# HPV16 E6 Antibody Detection as an Early Marker for Oropharyngeal Cancer Among Men Living with HIV

> **NIH NIH R01** · UNIVERSITY OF KENTUCKY · 2020 · $650,620

## Abstract

People living with HIV (PLWH) have an increased life expectancy due to effective therapies. This has resulted in an
increased incidence of non-AIDS defining cancers (NADCs), in particular, cancers caused by human papillomavirus (HPV).
The most rapidly increasing HPV-related malignancy in the general US population is HPV-driven oropharyngeal cancer
(HPV-OPC), a type of head and neck that has increased in incidence by more than 200% over the past few decades.1, 2
PLWH are 1.5 to 4 times more likely to develop HPV-OPC than the general population.3 They are also more likely to
develop HPV-OPC at younger ages (51 versus 60)4 and have a less favorable cancer prognoses.5 Unlike cervical cancer,
where the introduction of highly effective screening has significantly reduced the incidence and mortality of cervical
cancer, there are no methods for early detection of HPV-OPC. A major barrier for early detection has been the inability
to identify PLWH at highest risk for HPV-OPC given that a precancerous precursor lesion for OPC has yet to be identified.
Recently, HPV16 E6 antibody positivity has been identified as a promising early biomarker. Previous work from our
group showed that HPV16 E6 antibodies are present in up to 90% of HPV-OPC patients6 and appear more than 10 years
prior to diagnosis.7-9 Additionally, we have shown that HPV16 E6 antibodies are highly specific for HPV-OPC10 and are not
strongly associated with the 5 other cancers caused by HPV.11 The objective of this study is to evaluate the ability of the
HPV16 E6 marker to identify a sub-population of PLWH at highest risk for developing HPV-OPC and for which head and
neck cancer screening would be most effective. To accomplish this, we will conduct a natural history study of the HPV16
E6 antibody marker. This study will focus on men aged 40+ living with HIV given that ~85% of HPV-OPC cases occur in
middle aged men and HIV infection additionally elevates risk by up to 4-fold. Using the Tennessee Center for AIDS
Research (TN-CFAR) Biorepository, banked blood samples from men aged 40+ living with HIV (N=3,261) will be tested for
HPV16 E6 antibodies. All HPV16 E6 seropositives and a subset of HPV16 E6 seronegatives (1:2 ratio) will be invited to
participate in yearly (4 total) comprehensive head and neck cancer screening exams performed by a Vanderbilt Ingram
Cancer Center (VICC) head and neck surgeon. Cancer screening visits will include: visual inspection of the mouth and
palpation of tonsils, ultrasound imaging, laryngoscope exam, a detailed questionnaire and biospecimen collection. E6
seropositive men will be compared to E6 seronegative men in terms of: a) markers of elevated HPV-OPC risk and b)
development of HPV-OPC. The specific aims are: (1) Estimate the prevalence of HPV16 E6 antibodies among men aged
40+ living with HIV; (2) Determine the association between HPV16 E6 seropositivity and markers of HPV-OPC risk; (3)
Estimate the risk of developing: a) precancerous markers of HPV-OPC and/or;...

## Key facts

- **NIH application ID:** 10339080
- **Project number:** 7R01DE029650-02
- **Recipient organization:** UNIVERSITY OF KENTUCKY
- **Principal Investigator:** Krystle A. Kuhs
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $650,620
- **Award type:** 7
- **Project period:** 2021-02-05 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10339080

## Citation

> US National Institutes of Health, RePORTER application 10339080, HPV16 E6 Antibody Detection as an Early Marker for Oropharyngeal Cancer Among Men Living with HIV (7R01DE029650-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10339080. Licensed CC0.

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