Infectious Agents and Cancer最新文献

Infectious Agents and Cancer (2023) 18:54

https://doi.org/10.1186/s13027-023-00531-w

After publication of this article [1], the authors reported that in this article all authors were assigned to affiliations 1 and 2, but it should be as follows:

Ying Liu: 1 and 2;

Xiu Jin, Yingying Gong, Yingying Ma, Beibei Du, Linqing Yang and Yunfei Wang: 2;

Weipei Zhu: 1.

The original article [1] has been corrected.

1. Liu Y, Jin X, Gong Y, et al. Do women with high-risk HPV E6/E7 mRNA test positivity and NILM cytology need colposcopy? Infect Agents Cancer. 2023;18:54. https://doi.org/10.1186/s13027-023-00531-w.

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Authors and Affiliations

1. Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Soochow University, Suzhou, 215000, China

   Ying Liu & Weipei Zhu

2. Department of Gynecology, Affiliated Hospital of Jining Medical University, Shandong, 272000, China

   Ying Liu, Xiu Jin, Yingying Gong, Yingying Ma, Beibei Du, Linqing Yang & Yunfei Wang

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2. Xiu JinView author publications

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3. Yingying GongView author publications

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6. Linqing YangView author publications

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The online version of the original article can be found at https://doi.org/10.1186/s13027-023-00531-w

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The era of precision medicine requires the achievement of accurate risk assessment. Polygenic risk scores (PRSs) have strong potential for increasing the benefits of nationwide cancer screening programs. The current pool of evidence on the role of a PRS as a risk stratification model in actual practice and implementation is limited. To better understand the impact of possible method-induced variance, we constructed and validated two PRSs for cervical cancer (CC) using the Estonian Biobank female population (691 CC cases and 13,820 controls) and evaluated their utility in predicting incident cervical neoplasia (CIN), cancer, and human papillomavirus (HPV) infection using two methods (LDPred and BayesRR-RC). This study demonstrated that two genetic risk scores were significantly associated with CIN, CC, and HPV infection incidence. Independent of the method, we demonstrated that women with elevated PRS values reached the observed cumulative risk levels of CIN or CC much earlier. Our results indicated that the PRS-based discrimination rules could differ substantially when the PRSs contain similar predictive information. In summary, our analysis indicated that PRSs represent a personalized genetic component that could be an additional tool for cervical cancer risk stratification, and earlier detection of abnormalities provides invaluable information for those at high risk.

Background: Cervical cancer is preventable through screening and vaccination against high-risk human papillomavirus (hr-HPV). For a screening program to be successful it is vital that the clinical management and follow-up regime of patients with abnormal screening results is well developed and that the attendance rate for follow-up is high. The aim of the study was to analyze how effective conization with recommended follow-up was in preventing subsequent cervical cancer, and to evaluate how clinical follow-up recommendations are obeyed in the region of Skåne, Sweden.

Methods: All women (n = 8835) who had undergone conization in the region of Skåne, Sweden, between the years of 2015 and 2021 were identified. Individuals with confirmed cervical cancer in the conization material were referred for additional treatment (n = 114), leaving 8721 included in the follow-up. Adherence to follow-up and cytological, histopathological and HPV status at follow-up were collected at eight, 12 and 24 months post-conization. The total follow-up time was from January 1, 2015, to January 30, 2023.

Results: Within 12 months post-conization, 90% of the patients conducted a cytological cervical sample. The rates of a negative test of cure (HPV negative and normal cytology) were 69.7%, 76.3% and 84.4% at eight, 12 and 24 months post-conization respectively. The clearance of HPV was 79.6%, 80.8% and 87.8% at eight, 12 and 24 months post-conization respectively. Out of 5613 patients with a negative test of cure within one year after conization, no cervical cancer was found during follow-up and 11 (0.2%) women developed high-grade intraepithelial lesions/adenocarcinoma in situ (HSIL/AIS) with an average time from conization to new diagnosis of 42 months. The mean follow-up time was 32.1 months.

Conclusions: The clearance rate of hr-HPV post cervical conization due to dysplasia appears to be high within eight months. With a negative test of cure post cervical conization, the risk of cervical cancer within the following three years seems to be extremely low and the risk of developing HSIL/AIS was lower than the incidence of HSIL/AIS in the general screening population.

Background: Despite the introduction of combined antiretroviral therapy, the clinical outcomes of HIV-associated Burkitt lymphoma (BL) remain poor.

Methods: To evaluate the clinical characteristics, prognostic factors, and outcomes of HIV-associated BL, we conducted a retrospective analysis of patients from multiple centers in China.

Results: The study included 41 patients from 8 medical centers. Among the included population, male patients accounted for 87.8%, with 75.6% in advanced stages. Notably, 46.3% of cases involved bone marrow, while 19.5% involved the central nervous system (CNS). The most commonly used chemotherapy regimen was DA-EPOCH ± R, accounting for 53.6% of cases. The overall response rates for patients receiving DA-EPOCH ± R and R-Hyper-CVAD were 59% and 58.2%, respectively. Interestingly, patients receiving regimens containing rituximab had similar complete remission rates (25% vs. 23.5%) and overall survival time (45.69 ± 11.58 vs. 47.79 ± 11.72 months, P = 0.907) compared to those without rituximab, but differed in progression rates (33.3% vs. 47.1%). For the entire cohort, the 1-year progression-free survival (PFS) and overall survival (OS) rates were 52% and 67%, respectively. CNS involvement was independent risk factors for survival, with 1-year PFS and OS rates of 0% and 38% for patients with CNS involvement, and PFS and OS rates of 66% and 75% for patients without CNS involvement.

Conclusions: HIV-associated BL patients in China have poor prognosis and show limited response to current treatment regimens. The absence of CNS involvement significantly improves clinical outcomes. The use of rituximab is not significantly associated with improved outcomes but can reduce disease progression.

Background: The role of high-risk human papillomaviruses (hr-HPVs) in cervical cancer (CC) pathogenesis has long been established. Knowledge about the involvement of hr-HPVs in the etiology of nasopharyngeal cancers (NPC) was not well appreciated until the early 2000s when a clear link began to emerge. However, it is not clear whether HPV oncogenesis in the different epithelial cancers is associated with L1 gene and long-control region (LCR) sequences variation. This study aimed to investigate the HPV18 L1 gene and LCR sequences variation in cervical and nasopharyngeal biopsies, and assessed E6 and E7 genes expression level in both cancers.

Method: Four-hundred and three (403) formalin-fixed paraffin-embedded tissues originating from nasopharyngeal (NPC) (279) and cervical (CC) (124) sites were collected from a pathology laboratory, Pathologist Without Borders, Accra, Ghana. Haematoxylin and eosin staining was carried out to confirm the presence of cancer on prepared biopsy sections. DNA was extracted from the confirmed cancer biopsies, followed by PCR using MY09/GP5+ /6+ primers to detect the presence of HPV and specific primers for the amplification of L1 gene and LCR. Sanger sequencing was carried out to determine HPV genotypes, and L1 and LCR sequences variant of HPV18s in CC and NPC biopsies. The HPV18 E6/E7 mRNA expression pattern in both cancers was determined using RT-qPCR.

Results: Most of the NPC (45%) and CC (55%) biopsies were HPV18 positive. Comparison of HPV18 L1 sequences obtained from cervical and nasopharyngeal cancer tissues, the L1 sequences from the NPC were highly dissimilar with a 59-100% variation among themselves, and in relation to the reference strains. However, the L1 sequences from the CC were more similar with a 91.0-100% variation among the amplified sequences. Also, the LCR sequences from CC were quite different relative to that of NPC. Results for the differential expression of E6/E7 in the two cancers showed a higher fold change in E6 expression in the CC tissues than the NPC tissues while a reverse expression pattern was found for E7 gene.

Conclusion: The current study reports for the first-time variations in HPV18 L1 and LCR sequences, and differential expression of E6/E7 genes in NPC compared to CC, suggesting a possible adaptation mechanism of the virus at different cancer sites.

Objectives: The aim of this study was to determine the prevalence of Chlamydia trachomatis (CT) and Mycoplasma genitalium (MG) among HPV-positive women undergoing colposcopy at the Second Xiangya Hospital of Central South University, Hunan, China. Additionally, we aimed to assess the impact of C. trachomatis or M. genitalium co-infection with HPV on the severity of cervical lesions.

Methods: We collected HPV data, cervical cytology results, and demographic information from 439 women attending colposcopy. Cervical swabs were obtained for simultaneous amplification testing (SAT) of C. trachomatis and M. genitalium. Multivariate logistic regression analyses were performed to examine the association between sexually transmitted pathogens and cervical lesions.

Results: Among the participants, C. trachomatis was detected in 17 (3.87%) individuals, and M. genitalium in 16 (3.64%) individuals. There was no co-infection of C. trachomatis and M. genitalium. The highest prevalence of M. genitalium was observed in women aged 19-30 years (10.20%; 95% CI, 1.41-18.99%), with a subsequent decline in prevalence with increasing age (Ptrend = 0.014). The most common HPV subtype in our study was HPV52 (30.79%), followed by HPV16 (18.62%), HPV58 (16.95%), and HPV53 (10.02%). Infection with HPV16 (OR = 3.43, 95% CI, 2.13-5.53), HPV31 (OR = 3.70, 95% CI, 1.44-9.50), and HPV33 (OR = 3.71, 95% CI, 1.43-9.67) was associated with an increased severity of cervical lesions, while HPV53 infection was not likely to lead to advanced cervical lesions (OR = 0.45, 95% CI, 0.23-0.89). The leukocyte level in vaginal secretions (P = 0.042) and cervical cytology results (P < 0.001) showed associations with the degree of cervical lesions. However, there was no significant association between C. trachomatis or M. genitalium infection and the severity of cervical lesions, nor with their co-infection with HPV16.

Conclusions: There was no correlation between co-infection of Chlamydia trachomatis or Mycoplasma genitalium and the degree of cervical lesions in HPV-positive population in Hunan, China. Our findings emphasized the need to pay more attention to M. genitalium infection among young women. Increased levels of leukocytes in vaginal secretions may be linked to cervical lesions. HPV16, HPV31, and HPV33 in Hunan province, China, may exhibit higher cervical pathogenicity.

It is commonly accepted that host genes show high methylation in cervical intraepithelial neoplasia 3 (CIN3) or worse (CIN3+). However, study quality varies, as does the clinical performance of markers in different populations. We aimed to validate candidate gene DNA methylation with standardized testing methods in the same batch of samples. We first compared the performance of 16 DNA methylation markers for detecting CIN3+ in the 82-sample training set, including 24 subjects with ≤ CIN1, 10 subjects with CIN2, 23 subjects with CIN3, and 25 subjects with cervical cancer (CC). Then five methylation markers were selected and subsequently validated among an independent set of 74 subjects, including 47 subjects with ≤ CIN1, 13 subjects with CIN2, 6 subjects with CIN3, and 8 subjects with CC. The results in the validation set revealed that methylation analysis of the SOX1 (SOX1^m) showed a superior level of clinical performance (AUC = 0.879; sensitivity = 85.7%; specificity = 90.0%). SOX1^m had better accuracy than cytology, with a reduced referral rate (23.0% vs. 31.4%) and a lower number of overtreatment (5 vs. 13) cases among high-risk human papillomavirus (hrHPV)-positive women. Importantly, among hrHPV-positive and SOX1^m-negative women, only 1 CIN3 patient was at risk for follow-up after 1 year, whereas 1 CIN3 patient and 1 CC patient were at risk among hrHPV-positive and cytology-negative women. In this investigation, we screened 16 reported methylation markers to provide a basis for future studies related to potential precancerous lesion/cancer methylation markers in the Chinese population. The study also revealed that SOX1^m has optimal CIN3+ detection performance, suggesting that it may be a promising biomarker for detecting CIN3+ in the Chinese population.

Laryngeal cancer ranks as the second most prevalent upper airway malignancy, following Lung cancer. Although some progress has been made in managing laryngeal cancer, the 5-year survival rate is disappointing. The gradual increase in the incidence of second primary tumors (SPTs) plays a crucial role in determining survival outcomes during long-term follow-up, and the esophagus was the most common site with a worse prognosis. In clinical practice, the treatment of esophageal second primary tumors (ESPT) in patients with laryngeal squamous cell carcinoma (LSCC) has always been challenging. For patients with synchronous tumors, several treatment modalities, such as radiotherapy, chemotherapy and potentially curative surgery are necessary but are typically poorly tolerated. Secondary cancer therapy options for metachronous patients are always constrained by index cancer treatment indications. Therefore, understanding the clonal origin of the second primary tumor may be an important issue in the treatment of patients. LSCC cells demonstrate genetic instability because of two distinct aetiologies (human papillomavirus (HPV)-negative and HPV-positive) disease. Various etiologies exhibit distinct oncogenic mechanisms, which subsequently impact the tissue microenvironment. The condition of the tissue microenvironment plays a crucial role in determining the destiny and clonal makeup of mutant cells during the initial stages of tumorigenesis. This review focuses on the genetic advances of LSCC, the current research status of SPT, and the influence of key carcinogenesis of HPV-positive and HPV-negative LSCC on clonal evolution of ESPT cells. The objective is to gain a comprehensive understanding of the molecular basis underlying the clonal origins of SPT, thereby offering novel perspectives for future investigations in this field.

Background: In addition to the conventional aetiologic agents of oropharyngeal squamous cell carcinoma (OPSCC) such as tobacco usage, alcohol consumption and betel quid usage, it has been established that a proportion of OPSCC are driven by persistent oncogenic human papillomavirus (HPV) infections. Currently, there is a lack of data on the burden of HPV- associated OPSCC in Asian countries including Malaysia.

Methods: A cross-sectional multicentre study with tissue analysis of Malaysian patients diagnosed with primary OPSCC within a five-year period, from 2015 to 2019 between 01/01/2015 to 31/12/2019 was undertaken. Determination of HPV status was carried out using p16INK4a immunohistochemistry on tissue microarrays constructed from archived formalin-fixed paraffin-embedded tissue.

Results: From the cases identified, 184 cases had sufficient tissue material for analysis. Overall, median age at diagnosis was 63.0 years (IQR = 15) and 76.1% of patients were males. In our cohort, 35.3% of patients were Indian, 34.2% were Chinese, 21.2% were Malay and 9.2% were from other ethnicities. The estimated prevalence of HPV-associated OPSCC in our cohort was 31.0% (CI 24.4-38.2%). The median age for the HPV-associated OPSCC sub-group of patients was not significantly lower than the median age of patients with HPV-independent OPSCC. More than half of HPV-associated OPSCC was seen in patients of Chinese ethnicity (54.4%). Patients with HPV-associated OPSCC had a much better overall survival than patients with HPV-independent OPSCC (Log rank test; p < 0.001). Patients with HPV-associated OPSCC with no habit-related risk factors such as smoking, were found to have much better overall survival when compared to all other sub-groups.

Conclusions: The findings from our study suggests that prevalence of HPV-associated OPSCC in Malaysia, though not as high as some developed countries, is however on an upward trend. HPV-associated OPSCC appears to be more frequently encountered in patients of Chinese ethnicity. Conventional risk-factors associated with OPSCC such as smoking, alcohol consumption and betel quid chewing should still be considered when estimating prognosis of patients with HPV-associated OPSCC.