HPV16 Sublineage Associations With Histology-Specific Cancer Risk Using HPV Whole-Genome Sequences in 3200 Women

Mirabello, Lisa; Yeager, Meredith; Cullen, Michael; Boland, Joseph F.; Chen, Zigui; Wentzensen, Nicolas; Zhang, Xijun; Yu, Kai; Yang, Qi; Mitchell, Jason; Roberson, David A.; Bass, Sara; Xiao, Yanzi; Burdett, Laurie; Raine‐Bennett, Tina; Lorey, Thomas; Castle, Philip E.; Burk, Robert D.; Schiffman, Mark

doi:10.1093/jnci/djw100

Cited by 172 publications

(253 citation statements)

References 46 publications

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“…Differences in the oncogenic potential displayed by variants of the same HPV type have been described; HPV16 B, C, D2 and D3 variants promote a 3-fold higher risk of cervical cancer development compared to the A1 sublineage. The non-European HPV18 variants are identified more frequently in cancer tissues and high-grade squamous lesions [31,34,35,36]. HPV33 (C7732G) and HPV58 (C632T and G760A) variants have been associated with a higher risk of cervical cancer development [37,38].…”

Section: Hpv Diversity and Cancermentioning

confidence: 99%

“…HPV33 (C7732G) and HPV58 (C632T and G760A) variants have been associated with a higher risk of cervical cancer development [37,38]. In addition, the HPV16 D2 and D3 sublineages are associated with adenocarcinoma [36,39]. Some studies suggest that a higher risk for cervical cancer development is not only related to the HPV variant/sublineage, but also dependent on ethnicity.…”

Section: Hpv Diversity and Cancermentioning

confidence: 99%

“…A study that analyzed the risk of CIN3+ development in women infected by HPV16 according to ethnicity shows that white women infected by the HPV16 A1/A2 sublineages have a higher risk of CIN3+ compared to all women from other ethnicities. In contrast, this risk is higher for Asian women with HPV16 A4 infection and Hispanic women with the D2/D3 infection sublineages [36]. Moreover, rare cases of cervical cancer in which the only HPV type isolated was a low-risk HPV have been described [19,40], suggesting a particular susceptibility in the host.…”

Section: Hpv Diversity and Cancermentioning

confidence: 99%

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The Biological Impact of Genomic Diversity in Cervical Cancer Development

Oliveira¹,

Levi²

2016

Acta Cytologica

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Human papillomaviruses (HPVs) are the etiologic agents of cervical cancer, the unique human neoplasia that has one single necessary cause. The diversity of HPVs is well described, with 200 HPV types existing as distinct taxonomic units and each receiving an Arabic number. On a clinical basis, they are usually grouped by their site of occurrence and disease associations. Those types inhabiting the anogenital mucosa are more intensively studied and further divided into cancer-associated HPVs, which are termed ‘high risk', while those linked to benign proliferative lesions are assigned as ‘low risk'. HPV16 is responsible for approximately 50% of all ICC cases, and paradoxically is one of the most prevalent types among healthy women. Longitudinal studies have shown that when an incidental HPV16 infection becomes persistent it will result in an enhanced risk for the development of high-grade lesions. However, it is unknown why some persistent, HPV16 infections (or infections by other HR-HPV types) progress to CIN3+ while most clear spontaneously. Several epidemiological investigations have focused on cofactors, from the most obvious such as cigarette and other carcinogenic exposures, to coinfections by other STDs such as chlamydia, with no significant findings. Thus, the current focus is on genomic variation from both virus and host. Such studies have been potentialized by the enormous technical advances in nucleic acid sequencing, allowing this relationship to be broadly interrogated. Corroborating subgenomic data from decades ago, an association between HPV16 lineages and carcinogenesis is being revealed. However, this effect does not seem to apply across female populations from different continents/ethnicities, again highlighting a role played by HPV16 adaptation and evasion from the host over time.

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Section: Hpv Diversity and Cancermentioning

confidence: 99%

Section: Hpv Diversity and Cancermentioning

confidence: 99%

Section: Hpv Diversity and Cancermentioning

confidence: 99%

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The Biological Impact of Genomic Diversity in Cervical Cancer Development

Oliveira¹,

Levi²

2016

Acta Cytologica

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“…However, persistent infections with certain variants of HPV16, the genotype found in approximately half of all cervical cancers [4], differ in cancer risk. These variants diverge in their biological properties; therefore, they may become important risk factors in cervical cancer because of possible differences in pathogenicity [5][6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%

“…Thus, sublineage A1 can be divided into isolates containing either 350T (EUR-350T, which includes the prototype HPV16 sequence) or 350G (EUR-350G). Epidemiological studies have suggested that this polymorphism might promote persistent viral infection and cervical cancer development [8,9,14,15]: HPV16 variants with mutations in E6 have been reported for cervical High-grade Squamous Intraepithelial Lesions (HSIL), invasive cervical cancer, and anal HSIL [16][17][18][19][20]. More precisely, in epidemiological study of the French population, a specific intratype polymorphism, such as the EUR-350G isolate, has been found to induce a greater risk of persistence and progression than the E6 prototype [8].…”

Section: Introductionmentioning

confidence: 99%

Relationship between E6-E7 lineage sequences, viral loads, and integration of HPV16 in women with atypical squamous cells of undetermined significance (ASCUS) pap smears

Loubatier¹,

Monte²,

Cannavo³

et al. 2018

Obstet Gynecol Rep

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HPV16 DNA associated with histologic high-grade precancer lesions (cervical intraepithelial neoplasia grade 2 or 3 [CIN2 or CIN3]) is sometimes found in women with atypical squamous cells of undetermined significance (ASCUS) Pap smears, the mildest form of cellular abnormality in a cervical smear. This study evaluated, in a population of patients with ASCUS Pap smears, the prevalence of different HPV16 lineages (or isolates) and the physical status, total viral load, and integrated viral load of HPV16 DNA in a population, stratified by HPV16 isolates (primarily either EUR-350T or EUR-350G) that was found. We demonstrated, in smears of women diagnosed with ASCUS and infected with EUR-350G HPV16 isolates (sublineage A1) that both the physical status of HPV16 and the distribution of integrated HPV16 DNA viral loads were different when compared to a population infected with EUR-350T HPV16 isolates. We showed that the mean and median percentages of HPV16 DNA were higher, and a distribution of log 10 integrated HPV16 viral load was more homogeneous in a population infected with EUR-350G HPV16 isolates than in a population infected with EUR-350T HPV16 isolates. No difference was found in terms of total HPV16 viral load between these two isolates. Here, we investigate E6-E7 sequencing as an easy technique to detect women with a greater proportion of integrated HPV genome, and we suggest an adaptation of the current protocol for monitoring women with ASCUS Pap smears.

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Papillomaviruses and Cervical Neoplasia

Herfs¹,

Crum²,

Münger³

2022

Holland‐Frei Cancer Medicine

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Overview Even after the 2008 Nobel prize awarded to Prof. Harald zur Hausen, the field of HPV continues to advance rapidly with new insights into pathogenesis, the discovery of novel genotypes/variants, refined screening approaches using HPV testing, and the recent commercialization of vaccines covering several carcinogenic HPV types. The squamocolumnar junction, which is involved in approximately 90% of (pre)neoplastic lesions, has been more precisely characterized, and its potential as a target for prevention in women beyond optimal age for vaccination is being discussed. HPV testing is assuming a major role in screening women over the age of 30, at the expense of the Papanicolaou smear, which will be largely limited to women between age 20 and 30, with a reduction or the elimination of cervical screening for women under the age of 20. For prevention of cervical neoplasia, new broader spectrum vaccines (such as a 9‐valent vaccine) were introduced allowing for targeting of extended range of high‐risk HPVs.

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HPV16 Sublineage Associations With Histology-Specific Cancer Risk Using HPV Whole-Genome Sequences in 3200 Women

Abstract: Specific HPV16 variant sublineages strongly influence risk of histologic types of precancer and cancer, and viral genetic variation may help explain its unique carcinogenic properties.

Cited by 172 publications

References 46 publications

The Biological Impact of Genomic Diversity in Cervical Cancer Development

The Biological Impact of Genomic Diversity in Cervical Cancer Development

Relationship between E6-E7 lineage sequences, viral loads, and integration of HPV16 in women with atypical squamous cells of undetermined significance (ASCUS) pap smears

Papillomaviruses and Cervical Neoplasia

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