PIK3CA Gene Mutations in HNSCC: Systematic Review and Correlations with HPV Status and Patient Survival
PIK3CA mutations are believed to contribute to the pathogenesis of human papillomavirus (HPV)-associated head and neck squamous cell carcinomas (HNSCC). This study aims to establish the frequency of PIK3CA mutations in a Portuguese HNSCC cohort and to determine their association with the HPV status...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-03-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/5/1286 |
| _version_ | 1797475493065261056 |
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| author | Daniela Cochicho Susana Esteves Miguel Rito Fernanda Silva Luís Martins Pedro Montalvão Mário Cunha Miguel Magalhães Rui M. Gil da Costa Ana Felix |
| author_facet | Daniela Cochicho Susana Esteves Miguel Rito Fernanda Silva Luís Martins Pedro Montalvão Mário Cunha Miguel Magalhães Rui M. Gil da Costa Ana Felix |
| author_sort | Daniela Cochicho |
| collection | DOAJ |
| description | PIK3CA mutations are believed to contribute to the pathogenesis of human papillomavirus (HPV)-associated head and neck squamous cell carcinomas (HNSCC). This study aims to establish the frequency of PIK3CA mutations in a Portuguese HNSCC cohort and to determine their association with the HPV status and patient survival. A meta-analysis of scientific literature also revealed widely different mutation rates in cohorts from different world regions and a trend towards improved prognosis among patients with PIK3CA mutations. DNA samples were available from 95 patients diagnosed with HNSCC at the Portuguese Institute of Oncology in Lisbon between 2010 and 2019. HPV status was established based on viral DNA detected using real-time PCR. The evaluation of PIK3CA gene mutations was performed by real-time PCR for four mutations (H1047L; E542K, E545K, and E545D). Thirty-seven cases were found to harbour PIK3CA mutations (39%), with the E545D mutation (73%) more frequently detected. There were no significant associations between the mutational status and HPV status (74% WT and 68% MUT were HPV (+); <i>p</i> = 0.489) or overall survival (OS) (3-year OS: WT 54% and MUT 65%; <i>p</i> = 0.090). HPV status was the only factor significantly associated with both OS and disease-free survival (DFS), with HPV (+) patients having consistently better outcomes (3-year OS: HPV (+) 65% and HPV (−) 36%; <i>p</i> = 0.007; DFS HPV (+) 83% and HPV (−) 43%; <i>p</i> = 0.001). There was a statistically significant interaction effect between HPV status and PIK3CA mutation regarding DFS (Interaction test: <i>p</i> = 0.026). In HPV (+) patients, PIK3CA wild-type is associated with a significant 4.64 times increase in the hazard of recurrence or death (HR = 4.64; 95% CI 1.02–20.99; <i>p</i> = 0.047). Overall, PIK3CA gene mutations are present in a large number of patients and may help define patient subsets who can benefit from therapies targeting the PI3K pathway. The systematic assessment of PIK3CA gene mutations in HNSCC patients will require further methodological standardisation. |
| first_indexed | 2024-03-09T20:44:55Z |
| format | Article |
| id | doaj.art-9dbe6b78e9ae4feea4819f99e66c1cc5 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T20:44:55Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-9dbe6b78e9ae4feea4819f99e66c1cc52023-11-23T22:48:43ZengMDPI AGCancers2072-66942022-03-01145128610.3390/cancers14051286PIK3CA Gene Mutations in HNSCC: Systematic Review and Correlations with HPV Status and Patient SurvivalDaniela Cochicho0Susana Esteves1Miguel Rito2Fernanda Silva3Luís Martins4Pedro Montalvão5Mário Cunha6Miguel Magalhães7Rui M. Gil da Costa8Ana Felix9NOVA Medical School, NOVA University of Lisbon, 1099-085 Lisbon, PortugalClinical Research Unit, IPOLFG, 1099-023 Lisbon, PortugalPathology Department, IPOLFG, 1099-023 Lisbon, PortugalNOVA Medical School, NOVA University of Lisbon, 1099-085 Lisbon, PortugalVirology Laboratory from Clinical Pathology Department, IPOLFG, 1099-023 Lisbon, PortugalOtorhinolaryngology Department, IPOLFG, 1099-023 Lisbon, PortugalVirology Laboratory from Clinical Pathology Department, IPOLFG, 1099-023 Lisbon, PortugalOtorhinolaryngology Department, IPOLFG, 1099-023 Lisbon, PortugalPost-Graduate Programme in Adult Health (PPGSAD), Morphology Department, University Hospital (HUUFMA), Federal University of Maranhão, São Luís 65080-805, BrazilNOVA Medical School, NOVA University of Lisbon, 1099-085 Lisbon, PortugalPIK3CA mutations are believed to contribute to the pathogenesis of human papillomavirus (HPV)-associated head and neck squamous cell carcinomas (HNSCC). This study aims to establish the frequency of PIK3CA mutations in a Portuguese HNSCC cohort and to determine their association with the HPV status and patient survival. A meta-analysis of scientific literature also revealed widely different mutation rates in cohorts from different world regions and a trend towards improved prognosis among patients with PIK3CA mutations. DNA samples were available from 95 patients diagnosed with HNSCC at the Portuguese Institute of Oncology in Lisbon between 2010 and 2019. HPV status was established based on viral DNA detected using real-time PCR. The evaluation of PIK3CA gene mutations was performed by real-time PCR for four mutations (H1047L; E542K, E545K, and E545D). Thirty-seven cases were found to harbour PIK3CA mutations (39%), with the E545D mutation (73%) more frequently detected. There were no significant associations between the mutational status and HPV status (74% WT and 68% MUT were HPV (+); <i>p</i> = 0.489) or overall survival (OS) (3-year OS: WT 54% and MUT 65%; <i>p</i> = 0.090). HPV status was the only factor significantly associated with both OS and disease-free survival (DFS), with HPV (+) patients having consistently better outcomes (3-year OS: HPV (+) 65% and HPV (−) 36%; <i>p</i> = 0.007; DFS HPV (+) 83% and HPV (−) 43%; <i>p</i> = 0.001). There was a statistically significant interaction effect between HPV status and PIK3CA mutation regarding DFS (Interaction test: <i>p</i> = 0.026). In HPV (+) patients, PIK3CA wild-type is associated with a significant 4.64 times increase in the hazard of recurrence or death (HR = 4.64; 95% CI 1.02–20.99; <i>p</i> = 0.047). Overall, PIK3CA gene mutations are present in a large number of patients and may help define patient subsets who can benefit from therapies targeting the PI3K pathway. The systematic assessment of PIK3CA gene mutations in HNSCC patients will require further methodological standardisation.https://www.mdpi.com/2072-6694/14/5/1286HNSCCHPVp16 INK4aPIK3CA |
| spellingShingle | Daniela Cochicho Susana Esteves Miguel Rito Fernanda Silva Luís Martins Pedro Montalvão Mário Cunha Miguel Magalhães Rui M. Gil da Costa Ana Felix PIK3CA Gene Mutations in HNSCC: Systematic Review and Correlations with HPV Status and Patient Survival Cancers HNSCC HPV p16 INK4a PIK3CA |
| title | PIK3CA Gene Mutations in HNSCC: Systematic Review and Correlations with HPV Status and Patient Survival |
| title_full | PIK3CA Gene Mutations in HNSCC: Systematic Review and Correlations with HPV Status and Patient Survival |
| title_fullStr | PIK3CA Gene Mutations in HNSCC: Systematic Review and Correlations with HPV Status and Patient Survival |
| title_full_unstemmed | PIK3CA Gene Mutations in HNSCC: Systematic Review and Correlations with HPV Status and Patient Survival |
| title_short | PIK3CA Gene Mutations in HNSCC: Systematic Review and Correlations with HPV Status and Patient Survival |
| title_sort | pik3ca gene mutations in hnscc systematic review and correlations with hpv status and patient survival |
| topic | HNSCC HPV p16 INK4a PIK3CA |
| url | https://www.mdpi.com/2072-6694/14/5/1286 |
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