HPV16 variant lineage, clinical stage, and survival in women with invasive cervical cancer

Tuller, Erin; Wentzensen, Nicolas; Mathews, Cara; Allen, Richard A.; Shanesmith, Rebecca; Dunn, S. Terence; Gold, Michael A.; Wang, Sophia; Walker, Joan L.; Schiffman, Mark

doi:10.1186/1750-9378-6-19

Cited by 28 publications

(22 citation statements)

References 20 publications

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“…In addition, our analysis revealed an increase in 350G allele frequency in samples from Central/South America compared with samples from Europe, consistent for all anatomical locations except for the vulva. This trend is in agreement with previous studies reporting an increased frequency of the 350G allele in Central/South America compared with European populations , as well as with the minor contribution of this allele in vulvar and in vaginal lesions .…”

Section: Discussionsupporting

confidence: 93%

HPV16 variants distribution in invasive cancers of the cervix, vulva, vagina, penis, and anus

et al. 2016

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Human papillomavirus (HPV)16 is the most oncogenic human papillomavirus, responsible for most papillomavirus‐induced anogenital cancers. We have explored by sequencing and phylogenetic analysis the viral variant lineages present in 692 HPV16‐monoinfected invasive anogenital cancers from Europe, Asia, and Central/South America. We have assessed the contribution of geography and anatomy to the differential prevalence of HPV16 variants and to the nonsynonymous E6 T350G polymorphism. Most (68%) of the variance in the distribution of HPV16 variants was accounted for by the differential abundance of the different viral lineages. The most prevalent variant (above 70% prevalence) in all regions and in all locations was HPV16_A1‐3, except in Asia, where HPV16_A4 predominated in anal cancers. The differential prevalence of variants as a function of geographical origin explained 9% of the variance, and the differential prevalence of variants as a function of anatomical location accounted for less than 3% of the variance. Despite containing similar repertoires of HPV16 variants, we confirm the worldwide trend of cervical cancers being diagnosed significantly earlier than other anogenital cancers (early fifties vs. early sixties). Frequencies for alleles in the HPV16 E6 T350G polymorphism were similar across anogenital cancers from the same geographical origin. Interestingly, anogenital cancers from Central/South America displayed higher 350G allele frequencies also within HPV16_A1‐3 lineage compared with Europe. Our results demonstrate ample variation in HPV16 variants prevalence in anogenital cancers, which is partly explained by the geographical origin of the sample and only marginally explained by the anatomical location of the lesion, suggesting that tissue specialization is not essential evolutionary forces shaping HPV16 diversity in anogenital cancers.

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Section: Discussionsupporting

confidence: 93%

HPV16 variants distribution in invasive cancers of the cervix, vulva, vagina, penis, and anus

et al. 2016

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“…We observed moderate differences in the RFS of ICC patients with different intratypic HPV 16 lineage groups ( p = 0.069), with the HPV 16 African B lineage group correlating with the worst RFS compared to the remaining lineages. This contrasts with the findings of Zuna et al ., who reported a statistically significant increased risk of death in patients harboring European variants compared to patients with non‐European variants . Their cohort consisted of 155 women with HPV 16‐positive ICC from the central United States, with a median follow up of 26.7 months .…”

Section: Discussionmentioning

confidence: 99%

Genetic variations in human papillomavirus and cervical cancer outcomes

Rader

Tsaih

Fullin

et al. 2019

Intl Journal of Cancer

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Cervical cancer is driven by persistent infection of human papillomavirus (HPV), which is influenced by HPV type and intratypic variants, yet the impact of HPV type and intratypic variants on patient outcomes is far less understood. Here, we examined the association of cervical cancer stage and survival with HPV type, clade, lineage, and intratypic variants within the HPV E6 locus. Of 1,028 HPV-positive cases recruited through the CerGE study, 301 were in-situ and 727 were invasive cervical cancer (ICC), with an average post-diagnosis follow-up of 4.8 years. HPV sequencing was performed using tumor-isolated DNA to assign HPV type, HPV 16 lineage, clade, and intratypic variants within the HPV 16 E6 locus, of which nonsynonomous variants were functionally annotated by molecular modeling. HPV 18-related types were more prevalent in ICC compared to in-situ disease and associated with significantly worse recurrence-free survival (RFS) compared to HPV 16-related types. The HPV 16 Asian American lineage D3 and Asian lineage A4 associated more frequently with ICC than with in situ disease and women with an intratypic HPV 16 lineage B exhibited a trend toward worse RFS than those with A, C, or D lineages. Participants with intratypic E6 variants predicted to stabilize the E6-E6AP-p53 complex had worse RFS. Variants within the highly immunogenic HPV 16 E6 region (E14-I34) were enriched in ICC compared to in-situ lesions but were not associated with survival. Collectively, our results suggest that cervical cancer outcome is associated with HPV variants that affect virus-host interactions.

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“…There is also multiple studies that indicate the HPV16 AA (D) lineage compared to the E (A) lineage is disproportionately (4–35 fold increased) associated with adenocarcinoma (AdCa) vs. squamous cell carcinoma (SCC) (Berumen et al, 2001; Burk et al, 2003; Quint et al, 2010; Zuna et al, 2011). Nevertheless, a study from Indonesian, Surinamese and Dutch cancer cases did not replicate this finding (De Boer et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Human papillomavirus genome variants

2013

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Amongst the human papillomaviruses (HPVs), the genus Alphapapillomavirus contains HPV types that are uniquely pathogenic. They can be classified into species and types based on genetic distances between viral genomes. Current circulating infectious HPVs constitute a set of viral genomes that have evolved with the rapid expansion of the human population. Viral variants were initially identified through restriction enzyme polymorphisms and more recently through sequence determination of viral fragments. Using partial sequence information, the history of variants, and the association of HPV variants with disease will be discussed with the main focus on the recent utilization of full genome sequence information for variant analyses. The use of multiple sequence alignments of complete viral genomes and phylogenetic analyses have begun to define variant lineages and sublineages using empirically defined differences of 1.0–10.0% and 0.5–1.0%, respectively. These studies provide the basis to define the genetics of HPV pathogenesis.

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HPV16 variant lineage, clinical stage, and survival in women with invasive cervical cancer

Cited by 28 publications

References 20 publications

HPV16 variants distribution in invasive cancers of the cervix, vulva, vagina, penis, and anus

HPV16 variants distribution in invasive cancers of the cervix, vulva, vagina, penis, and anus

Genetic variations in human papillomavirus and cervical cancer outcomes

Human papillomavirus genome variants

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