oral and genital mucosa, in women with a histologically confirmed HPV lesions (and a positive HPV test) at the genital level and a negative HPV control group. We also evaluated how some risk factors, such as smoking, the number of partners, age, and sexual habits can influence the possible presence of the virus itself in the oropharynx of the same women. In total, 117 unvaccinated women aged between 18 and 52 were enrolled. We found that the prevalence of oral HPV infection was high among the women with concomitant genital HPV infection (22%) compared to the HPV-negative women (0%), and the estimated odds ratio was 17.36 (95% CI: 1.02, 297.04). In none of the women with oral HPV did we find any relevant clinical lesions. The potential risk factors for HPV infections in the oropharynx and genitals were analyzed based on questionnaire responses. A multivariate analysis showed that genital HPV infections were significantly associated with a number of sexual partners > 10 (OR 138.60, 95% CI: 6.04-3181.30, p < 0.001), but the data also referred to having between 3-5 or 6-10 partners as being significant, as were a high level of education (OR 6.24, 95% CI: 1.67-4.23.26 p = 0.003), a frequency of sexual intercourse >10 (OR 91.67 95% CI: 3.20-2623.52, p = 0.004), oral sex (OR 6.16, 95% CI: 1.22-31.19, p = 0.014), and >20 cigarettes/day (OR 6.09 95% CI: 1.21-30.61, p = 0.014). Furthermore, being "separate" and having multiple sexually transmitted diseases were also significantly associated with genital HPV infection. In contrast, oral HPV infections were significantly associated with women aged 36 to 50 years (OR 27.38, 95% CI: 4.37-171.37; p = 0.000202) and oral sex (OR 95.5, 95% CI: 5.13-1782.75, p = 0.001126).Additionally, being separate, being cohabitant, lifetime sexual partners of >10, 3-5 lifetime sexual partners, <20 years of age, >10 sexual intercourse per month, occasional and regular anal sex, >20 cigarettes per day, a history of sexually transmitted disease (herpes and multiple), and having a history of genital warts were significant. Screening and early diagnosis are considered to be practically unfeasible for this category of cancer, given the lack of visible lesions; the 9-valent HPV vaccine remains the only means that could help to successfully counter the growing incidence of oral squamous cell carcinoma.

Project description:A dramatic increase in cervical diseases associated with human papillomaviruses (HPV) in women of reproductive age has been observed over the past decades. An accurate differential diagnosis of the severity of cervical intraepithelial neoplasia and the choice of the optimal treatment requires the search for effective biomarkers with high diagnostic and prognostic value. The objective of this study was to introduce a method for rapid shotgun lipidomics to differentiate stages of HPV-associated cervix epithelium transformation. Tissue samples from 110 HPV-positive women with cervicitis (n = 30), low-grade squamous intraepithelial lesions (LSIL) (n = 30), high-grade squamous intraepithelial lesions (HSIL) (n = 30), and cervical cancers (n = 20) were obtained. The cervical epithelial tissue lipidome at different stages of cervix neoplastic transformation was studied by a shotgun label-free approach. It is based on electrospray ionization mass spectrometry (ESI-MS) data of a tissue extract. Lipidomic data were processed by the orthogonal projections to latent structures discriminant analysis (OPLS-DA) to build statistical models, differentiating stages of cervix transformation. Significant differences in the lipid profile between the lesion and surrounding tissues were revealed in chronic cervicitis, LSIL, HSIL, and cervical cancer. The lipids specific for HPV-induced cervical transformation mainly belong to glycerophospholipids: phosphatidylcholines, and phosphatidylethanolamines. The developed diagnostic OPLS-DA models were based on 23 marker lipids. More than 90% of these marker lipids positively correlated with the degree of cervix transformation. The algorithm was developed for the management of patients with HPV-associated diseases of the cervix, based on the panel of 23 lipids as a result. ESI-MS analysis of a lipid extract by direct injection through a loop, takes about 25 min (including preparation of the lipid extract), which is significantly less than the time required for the HPV test (several hours for hybrid capture and about an hour for PCR). This makes lipid mass spectrometric analysis a promising method for express diagnostics of HPV-associated neoplastic diseases of the cervix.

Dataset Information

Spatiotemporally deciphering the mysterious mechanism of persistent HPV-induced malignant transition and immune remodelling from HPV-infected normal cervix, precancer to cervical cancer: Integrating single-cell RNA-sequencing and spatial transcriptome.

Background

Aims

Materials & methods

Results

Discussion

Conclusion

Publications

Spatiotemporally deciphering the mysterious mechanism of persistent HPV-induced malignant transition and immune remodelling from HPV-infected normal cervix, precancer to cervical cancer: Integrating single-cell RNA-sequencing and spatial transcriptome.

Similar Datasets

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