rs1118404 (HMHB1): HPV Seropositivity & Cervical Cancer
Key takeaways
- rs1118404 lies near the HMHB1 and RN7SL87P genes and was flagged in a genome-wide association study of HPV infection and cervical cancer risk.
- The variant did not reach genome-wide significance and is classified as a sub-threshold candidate.
- A validation study in a German cervical cancer cohort tested this and similar sub-threshold variants, but confirmed results for this specific variant are not available.
- The strongest genetic signals for HPV seropositivity and cervical cancer remain in the HLA region on chromosome 6.
Key takeaways
- rs1118404 lies near the HMHB1 and RN7SL87P genes and was flagged in a genome-wide association study (GWAS) of HPV infection and cervical cancer risk.
- The variant did not reach genome-wide significance and is classified as a sub-threshold candidate.
- A validation study in a German cervical cancer cohort tested this and similar sub-threshold variants, but confirmed results for this specific variant are not available.
- The strongest genetic signals for HPV seropositivity and cervical cancer remain in the HLA region on chromosome 6.
What the research says A GWAS of HPV16 seropositivity (n = 7,814), HPV18 seropositivity (n = 7,924), and combined HPV16/18 seropositivity (n = 7,924) in UK Biobank participants identified rs1118404, near the HMHB1 - RN7SL87P locus, as a sub-threshold variant at p < 5 × 10^-6. Twenty-four sub-threshold variants in total were subsequently genotyped in the German Cervigen cervical cancer and dysplasia case-control series, of which 11 showed nominal association with cervical disease, suggesting that sub-threshold seropositivity variants may collectively contribute to cervical cancer susceptibility.
Reported associations
- HPV seropositivity (sub-threshold signal): rs1118404 was flagged as a sub-threshold candidate (p < 5 × 10^-6) in a GWAS of HPV16 and/or HPV18 seropositivity in up to 7,924 European-ancestry UK Biobank participants; no confirmed effect size for this variant specifically is reported in the available study text.
- Cervical disease (validation cohort): The variant was included in a 24-variant validation panel genotyped in the German Cervigen cohort (n = 3,710 for overall cervical disease); whether rs1118404 was among the 11 variants showing nominal association with cervical disease is not specified in the available study text.
Evidence quality The discovery analysis used up to 7,924 UK Biobank participants of European ancestry. rs1118404 was among variants selected at a sub-genome-wide-significance threshold (p < 5 × 10^-6); the standard genome-wide significance bar of p < 5 × 10^-8 was not met. Validation genotyping was performed in the Cervigen cohort (n = 3,710 for overall cervical disease, n = 1,431 for HPV16-positive invasive cancer), but specific results for rs1118404 are not available from the provided study text. No odds ratio, beta coefficient, or independent replication confirmation is reported for this variant. Evidence for this locus must be considered preliminary and requires independent replication before conclusions can be drawn.
Lifestyle considerations No lifestyle considerations on file for this variant.
Lifestyle context
Concrete actions anchored to the cited research. We do not prescribe, we describe.
Discuss with your doctor
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HPV18 seropositivity and cancer risk implications Moderate
The G allele at rs1118404 is associated with HPV18 L1 seropositivity, indicating past or current HPV18 infection, which increases risk for cervical, anal, and oropharyngeal cancers.
Discuss HPV18 status, infection history, and cancer risk stratification with healthcare provider
Screening
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HPV-related cancer surveillance Moderate
HPV18 exposure from this variant increases cervical cancer risk in women and oropharyngeal and anal cancer risk in others; individualized screening based on sex and risk factors is appropriate.
Follow sex-specific and risk-based cancer screening guidelines for HPV-positive individuals
Frequently asked questions
What is rs1118404?
rs1118404 is a genetic variant located near the HMHB1 and RN7SL87P genomic region. It was identified as a sub-threshold candidate in a 2025 genome-wide association study examining HPV seropositivity and cervical cancer susceptibility in European populations.
Is rs1118404 linked to cervical cancer?
rs1118404 appeared in a genome-wide scan of HPV infection and cervical cancer risk, but it did not reach the genome-wide significance threshold (p < 5 × 10^-8). It was one of 24 sub-threshold candidates selected for validation genotyping in a German cohort, and no confirmed effect size has been reported for this specific variant.
What does the HMHB1 gene do in cervical cancer research?
The available study does not describe a specific function for HMHB1 in HPV infection or cervical cancer. Its proximity to rs1118404 makes it a candidate gene of interest, but no mechanistic evidence is provided in the current research.
How strong is the evidence linking rs1118404 to HPV seropositivity?
The evidence is preliminary. rs1118404 fell below the standard genome-wide significance threshold and was selected as a sub-threshold candidate for further validation. Independent replication of a specific effect at this locus has not been confirmed in the available study.
What were the main findings of the HPV seropositivity GWAS that identified rs1118404?
The GWAS identified genome-wide significant loci at 6p21.32 for HPV16 seropositivity and at 5q31.2 and 14q24.3 for HPV18 seropositivity, mostly in the HLA immune-response region. Additionally, 24 sub-threshold variants including rs1118404 were genotyped in a German validation cohort, and 11 showed nominal association with cervical disease.