{"doi":"10.1101/2020.01.07.897546","title":"Human papillomavirus 16 positive cervical cancer in Guatemala: The D2 and D3 sublineages differ in integration rate and age of diagnosis","abstract":"Abstract Human papillomavirus (HPV) 16 displays substantial sequence variation; four HPV16 lineages (A, B, C, D) have been described, as well as multiple sub-lineages. To identify molecular events associated with HPV16 carcinogenesis we evaluated viral variation, the integration of HPV16, and somatic mutation in 96 cervical cancer samples from Guatemala. A total of 64% (60/94) of the samples had integrated HPV16 sequences, and integration was associated with an earlier age of diagnosis (P=0.0007) and pre-menopausal disease. HPV16 integration sites were broadly distributed in the genome but in one tumor, HPV16 integrated into the promoter of the interferon regulatory factor 4 ( IRF4 ) gene, which plays an important role in the regulation of the interferon response to viral infection. The HPV16 D2 and D3 sub-lineages were found in 23% and 30% of the tumors, respectively and were significantly associated with adenocarcinoma. D2-positive tumors had a higher rate of integration (P=0.011), earlier age of diagnosis (P=0.012), and a lower rate of somatic mutation (P=0.03). Whereas D3-positive tumors are less likely to integrate, have later age-of-diagnosis, and a higher rate of somatic mutation. In conclusion, Guatemalan cervical tumors have a high frequency of the very high-risk HPV16 D2 and D3 sub-lineages and cervical cancer patients with these variants of HPV16 differ in histology, age of- diagnosis, integration, and somatic mutation frequency. In summary, related lineages of HPV16 have different features of oncogenicity.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":126143,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8439,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":382570,"name":"Joseph F. 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Henry Garland","orcid":"0009-0005-7950-8898","position":10,"is_corresponding":false},{"id":293339,"name":"Sara Bass","orcid":null,"position":11,"is_corresponding":false},{"id":291036,"name":"Robert D. Burk","orcid":"0000-0002-8376-8458","position":12,"is_corresponding":false},{"id":291031,"name":"Meredith Yeager","orcid":"0000-0003-3871-2225","position":13,"is_corresponding":false},{"id":50161,"name":"Nicolas Wentzensen","orcid":"0000-0003-1251-0836","position":14,"is_corresponding":false},{"id":69966,"name":"Mark Schiffman","orcid":"0000-0002-4625-2508","position":15,"is_corresponding":false},{"id":574158,"name":"Enrique Alvirez","orcid":null,"position":16,"is_corresponding":false},{"id":382574,"name":"Eduardo Gharzouzi","orcid":"0000-0002-4223-867X","position":17,"is_corresponding":false},{"id":291037,"name":"Lisa Mirabello","orcid":"0000-0001-8485-0106","position":18,"is_corresponding":false},{"id":291441,"name":"Michael Dean","orcid":"0000-0003-2234-0631","position":19,"is_corresponding":false},{"id":384035,"name":"Hong Lou","orcid":null,"position":0,"is_corresponding":true}],"reference_count":39,"raw_metadata":null,"created_at":"2026-07-18T23:15:23.509897Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}