Clinicopathologic and molecular markers in cervical carcinoma: a prospective cohort study

Halle, Mari K.; Ojesina, Akinyemi I.; Engerud, Hilde; Woie, Kathrine; Tangen, Ingvild L.; Holst, Frederik; Høivik, Erling A.; Kusonmano, Kanthida; Haldorsen, Ingfrid S.; Vintermyr, Olav Karsten; Trovik, Jone; Bertelsen, Bjørn; Salvesen, Helga B.; Krakstad, Camilla

doi:10.1016/j.ajog.2017.05.068

Cited by 47 publications

(54 citation statements)

References 35 publications

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“…KRAS mutations have been linked to higher rates of tumour relapse in patients with non-SCC of the cervix 11 . TP53 gene aberrations (deletion or mutations) have been reported to be associated with worse survival; CC patients with mutated TP53 had the poorest prognosis 27 . Although CTCNB1 mutations in CC patients are rare, a significant association between CC recurrence and cervical SCC has been reported 16 .…”

Section: Discussionmentioning

confidence: 99%

Clinical implication of oncogenic somatic mutations in early-stage cervical cancer with radical hysterectomy

Watanabe

Nanamiya

Kojima

et al. 2020

Sci Rep

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It is well known that tumour initiation and progression are primarily an accumulation of genetic mutations. The mutation status of a tumour may predict prognosis and enable better selection of targeted therapies. In the current study, we analysed a total of 55 surgical tumours from stage IB-IIB cervical cancer (CC) patients who had undergone radical hysterectomy including pelvic lymphadenectomy, using a cancer panel covering 50 highly mutated tumorigenesis-related genes. In 35 patients (63.6%), a total 52 mutations were detected (58.3% in squamous cell carcinoma, 73.7% in adenocarcinoma), mostly in PIK3CA (34.5%) and KRAS and TP53 (9.1%). Being mutation-positive was significantly correlated with pelvic lymph node (PLN) metastasis (P = 0.035) and tended to have a worse overall survival (P = 0.076). In particular, in the patients with squamous cell carcinoma, there was a significant association between being mutation-positive and relapse-free survival (P = 0.041). The patients with PLN metastasis had a significantly worse overall survival than those without (P = 0.006). These results indicate that somatic mutation status is a predictive biomarker for PLN metastasis in early-stage CC, and is consequently related to poor prognosis. Therefore, comprehensive genetic mutations, rather than a single genetic mutation, should be examined widely in order to identify novel genetic indicators with clinical usefulness.

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Section: Discussionmentioning

confidence: 99%

Clinical implication of oncogenic somatic mutations in early-stage cervical cancer with radical hysterectomy

Watanabe

Nanamiya

Kojima

et al. 2020

Sci Rep

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“…In developing countries, less than 50% of women affected by cervical cancer survive for more than 5 years compared to 66% in developed countries (5). This type of malignant neoplasm presents a variety of histological types, with squamous cell carcinoma accounting for up to 95% of cases, followed by adenocarcinoma and adenosquamous carcinoma (6).…”

Section: Introductionmentioning

confidence: 99%

HPV 18 Variants in Women with Cervical Cancer in Northeast Brasil

Santos¹,

Cunha²,

Batista³

et al. 2020

Preprint

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Abstract Background: Human Papillomavirus (HPV) is the main etiological factor for the development of cervical cancer. HPV 18 is the second most frequent, accounting for up to 65% of all cases. HPV intratypic variation may influence the potential for progression to invasive cancer.The aim of this study was to evaluate the prevalence of human papillomavirus 18 intratypic variants in cervical cancer samples from women in the Northeast of Maranhão. Methods: The study was composed of 118 women over 18 years of age with a diagnosis of cervical cancer. Tumor fragments were collected and subjected to DNA extraction and Polymerase Chain Reaction (PCR) for HPV detection using the PGMY09/11 and GP+5/6 primers. Positive samples were submitted to automated sequencing for viral genotyping. To determine the HPV 18 lineages, positive samples were submitted to PCR, using specific primers to amplify the LCR and E6 regions of HPV 18 virus. Results: HPV was present in 88 women (73.3%), and HPV 16 was the most prevalent (48/54%), followed by HPV 18 (12/13.6%). Histologically, squamous cell carcinoma was predominant (79.1%). Among the HPV 18 variants identified, 10 (80%) belonged to lineage A, and sublineages A1, A2, A3, and A4. HPV 18 B variant (2/29%) was also detected, with the sublineages B1 and B2. In this study, the C variant was not found. There was no statistically significant association between the HPV 18 lineages found and sociodemographic and lifestyle variables (p > 0.05). Conclusions: Women with cervical cancer are associated with a higher frequency of HPV 16 and 18 in the Northeast region of Brazil, with a high prevalence of the lineage A among women with HPV 18.

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“…Absence of p53 is significantly associated with tumors <4 cm, adenocarcinoma and deep invasion. (10) . Histological distribution of Ki-67 is modified, with HPV infection being associated to high-risk HPV infection (16) .…”

Section: Cenário Atual Dos Biomarcadores No Câncer Cervical E Na Oncomentioning

confidence: 99%

“…of the transformation zone (LLETZ), loop electrosurgical excision procedure (LEEP) to cold-knife conization (CKC), and sometimes other treatment modalities, as laser or cryosurgery. Incidence among young women has expressive rates, and treatment can relate to severe consequences in the reproductive function, such as fetal consequences of low birth weight, premature birth, and miscarriage (9,10) .…”

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J Bras Doenças Sex Transm

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Cervical cancer (CC) is related to HPV infection and represents the third cause of cancer in women. Annually, more than 500,000 new cases are reported worldwide, with significant death rates. It develops due to genetic and epigenetic alterations that control cell growth and differentiation, and may cause death. These alterations induce uncontrolled cell division and invasion of cervical tissue have severe consequences to women's health (1). CC incidence and mortality drop considerably since the implementation of screening tests and vaccination strategies. Nevertheless, CC continues to have a high incidence, mainly in low-income countries, where these programs do not cover territorial frontiers and there is lack of resources to implement vaccination or screening tests. Oncogenic HPV types reached 25% of cases in Brazil over the last years (2) , and there was no modification on HPV types after four years of the vaccination program, according to Tota et al. (3). Usually, screening tests in Brazil cover women from 25 to 64 years old. According to Teixeira et al. (4) , rates of CC under the age of 25 tend to increase, and women over 64 achieved roughly 20% of CC on research of Brazilian women from two high-income cities. HPV 16 and 18 are the predominant genotypes linked to progression to invasive cancer. HPV uses evasion mechanisms of the immune system in early and late stages of the infection, causing its persistence in cutaneous and mucosal tissues. Its continuous expression of viral proteins E6 and E7 contribute to disease progression (5). Starting lesions are well defined and classified into cervical intraepithelial neoplasm 1, 2, and 3, with grade 3 being the highest level of evolution. Factors such as age, smoking, sexually transmitted disease, long-term oral contraceptive use, and parity are associated to a higher risk of cervical cancer development (6,7). Many CIN 1, 2, and some CIN 3 lesions spontaneously revert. Even though, treatment is still needed, because they have high chances to progress (8) .

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Clinicopathologic and molecular markers in cervical carcinoma: a prospective cohort study

Cited by 47 publications

References 35 publications

Clinical implication of oncogenic somatic mutations in early-stage cervical cancer with radical hysterectomy

Clinical implication of oncogenic somatic mutations in early-stage cervical cancer with radical hysterectomy

HPV 18 Variants in Women with Cervical Cancer in Northeast Brasil

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