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BACKGROUND: HPV is strongly related to cervical cancer. HPV lineages can contribute to a response to cervical cancer therapy. The aim of this research was to estimate the frequency of human papillomavirus (HPV)-16 lineages in specimens of cervical cancer, relate the pathological factors in these variants, and assess their response to treatment with radical chemoradiotherapy. METHODS: Samples of cervical cancer were collected from women who were referred to a reference cancer hospital to test the presence of human papillomavirus-type DNA. The standard protocol of this service consisted of cisplatin-based chemotherapy of 40 mg/m2, plus conventional pelvic irradiation in doses of 45-50.4 Gy and high dose-rate brachytherapy of 28-30 Gy to Point A. The response to chemotherapy was evaluated after three months in patients with the HPV-16 lineage. RESULTS: HPV DNA was detected in 104 (88.1%) of the 118 patients. HPV-16 was present in 63 patients (53%). Lineages of HPV-16 were identified in 57 patients and comprised 33 instances of (57.8%) lineage A, 2 instances of lineage B (3.5%), 2 instances of lineage C (3.5%), and 20 instances of (35.0%) lineage D. The median age of the patients was 48.4 years (range 25-85 years). Squamous cell carcinoma was detected 48 times (84.2%). Adenocarcinoma was more likely to occur in lineage D, as three of the four cases occurred in this lineage. A total of 11 patients with the HPV-16 variant were treated with chemoradiotherapy. After three months, it was observed that nine of the eleven patients (81.8%) achieved a complete response, five with the lineage A type, two with the lineage C type, and two with the lineage D type. The two cases of partial response and disease progression, one of each, occurred in lineage A. CONCLUSIONS: In addition to the small number of patients and HPV variants, we noticed a better response in patients with the HPV-16 lineage A. Increasing the sample size could be helpful to better assess the impact of HPV variants on cervical cancer treatment.
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Metabolic reprogramming is considered one of the hallmarks in cancer and is characterized by increased glycolysis and lactate production, even in the presence of oxygen, which leads the cancer cells to a process called "aerobic glycolysis" or "Warburg effect". The E6 and E7 oncoproteins of human papillomavirus 16 (HPV 16) favor the Warburg effect through their interaction with a molecule that regulates cellular metabolism, such as p53, retinoblastoma protein (pRb), c-Myc, and hypoxia inducible factor 1α (HIF-1α). Besides, the impact of the E6 and E7 variants of HPV 16 on metabolic reprogramming through proteins such as HIF-1α may be related to their oncogenicity by favoring cellular metabolism modifications to satisfy the energy demands necessary for viral persistence and cancer development. This review will discuss the role of HPV 16 E6 and E7 variants in metabolic reprogramming and their contribution to developing and preserving the malignant phenotype of cancers associated with HPV 16 infection.
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PURPOSE: Although the large impact of Human papilloma virus (HPV) in cervical cancer is established, its place as a therapeutic target is new and according to the growing literature, could be promising. In the present study, radiosensitivity's difference based on HPV-16 variants is assessed. PATIENTS AND METHODS: Variants of Human papilloma virus were identified before the exclusive radiotherapy in patients with cervical cancer. Data were prospectively collected. Fifty-nine patients were screened. RESULTS: Among the 59 screened patients, 34 (57.6%) were identified to be HPV-16 (+), with 13 European and two non-European variants. Of the 34 patients, 15 experienced exclusive radiotherapy. Among them, eight had complete response (seven with European and one with non-European variants), four with European variant had partial response, three with European variant had tumour persistence and one with non-European variant progressed at 3 months. CONCLUSION: No radiosensitivity difference was established, probably because of the limited population. Non-European variant aggressiveness might be suggested in accordance with the literature, as it was associated with the only tumour progression. Exclusive radiotherapy provides a unique and "pure" model of radioresistance in cervical cancer and could be the missing link between in vitro studies and state of the art chemoradiotherapy studies that probably feature too many parameters to identify radioresistance causes. The present study was a first step, with the future prospects of building a larger cohort study in order to better understand HPV-induced radioresistance and then to be able to propose new made-to-measure treatments.
Assuntos
Papillomavirus Humano 16 , Infecções por Papillomavirus/radioterapia , Neoplasias do Colo do Útero/radioterapia , Neoplasias do Colo do Útero/virologia , Adulto , Idoso , Feminino , Variação Genética , Papillomavirus Humano 16/classificação , Papillomavirus Humano 16/genética , Humanos , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Resultado do TratamentoRESUMO
Human Papillomavirus (HPV) is the most common sexually transmitted infection worldwide and it is responsible for most cases of uterine cancer. In Ecuador there is limited information about HPV types (and variants) in cancerous lesions; however, identifying the type-specific HPV prevalence in cervical lesions of women living in Ecuador is important to better predict the impact of HPV prophylactic vaccination in this country. We studied the prevalence of HPV types in cervical cancerous or precancerous lesions from 164 Ecuadorian women and found that 86.0% were HPV positive. The most common types were HPV16 (41.8%) and HPV58 (30.5%). Interestingly, HPV18 was detected only in 2.8% of the HPV-positive samples. Fifteen DNA sequences (genes E6 and L1) from 16 samples positive for HPV16 belonged to the European lineage, considered one of the least carcinogenic lineages, and 1 (6.25%) to the Asian-American lineage. Similar analysis in 12 HPV58 positive samples showed that 10 (83.3%) sequences grouped in sublineage A2, which belongs to the oldest HPV58 lineage, 1 belonged to A3 and 1 to lineage C. This study suggests that the currently used HPV vaccines (bivalent and tetravalent) may have lower effectiveness in Ecuador than in other geographic locations where HPV18 is more prevalent.