Lineages of Oncogenic Human Papillomavirus Types Other Than Type 16 and 18 and Risk for Cervical Intraepithelial Neoplasia

Xi, Long Fu; Schiffman, Mark; Koutsky, Laura A.; Mao, Constance; Hulbert, Ayaka; Lee, Shu Kuang; Shen, Zhenping; Kiviat, Nancy B.

doi:10.1093/jnci/dju270

Cited by 42 publications

(57 citation statements)

References 53 publications

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“…The present study is an extension of our previous observation that risks of CIN2/3 differed significantly by variant lineages of HPV types 31/33/45/56/58 . In this study of women with these HPV types newly detected during a 2‐year follow‐up, we found that infections with HR, compared with non‐HR, variants tended to be marginally more likely to become negative.…”

Section: Discussionsupporting

confidence: 68%

“…Despite a high degree of DNA sequence homology between HPV variants, some differ in their group phenotypic traits. We previously analyzed intratypic diversity of oncogenic types other than HPV16 and HPV18, showing that risks of cervical precancer, defined clinically as cervical intraepithelial neoplasia Grades 2–3 (CIN2/3) differed significantly by variant lineages of five types ( i.e ., HPV31, HPV33, HPV45, HPV56 and HPV58) . We have postulated that genetic changes accumulated in the long‐term viral evolution may have altered certain biologic properties of the virus which are responsible for the observed risk difference.…”

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confidence: 99%

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Variant‐specific persistence of infections with human papillomavirus Types 31, 33, 45, 56 and 58 and risk of cervical intraepithelial neoplasia

Schiffman

Koutsky

et al. 2016

Intl Journal of Cancer

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In our previous study of the etiologic role of oncogenic human papillomavirus (HPV) types other than HPV16 and 18, we observed a significantly higher risk of cervical intraepithelial neoplasia grades 2-3 (CIN2/3) associated with certain lineages of HPV types 31/33/45/56/58 (called high-risk (HR) variants) compared with non-HR variants. This study was to examine whether these intra-type variants differ in persistence of the infection and persistence-associated risk of CIN2/3. Study subjects were women who had any of HPV types 31/33/45/56/58 newly detected during a 2-year follow-up with 6-month intervals. For each type, the first positive sample was used for variant characterization. The association of reverting-to-negativity with group of the variants and CIN2/3 with length of positivity was assessed using discrete Cox regression and logistic regression, respectively. Of the 598 newly detected, type-specific HPV infections, 312 became undetectable during follow-up. Infections with HR, compared with non-HR, variants were marginally more likely to become negative (adjusted hazard ratio = 1.3; 95% confidence interval (CI), 0.9-1.8). The adjusted odds ratio associating with the development of CIN2/3 was 3.0 (95% CI, 1.2-7.4) for persistent infections with HR variants for 6 months and 10.0 (95% CI, 3.8-38.0) for persistent infections with HR variants for 12-18 months as compared with the first positive detection of HR variants. Among women with non-HR variants, there were no appreciable differences in risk of CIN2/3 by length of positivity. Findings suggest that the lineage-associated risk of CIN2/3 was not mediated through a prolonged persistent infection, but oncogenic heterogeneity of the variants.

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Section: Discussionsupporting

confidence: 68%

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confidence: 99%

Variant‐specific persistence of infections with human papillomavirus Types 31, 33, 45, 56 and 58 and risk of cervical intraepithelial neoplasia

Schiffman

Koutsky

et al. 2016

Intl Journal of Cancer

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“…Methods for PCR sequencing and analysis were described previously. 13, 14 If ≥1 nucleotide alteration was detected among type-specific isolates in different samples from one woman, they were considered to be different variants. In analyses, paired samples with different variants were considered discordant; if variant results were unavailable, paired samples positive for the same HPV type were assumed to be concordant.…”

Section: Methodsmentioning

confidence: 99%

Epidemiology of Human Papillomavirus Detected in the Oral Cavity and Fingernails of Mid-Adult Women

Fu¹,

Feng²,

Hulbert³

et al. 2015

Sexually Transmitted Diseases

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Background Oral and fingernail human papillomavirus (HPV) detection may be associated with HPV-related carcinoma risk at these non-genital sites and foster transmission to the genitals. We describe the epidemiology of oral and fingernail HPV among mid-adult women. Methods Between 2011–2012, 409 women aged 30–50 years were followed for 6 months. Women completed health and behavior surveys and provided self-collected oral, fingernail, and vaginal specimens at enrollment and exit for type-specific HPV DNA testing. Concordance of type-specific HPV detection across anatomic sites was described with kappa statistics. Using generalized estimating equations or exact logistic regression, we measured the univariate associations of various risk factors with type-specific oral and fingernail HPV detection. Results Prevalence of detecting HPV in the oral cavity (2.4%) and fingernails (3.8%) was low compared to the vagina (33.1%). Concordance across anatomic sites was poor (kappa<.20 for all comparisons). However, concurrent vaginal infection with the same HPV type (OR=101.0;95%CI: 31.4–748.6) and vaginal HPV viral load (OR per one log10 viral load increase=2.2;95%CI:1.5–5.5) were each associated with fingernail HPV detection. Abnormal Pap history (OR=11.1;95%CI:2.8-infinity), lifetime number of male vaginal sex partners ≥10 (OR vs. 0–3 partners=5.0;95%CI:1.2-infinity), and lifetime number of open-mouth kissing partners ≥16 (OR vs. 0–15 partners=infinity;95%CI:2.6-infinity, by exact logistic regression) were each associated with oral HPV detection. Conclusions While our findings support HPV DNA deposition or autoinoculation between anatomic sites in mid-adult women, the rarity of HPV in the oral cavity and fingernails suggests that oral/fingernail HPV does not account for a significant fraction of HPV in genital sites.

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“…Whole-genome sequence analysis of HPV45 strains has led to the delineation of distinct variant lineages (A and B) and sublineages (A1, A2, A3, B1, and B2) (3,6,7), with the possibility of a lineage C suggested from subgenomic sequences (8). Although firm data on their contribution to the risk of cervical disease progression are lacking, in part due to the low relative prevalences of individual lineages and sublineages in the population, current evidence does support some lineage-specific bias such that sublineage variant B2 (and possibly A3) appears to be overrepresented in patients with high-grade disease compared to controls (8)(9)(10). There may also be some geographical bias to the distribution of HPV45 sublineages (9).…”

Section: ϫ8mentioning

confidence: 99%

Naturally Occurring Major and Minor Capsid Protein Variants of Human Papillomavirus 45 (HPV45): Differential Recognition by Cross-Neutralizing Antibodies Generated by HPV Vaccines

Godi

Facchetti

Bissett

et al. 2016

J Virol

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cWe investigated naturally occurring variation within the major (L1) and minor (L2) capsid proteins of human papillomavirus genotype 45 (HPV45). Pseudoviruses (PsVs) representing HPV45 sublineages A1, A2, A3, B1, and B2 exhibited comparable particle-to-infectivity ratios and morphologies but demonstrated both increased (A2, A3, and B1) and decreased (B2) sensitivities to cross-neutralization by HPV vaccine antibodies compared to that of the A1 sublineage. Mutant PsVs identified HI loop residue 357 as being critical for conferring this differential sensitivity. The evolutionary mutation rate of the human papillomavirus (HPV) double-stranded DNA genome is low at ca. 2 ϫ 10 Ϫ8 base substitutions per site per year (1, 2), yet distinct genotypes and intragenotype variant lineages have arisen over time (3). HPV genotype 45 (HPV45) is closely related to HPV18 within the Alpha-7 species group and is associated with ca. 5% of cervical cancer cases worldwide (4, 5). Whole-genome sequence analysis of HPV45 strains has led to the delineation of distinct variant lineages (A and B) and sublineages (A1, A2, A3, B1, and B2) (3, 6, 7), with the possibility of a lineage C suggested from subgenomic sequences (8). Although firm data on their contribution to the risk of cervical disease progression are lacking, in part due to the low relative prevalences of individual lineages and sublineages in the population, current evidence does support some lineage-specific bias such that sublineage variant B2 (and possibly A3) appears to be overrepresented in patients with high-grade disease compared to controls (8-10). There may also be some geographical bias to the distribution of HPV45 sublineages (9). Intragenotypic variation occurs throughout the HPV genome, but the consequences of these polymorphisms on the functions of the resulting gene products are uncertain.The HPV structural genes encode the major (L1) and minor (L2) capsid proteins. The L1 protein multimerizes to form the nonenveloped icosahedral viral capsid (comprising 72 L1 pentameric capsomers) that mediates attachment to host cells (11), while the L2 protein is essential for viral infectivity (12). Structural alterations of the external surface topography of L1 can be conferred by minor sequence differences between genotypes (13), supporting observations that almost all neutralizing monoclonal antibodies (MAbs) that target these external surfaces are type specific (14-17). Nevertheless, functional antibody cross-reactivity is a common feature of sera from recipients of the Cervarix (bivalent) and Gardasil (quadrivalent) vaccines (18-22) and may be responsible for conferring HPV vaccine-induced cross-protection (23).It is reasonable to consider that lineage-specific variation in surface-exposed domains (7, 24, 25) may influence capsid recognition by HPV vaccine-derived antibodies. Single-cycle replication-incompetent pseudoviruses (PsVs) representing HPV16 L1, but not L2, variants (26) appear to exhibit little difference in their susceptibilities to type-specific antibodies eli...

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Lineages of Oncogenic Human Papillomavirus Types Other Than Type 16 and 18 and Risk for Cervical Intraepithelial Neoplasia

Abstract: These findings suggest that for a given HPV type, intratypic nucleotide changes may alter phenotypic traits that affect the probability of neoplasia.

Cited by 42 publications

References 53 publications

Variant‐specific persistence of infections with human papillomavirus Types 31, 33, 45, 56 and 58 and risk of cervical intraepithelial neoplasia

Variant‐specific persistence of infections with human papillomavirus Types 31, 33, 45, 56 and 58 and risk of cervical intraepithelial neoplasia

Epidemiology of Human Papillomavirus Detected in the Oral Cavity and Fingernails of Mid-Adult Women

Naturally Occurring Major and Minor Capsid Protein Variants of Human Papillomavirus 45 (HPV45): Differential Recognition by Cross-Neutralizing Antibodies Generated by HPV Vaccines

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