Molecular Pathology of Human Papilloma Virus-Negative Cervical Cancers

Yoshida, Hiroshi; Shiraishi, Kouya; Kato, Tomoyasu

doi:10.3390/cancers13246351

Cited by 24 publications

(32 citation statements)

References 149 publications

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“…Despite well-recognized differences between the pathology [ 12 , 13 ] and clinical outcomes [ 8 , 9 , 10 , 11 ] between HPV-positive and HPV-negative CC, few if any studies have directly compared the tumor immune microenvironment between these distinct cancers of the cervix. Cancer is a complex disease, and it has become increasingly clear that patient outcomes depend greatly on crosstalk between the tumor and its local immune microenvironment [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

“…HPV18 and 45 are members of the α7 family, which includes closely related types HPV39, 59, 68, 70, 85, and 97 [ 6 ]. Patients with HPV-positive CC appear to have a more favorable prognosis than their HPV-negative counterparts [ 8 , 9 , 10 , 11 ], and it is clear that HPV-positive and HPV-negative diseases are clinically and pathologically distinct [ 12 , 13 ]. Although somewhat controversial, patient outcomes for HPV16-positive CC appear superior to those that are HPV18-positive [ 10 , 14 , 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

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HPV-Positive and -Negative Cervical Cancers Are Immunologically Distinct

Evans

Salnikov

Gameiro

et al. 2022

JCM

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Although infection with human papillomavirus (HPV) is associated with nearly all cervical cancers (CC), a small proportion are HPV-negative. Recently, it has become clear that HPV-negative CC represent a distinct disease phenotype compared to HPV-positive disease and exhibit increased mortality. In addition, variations between different HPV types associated with CC have been linked to altered molecular pathology and prognosis. We compared the immune microenvironments of CC caused by HPV α9 species (HPV16-like), HPV α7 species (HPV18-like) and HPV-negative disease. HPV-negative CC appeared distinct from other subtypes, with greatly reduced levels of lymphocyte infiltration compared to either HPV α9 or α7 CC. Besides reduced levels of markers indicative of B, T, and NK lymphocytes, the expression of T-cell effector molecules, activation/exhaustion markers, and T-cell receptor diversity were also significantly lower in HPV-negative CC. Interestingly, HPV-negative CC expressed much higher levels of potential neoantigens than HPV-positive CC. These results identify profound differences between the immune landscape of HPV-positive and HPV-negative CC as well as modest differences between HPV α9 and α7 CC. These differences may contribute to altered patient outcomes between HPV-negative and HPV-positive CC and potentially between CC associated with different HPV types.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

HPV-Positive and -Negative Cervical Cancers Are Immunologically Distinct

Evans

Salnikov

Gameiro

et al. 2022

JCM

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“…HPV-negative CCs are diagnosed statistically later than HPV-positive CCs and correlate with shorter survival. Apart from the diagnostic delay, molecular correlations have not been demonstrated to date [ 26 ].…”

Section: Review Resultsmentioning

confidence: 99%

Cervical Cancer Prophylaxis—State-of-the-Art and Perspectives

Poniewierza¹,

Panek

2022

Healthcare

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Background: Each year 604,127 new cases of cervical cancer (CC) are diagnosed, and 341,831 individuals die from the disease. It is the fourth most common cancer among women and the fourth most common cause of death from female cancers worldwide. The pathogenesis of CC is associated with human papillomavirus (HPV) infections and consists of several steps involving cell proliferation outside the human body’s control mechanisms. Strategies to prevent CC are based on screening and vaccination. Scope of the Review: The aim of this paper was to collect and analyze the available literature on the issue of CC prevention and the impact of the COVID-19 pandemic on its implementation. For this purpose, PubMed and Google Scholar databases were searched using keywords, such as “cervical cancer”; “HPV”; “prevention”; “prophylaxis”; “vaccination”; “screening” and “COVID-19” in different variations. Only articles published since 2018 were included in the study. Conclusions: Selected European countries have different CC prevention programs funded by national budgets. This translates into observed differences in the risk of death from CC (age-standardized rate Malta = 1.1, Poland = 5.9). COVID-19 pandemic due to disruption of CC screening may exacerbate these differences in the future. To improve the situation, new screening methods, such as p16/Ki67, HPV self-testing, and the use of artificial intelligence in colposcopic assessment, should be disseminated, as well as free HPV vaccination programs implemented in all countries. The search for new solutions is not without significance and entails ultra-sensitive screening tests for risk groups (mRNA E6/E7, SOX1/SOX14), HPV vaccines with shorter dosing schedules, and new therapeutic pathways using nanotheranostics.

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“…Malignant tumors of the female reproductive tract are most prevalent in developing countries [15]. Although the widespread application of cervical cytology screening in the past decade has led to a decline in the incidence and mortality of cervical cancer in Chinese women, there is still a lack of standardized and systematic cervical cancer prevention programs.…”

Section: Discussionmentioning

confidence: 99%

“…It may be related to decreased body immunity and the reactivation of menopausal latent HPV [28,29]. Women in this group are more likely to show persistent HPV infection [15,30] and have a higher risk of cervical cancer. Therefore, it is necessary to strengthen comprehensive and regular cervical screening for HPV-positive middle-aged and older women [12,30,31].…”

Section: Discussionmentioning

confidence: 99%

Epidemiological study of HPV infection in 40693 women in Putian: a population study based on screening for high-risk HPV infection

Chen

Lin

Zheng

et al. 2022

Preprint

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Background: The infection rate of human papillomavirus (HPV) is high in coastal regions of China. However, the infection of high-risk genotypes of women in Putian City is unknown. Therefore, this study aimed to analyse the epidemiology of high-risk HPV infection among women in Putian and provide a reference for the diagnosis, treatment, and vaccination of cervical cancer in this region.Methods: A total of 40693 female cervical cell exfoliation samples screened for high-risk HPV at the Affiliated Hospital of Putian University from July 2020 to December 2021 were selected. DNA was extracted using a fully automatic extractor. Then, 14 high-risk genotypes of HPV were detected by polymerase chain reaction. The characteristics of HPV infection, distribution of high-risk genotypes, infection types, and TCT classification in different age groups were analysed.Results: Of the 40693 samples, 3899 were infected with HPV, with an infection rate of 9.6%. Accordingly, HPV infection rates gradually increased with age, with statistically significant differences among age groups (χ2=74.03, P<0.01). The infection rates of high-risk HPV52, HPV58, and HPV16 ranked in the top three and increased with age. Single infection was dominant (84.7%), followed by double infections (12.7%). In addition, the cervical cytological classification of 3899 HPV-positive people was as follows: NILM (88.0%), ASC-US (6.6%), ASC-H (1.4%), LSIL (3.2%), and HSIL (0.8%). The study found that the HPV16 infection rate increased with increasing severity of cervical cytology (χ2trend=43.64, P<0.01), while the infection rates of HPV52 (χ2trend=13.89, P<0.01) and HPV58 (χ2trend=13.50, P<0.01) showed opposite trends.Conclusions: The infection rate of female HPV high-risk screening in this region was 9.6%, mainly for single infections. In addition, HPV16, HPV52, and HPV58 were closely related to the severity of cervical cytology. When vaccinated against HPV, the nine-valent vaccine is more effective in preventing infection. Health departments and medical institutions need to strengthen regular HPV screening and science publicity for young and middle-aged women, since both are crucial for preventing cervical cancer.

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Molecular Pathology of Human Papilloma Virus-Negative Cervical Cancers

Cited by 24 publications

References 149 publications

HPV-Positive and -Negative Cervical Cancers Are Immunologically Distinct

HPV-Positive and -Negative Cervical Cancers Are Immunologically Distinct

Cervical Cancer Prophylaxis—State-of-the-Art and Perspectives

Epidemiological study of HPV infection in 40693 women in Putian: a population study based on screening for high-risk HPV infection

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