Abstract
Individuals living with HIV are at a higher risk for developing human papillomavirus-driven oropharyngeal squamous cell carcinoma (HPV+OPSCC). There are no methods for early detection; however, HPV16 E6 antibodies have been identified as a promising early marker. The objective of this study was to evaluate the prevalence of HPV16 E6 antibodies among men living with HIV, with secondary objectives of analyzing clinical and serologic predictors of HPV16 E6 seropositivity. Banked blood specimens from 2,320 men aged 40+ living with HIV in Tennessee were evaluated for the following HPV16 antibodies: L1, E1, E2, E4, E6, E7. HPV16 E6 antibody levels were further categorized as moderate or high. Demographic, clinical, and serologic determinants of HPV16 E6 seropositivity were evaluated using logistic regression. HPV16 L1 antibodies were most common (22.8%), followed by E4 (10.5%), E6 (5.6%), E2 (4.8%), and E7 (4.0%). Of the 130 HPV16 E6 seropositives, 55 (2.4%) had moderate seropositivity and 75 (3.2%) had high. HPV16 E6 seropositive men had nearly 2-fold greater odds of seropositivity against one additional HPV16 E antigen (OR: 1.67 [95% CI: 1.10-2.52]; P=0.015) and over 3-fold greater odds of seroreactivity against two additional HPV16 E antigens (OR: 3.21 [95% CI: 1.40-7.33]; P=0.006). HPV16 E6 seropositivity was not associated with the clinical or demographic factors evaluated. In the largest study to date, HPV16 E6 seroprevalence was elevated compared to prior studies in HIV populations (range: 1.1% to 3.2%) and likely reflects the high incidence of HPV+OPSCC in the southeast region of the United States.
Keywords: Human papillomavirus, HPV, serology, HPV16 E6 antibodies
INTRODUCTION
The most rapidly increasing human papillomavirus (HPV)-related malignancy in the general US population is HPV-driven oropharyngeal squamous cell carcinoma (HPV+OPSCC), which has increased in incidence by more than 200% over the past few decades.1,2 People living with HIV (PWH) are 1.5 to 4 times more likely to develop HPV+OPSCC than their HIV-negative counterparts,3 develop HPV+OPSCC at younger ages (51 versus 60)4 and have a less favorable prognosis.5
Unlike cervical cancer, where highly effective screening methods have reduced the incidence of and mortality due to cervical cancer, there are no methods for early detection of HPV+OPSCC. A major barrier to developing screening methods for HPV+OPSCC is that a precancerous lesion for HPV+OPSCC has yet to be identified, making it difficult to identify PLWH who are at high risk for HPV+OPSCC and for whom screening may be beneficial. However, our group discovered a highly sensitive and specific blood biomarker that may indicate those at the highest risk for developing HPV+OPSCC. Our group has shown that antibodies directed against the E6 oncoprotein of HPV16 are present in approximately 90% of HPV+OPSCC patients6 and appear more than ten years before diagnosis.7–9 Additionally, HPV16 E6 antibodies are rare among those without cancer (0.7%)10 and are not strongly associated with the five other cancers caused by HPV.11 Despite the increased risk of developing HPV+OPSCC for those with HIV, of the approximately 36 studies of HPV16 E6 seropositivity conducted to date, only six evaluated HPV16 E6 seroprevalence in PWH.10–15 Prior studies among PWH were conducted in the United States (US), Switzerland and Australia, and reported estimates ranging from 1.1% to 3.2%.10–15 None included the southeast region of the US – an area with exceptionally high HPV+OPSCC incidence. These gaps in our understanding must be addressed before considering HPV16 E6 seropositivity as a potential screening tool.
To better understand whether the HPV16 E6 antibody marker has potential clinical utility for early detection of HPV+OPSCC in PWH, our group is conducting a large screening study of men aged 40+ living in the southeast region of the United States. We have completed phase one of the study, which involved HPV16 E6 antibody testing of 2,320 men aged 40+ living with HIV who provided a research blood specimen to the Tennessee Center for AIDS Research (TN-CFAR) biorepository. In phase two, which is currently ongoing, all HPV16 E6 seropositive men and a subset of seronegatives are invited to undergo a full head and neck cancer screening exam. This current analysis presents findings from phase one of the study, the main objective of which was to evaluate HPV16 E6 seroprevalence among men living with HIV. We evaluated demographic, clinical, and serologic predictors of HPV16 E6 seropositivity as a secondary objective. To our knowledge, this is the largest study of PWH conducted to date and the first to evaluate HPV serology among PHW residing in the Southeastern US.
METHODS
Study Population
HIV-ENDEAVOR is a natural history study of the HPV16 E6 antibody marker to evaluate the ability of the HPV16 E6 marker to identify a sub-population of PWH at highest risk for developing HPV+OPSCC and for which screening may be effective. HIV-ENDEAVOR is organized into two phases. For phase one, all available blood specimens banked within the Tennessee Center for AIDS Research (TN-CFAR) biorepository (IRB#008502) between 2001 and 2019 from men living with HIV aged 40+ (N=2,320) underwent HPV multiplex serology. Inclusion criteria for this study included: male sex at birth, living with HIV, aged 40+, and no prior history of OPSCC. Briefly, the TN-CFAR biorepository banks research blood specimens from patients at the Vanderbilt Comprehensive Care Clinic (VCCC), the largest provider of HIV care in Middle Tennessee. Patients were approached at their appointment and asked if they were willing to participate in the biorepository. For those who consented, an extra tube of blood was drawn during their normal labs. In phase 2, all HPV16 E6 seropositives and a subset seronegatives (1:2 ratio) are invited to participate in yearly head and neck cancer screening exams. The screening exams include physical and visual inspection, ultrasound imaging, laryngoscope exam, a detailed questionnaire and biospecimen collection.
This current analysis presents findings from phase one of the study. Every available sample in the biorepository was tested regardless of clinical information to mitigate potential bias in our HPV seroprevalence estimates, as this was the primary aim of the study, and analyzing predictors of seropositivity was a secondary aim of the study. This study only considered the current age of participants (as of 2022); thus, 17% of participants had a blood specimen banked before age 40. This study was reviewed and approved by the Vanderbilt Institutional Review Board (IRB#191031); all participants provided written informed consent. To protect participants’ rights, privacy, and welfare, the Vanderbilt IRB conducted a thorough review of this study to ensure that the research complied with federal, state, and institutional regulations, including, but not limited to, the Belmont Report, Declaration of Helsinki and the US Common Rule.
Serologic Testing
Banked serum samples were shipped to German Cancer Research Center (DKFZ) for blinded analysis. Seroreactivity against the HPV16 proteins was determined using multiplex serology, an antibody detection method based on a glutathione S-transferase capture assay in combination with fluorescent bead technology.16–19 This assay is highly rigorous and reproducible; an analysis of serum samples from 114 OPSCC patients found an intra-individual correlation of 1.0 for HPV16 E6 seropositivity.7 Antibody levels were quantified as median fluorescence intensity (MFI) and dichotomized (positive/negative) based on the following defined cut points.7,20 For HPV16 E6, two mutually exclusive categories of HPV16 E6 seroreactivity were created: (i) moderate: MFI ≥ 484 and < 1,000; and high: MFI ≥1,000. Previous work showed that increasing the seropositivity cutoff of HPV16 E6 from 484 to 1,000 resulted in an increased specificity for OPSCC without an associated decrease in sensitivity.21 For the other HPV16 proteins, the MFI cutoffs used to define seropositivity were: L1, 422; E1, 200; E2, 679; E4, 876; E7, 548. For the E6 proteins of non-HPV16 types, the MFI cutoffs for seropositivity were: HPV6, 500; HPV11, 260; HPV18, 243; HPV31, 890; HPV33, 253; HPV35, 260; HPV45, 249; HPV52, 271.21 These cutoffs are based on Clifford et al22 and were calculated as the mean plus five standard deviations of 117 DNA negative, female self-reported virgins. These cutoffs have remained the same and have been used in many publications, with the exception of HPV16 E6. The cutoff for HPV16 E6 was raised from 484 to 1000 MFI to improve specificity in HPV+OPSCC patients who were at or very close to diagnosis; however, 484 MFI is still used for the healthy screening population prior to an OPSCC diagnosis.
Clinical Variables
Demographic and clinical variables corresponding to the time of blood collection were retrieved from the TN-CFAR biorepository and through medical chart review. The following variables were included in this analysis: age at blood collection, race (Black, White, Other), HIV acquisition risk factors (men that have sex with men [MSM]), heterosexual, injection drug use, and other), years living with HIV (calculated based on the age at blood collection minus the age of HIV diagnosis) and nadir CD4+ T-cell count (cells/mm3). We recognize other factors such as anal HSIL or cancer can cause increased HPV16 E6, but because this study was only funded for OPSCC, other data regarding anal HSIL or cancer was not collected.
Statistical Analyses
Descriptive statistics were used to summarize the demographic (age at blood draw, race) and clinical characteristics (HIV risk factors, nadir CD4+ T-cell count, years living with HIV) of the participants. Ethnicity was excluded as 78% of participants had missing information. Seroprevalence of HPV16 antibodies was calculated for all HPV16 proteins analyzed (L1, E1, E2, E4, E6, E7). Demographic, clinical and serologic determinants of moderate and high HPV16 E6 seropositivity were evaluated using univariable and multivariable logistic regression; odds ratios (OR) and 95% confidence intervals (CI) were calculated. The multivariable logistic regression included only participants with complete data, making this analysis a complete case analysis. Serologic variables evaluated included seroreactivity against: (i) other HPV16 proteins (L1, E1, E2, E4, and E7) and (ii) seropositivity against multiple HPV16 E antigens. All analyses were performed by Stata version 18.0.126 (RRID:SCR_012763).
Data Availability
Data that support this study are only available upon requests. They are not publicly accessible due to the delicate nature of the data presented in this study. Data requests can be directed to the Tennessee Center for AIDS Research (tn-cfar@vumc.org).
RESULTS
Participant Characteristics
A total of 2,320 men living with HIV with HPV serologic testing results were included in the analysis, of which 1,643 (71%) had full demographic and clinical information available. Median age at blood collection was 50 years (interquartile range [IQR]: 43 to 56 years). The majority were White, reported sex with men (MSM) as the main HIV risk factor and were living with HIV for more than 5 years at the time of blood draw. Over 40% of the total sample had a documented nadir absolute CD4+ T-cell count less than 200 cells/mm3 (Table 1).
Table 1.
Participant Characteristics (N=2,320)
| Characteristics | N (%) |
|---|---|
| Median age at blood collection (interquartile range, IQR) | 50 (43 to 56) |
| Age at blood collection | |
| ≤40 | 400 (17.24) |
| 40+ | 1,914 (82.50) |
| Missing | 6 (0.26) |
| Race | |
| White | 1,568 (67.59) |
| Black | 665 (28.66) |
| Other | 48 (2.07) |
| Missing | 39 (1.68) |
| HIV acquisition risk factor | |
| Men that have sex with men (MSM) | 1,207 (52.03) |
| Heterosexual | 285 (12.28) |
| Injection Drug Use | 166 (7.16) |
| Other | 23 (0.99) |
| Missing | 639 (27.54) |
| Nadir CD4+ T-cell count, cells/mm3 | |
| ≤200 | 968 (41.72) |
| 200+ | 755 (32.54) |
| Missing | 597 (25.73) |
| Years with HIV | |
| Less than 5 | 294 (12.67) |
| ≥5 and <10 | 378 (16.29) |
| ≥10 and <15 | 392 (16.90) |
| ≥15 and <20 | 350 (15.09) |
| 20+ | 295 (12.72) |
| Missing | 611 (26.34) |
Seroprevalence of HPV Antibodies Among Participants
One hundred and thirty men (5.6%) were HPV16 E6 seropositive; of which 55 (2.4%) had moderate antibody levels and 75 (3.2%) had high levels. Seroreactivity against HPV16 L1 was most common (22.8%), followed by HPV16 E4 (10.5%), HPV16 E6 (5.6%), HPV16 E2 (4.8%), and HPV16 E7 (4%). Seroreactivity against E6 proteins from other high-risk HPV types (HPV18, HPV33 and HPV45) was relatively rare and ranged from 2.1% to 2.6%, (Table 2). Please see Supplementary Table S1 for additional data regarding seroprevalence of HPV antibodies.
Table 2.
Seroprevalence of HPV antibodies (N= 2,320)
| HPV Proteins | No. Positive (%) |
|---|---|
| HPV16 Proteins | |
| HPV16 E6 overall | 130 (5.60) |
| HPV16 E6 moderate | 55 (2.37) |
| HPV16 E6 high | 75 (3.23) |
| HPV16 L1 | 530 (22.84) |
| HPV16 E1 | 70 (3.02) |
| HPV16 E2 | 112 (4.83) |
| HPV16 E4 | 244 (10.54) |
| HPV16 E7 | 92 (3.97) |
| Non-HPV16 Types | |
| HPV18 E6 | 48 (2.07) |
| HPV33 E6 | 61 (2.63) |
| HPV45 E6 | 58 (2.50) |
Six participants were missing data on HPV16 E4 seropositivity status
Serologic and Clinical Determinants of HPV16 E6 Seropositivity
HPV16 E6 seropositive men were significantly more likely to be seroreactive against at least 1 additional HPV16 protein compared with HPV16 E6 seronegative men; 56.2% versus 35.9%, respectively (OR: 2.29 [95% CI: 1.60-3.27]; P<0.001), Table 3. Compared with HPV16 E6 seronegatives, HPV16 E6 seropositive men were significantly more likely to be seroreactive against L1 (OR: 2.47 [95% CI: 1.71-3.56]; P<0.001); and E2 (OR: 4.15 [95% CI: 2.46-6.98]; P<0.001). HPV16 E6 seropositive men were also significantly more likely to be seroreactive against multiple HPV16 E proteins; OR: 1.67 (95% CI: 1.10-2.52; P=0.015) for seroreactivity against one additional HPV16 E proteins; OR: 3.21 (95% CI: 1.40-7.33; P=0.006) for seroreactivity against two additional HPV16 E proteins, (Table 3). No significant associations were observed between HPV16 E6 seropositivity and age, race, HIV risk factors, nadir CD4+ T-cell counts or years living with HIV in the multivariable logistic regression analysis (Table 4).
Table 3.
Association between HPV16 E6 seropositivity and other HPV16 antibodies
| HPV16 E6 Seronegative |
HPV16 E6 Seropositive |
||||||
|---|---|---|---|---|---|---|---|
| HPV16 Proteins | Total | No. Positive (%) | OR | Total | No. Positive (%) | OR (95% CI) | P-Value |
| Any1 | 2,184 | 35.90 | Ref | 130 | 56.15 | 2.29 (1.60-3.27) | <0.001 |
| HPV16 L1 | 2,190 | 21.78 | Ref | 130 | 40.77 | 2.47 (1.71-3.56) | <0.001 |
| HPV16 E1 | 2,190 | 2.97 | Ref | 130 | 3.85 | 1.31 (0.52-3.31) | 0.571 |
| HPV16 E2 | 2,190 | 4.20 | Ref | 130 | 15.38 | 4.15 (2.46-6.98) | <0.001 |
| HPV16 E4 | 2,184 | 10.53 | Ref | 130 | 10.77 | 1.03 (0.58-1.82) | 0.932 |
| HPV16 E7 | 2,190 | 3.84 | Ref | 130 | 6.15 | 1.64 (0.78-3.47) | 0.193 |
| Positive for 1 additional E antigen1 | 2,143 | 18.01 | Ref | 123 | 26.83 | 1.67 (1.10-2.52) | 0.015 |
| Positive for 2 additional E antigens1 | 2,181 | 1.74 | Ref | 130 | 5.38 | 3.21 (1.40-7.33) | 0.006 |
| Positive for 3 additional E antigens1 | 2,184 | 0.14 | Ref | 130 | 0.00 | NE | - |
In addition to HPV16 E6.
Table 4.
Multivariable logistic regression results for the association between HPV16 E6 seropositivity and demographic and clinical characteristics (N=1,643).
| Seronegative (N= 1,569) |
Seropositive (N= 74) |
|||||
|---|---|---|---|---|---|---|
| Characteristics | N | % | N | % | aOR1 (95% CI) | P-value |
| Age at blood collection | ||||||
| Median (IQR) | 49.57 | 42.70, 55.53 | 49.47 | 42.22, 58.57 | 1.01 (0.99-1.04) | 0.280 |
| Race | ||||||
| White | 1,040 | 66.28 | 50 | 67.57 | Ref | NE |
| Black | 500 | 31.87 | 23 | 31.08 | 0.94 (0.55-1.62) | 0.382 |
| Other | 29 | 1.85 | 1 | 1.35 | 0.74 (0.10-5.56) | 0.768 |
| HIV acquisition risk factor | ||||||
| Men that have sex with men (MSM) | 1,122 | 71.51 | 55 | 74.32 | Ref | NE |
| Heterosexual | 264 | 16.83 | 15 | 20.27 | 1.15 (0.61-2.16) | 0.674 |
| Injection Drug Use | 160 | 10.20 | 4 | 5.41 | 0.50 (0.18-1.42) | 0.194 |
| Other | 23 | 1.47 | 0 | 0.0 | NE | NE |
| Nadir CD4+ T-cell count, cells/mm3 | ||||||
| ≤200 | 889 | 56.47 | 42 | 56.58 | Ref | NE |
| >200 | 683 | 43.53 | 32 | 43.42 | 1.00 (0.62-1.61) | 0.992 |
| Years with HIV | ||||||
| Median (IQR) | 12.66 | 7.18, 18.01 | 11.91 | 5.86, 20.09 | 1.00 (0.82-1.21) | 0.808 |
All variables in the table were included in the model to calculate adjusted odds ratios (aOR); 1,643 subjects had complete information on the variates in the table and were used to fit the multivariable model.
DISCUSSION
Among the 2,320 participants evaluated, overall HPV16 E6 seroprevalence was nearly 6% -- considerably higher than prior reports in the general male population.8,9,23 HPV16 L1 antibodies, a marker of past HPV exposure,7 was most commonly detected with nearly a quarter of participants testing positive and was consistent with prior studies among men with HIV, where seroprevalence ranged from 32% to 37%.11,13 HPV16 E4 antibodies were the second most common, followed by HPV16 E6 and HPV16 E2 antibodies. HPV16 E6 seropositivity was strongly associated with seroreactivity against other HPV16 proteins. Nearly 60% of HPV16 E6 seropositive men were seroreactive against at least one other HPV16 protein and over 5% were seroreactive against 2 or more HPV16 E proteins compared with 36% and 2% of HPV16 E6 seronegatives, respectively. HPV16 E6 seropositivity, particularly when associated with seroreactivity against additional early HPV16 proteins, has been strongly associated with HPV+OPSCC development.24 HPV16 E6 seropositivity has been shown to be a potentially reliable indicator of OPSCC, some studies show a sensitivity of 95% and a specificity of 100%.24 Interestingly, this study also reported that HPV16 E6 antibodies were the most prevalent antibody in OPSCC cases, followed by E2, E7 and E1.24 Due to the fact HPV16 E6 seropositivity is quite rare, less than 1% in the healthy population24, it is important to find the populations most at risk so screening efforts can be focused appropriately. While we did not observe an association between HPV16 E6 seropositivity and clinical and demographic factors, we acknowledge that we may have been underpowered to detect associations due to missing data.
To our knowledge, only six prior studies have examined HPV16 E6 serology among people living with HIV; five among men11–15 and one among women.10 Prior studies of similarly aged men living with HIV ranged in size from 248 to 1,447 and reported HPV16 E6 seroprevalences that ranged from 1.1% to 3.2%.11–15 HPV16 E6 seroprevalence estimates reported in these prior studies were considerably lower than observed in our study, which found that nearly 6% of participants tested had detectable HPV16 E6 antibodies. While all prior studies used the same HPV multiple serology assay16–19, one possible explanation for the difference in seroprevalence estimates may have been the MFI cutoffs used to define seropositivity. Among the three studies that used a 484 MFI cutoff, HPV16 E6 seroprevalence ranged 1.1% to 2.5%,12,14,15 while the two studies that used a 1,000 MFI cutoff ranged from 1.1% to 3.2%.11,13 To improve our ability to compare our results to prior studies, we calculated HPV16 E6 seroprevalence using both MFI cutoffs. When using the more stringent cutoff of 1,000 MFI, our HPV16 E6 seroprevalence was 3.23%, which still exceeded the seroprevalence estimate of all but one of the previously mentioned studies and suggests these differences are not solely due to differences in MFI cutoffs. Given that HPV16 E6 seropositivity is a marker of OPSCC risk, seroprevalence would be expected to be higher in regions with elevated incidence of OPSCC; and thus, this is a likely explanation for the high HPV16 E6 seroprevalence observed in our population. Only two prior studies were conducted in the United States11,12 and none included participants from the southeast region. In contrast, our study took place in Tennessee, located within the southeastern region of the US where OPSCC rates are the highest in the country.25 As of 2022, 32% of all OPSCCs in the US were diagnosed in the southeastern states.25 While the reasons underlying the high incidence of OPSCC in the southeast are currently unknown, the southeastern US has the poorest health outcomes in the country with increased tobacco use, high HIV prevalence, low HPV vaccination rates, and poor access to care.26,27
To better understand which subpopulations were most likely to be HPV16 E6 seropositive, we evaluated the association of HPV16 E6 seropositivity with several demographic and clinical factors. Similar to the prior study by Combes et al.,15 we did not observe any significant associations between HPV16 E6 seropositivity and the clinical and demographic factors evaluated. This includes the lack of association between HPV16 E6 seropositivity and CD4 nadir in our study and in the study by Combes, et al. While ART has been shown to reduce the risk of cervical cancer28, it could also potentially reduce the risk of anal and HPV+OPSCC.29,30 However, we and others have shown that even with immune reconstitution, PWH are at increased risk for other HPV-driven cancers due to altered immunity likely driven by chronic immune activation and immunosenescence even after adjusting for CD4 count.31 Both Zhang et al. and D’Souza et al. reported increased odds of HPV16 E6 seropositivity with older age.11,12 It is possible that HPV16 E6 seropositivity increases with age due to repeated exposure or inability to clear the virus, but other factors like altered immunity through low CD4 nadir are needed to drive carcinogenesis. Interestingly, a large study among nearly 10,000 individuals without HIV found sexual behaviors to be the strongest predictor of HPV16 E6 seropositivity.32 Detailed, reliable information about sexual behavior at the time of specimen collection was not available for our study, which used retrospective data collected as part of routine clinical care.
One of the limitations of our study was the restricted number of variables present in the dataset and the percentage of individuals with missing data. While the TN-CFAR collects and banks research blood samples from all participants who consent to repository research, clinical variables were only automatically collected for participants who attended two primary care visits within one year, suggesting that the group of participants with missing data were likely not regularly attending the clinic. These individuals may constitute a higher-risk group as we observed an increased HPV16 E6 seroprevalence among this group with missing clinical information (9.1% vs. 4.4%). Additionally, we did not find significant associations between HPV16 E6 seropositivity and any of the demographic and clinical factors evaluated, as we were likely underpowered due to the percentage of missing data.
This study is nested within a larger study where we are reviewing charts and calling back all seropositives. While outside the scope of this study, we are actively conducting a chart review to ascertain which participants went on to develop HPV-associated cancers. Additionally, our study population included only patients with a history of receiving care at Vanderbilt University Medical Center; thus, our results are not generalizable to the full population of men living with HIV. While our results are not directly generalizable to the full population of men living with HIV in the southeast, we tested every available sample in the TN-CFAR biorepository in an effort to reduce selection bias. We are unable to obtain the data to compare our demographics to the demographics of the population of men living with HIV, however, we did test every available sample in the biorepository in an effort to reduce selection bias. Despite these limitations, our findings fill an important knowledge gap, given that our study is the first study to evaluate HPV antibodies in PWH in the Southeastern United States, the region with the highest prevalence of both HIV and HPV+OPSCC in the nation.25 While we do not know the cancer status of the seropositive individuals we studied, we are currently following up with them and screening for OPSCC. Additionally, we have several ongoing retrospective and prospective studies that examine HPV16 E6 seropositivity in relation to diagnosis of OPSCC.
In conclusion, this study offers important information on the seroprevalence of HPV antibodies among men living with HIV in the Southeastern US. Given that HPV+OPSCC is considered a rare cancer nationally, it is important to identify populations with high HPV16 E6 seroprevalence that would allow for future studies to be sufficiently powered to evaluate HPV16 E6 seropositivity as a potential tool for early detection. Additionally, given the geographic variation in OPSCC incidence, these studies should be conducted in the populations most likely to benefit from OPSCC screening to ensure health equity. While results from phase two of the HIV-ENDEAVOR study will provide important data regarding the utility of the HPV16 E6 antibodies for early detection of HPV+OPSCC in PWH, additional studies are needed to gain a better understanding of HPV serology in the population of people living with HIV, particularly in the regions like the southeastern US where HIV and HPV+OPSCC incidence is especially high and increasing.25
Supplementary Material
Prevention Relevance Statement:
Our findings fill an important gap, given that our study is the largest to date to evaluate HPV antibodies among men living with HIV and is the first study to do so in the Southeastern US, the region with the highest prevalence of both HIV and HPV+OPSCC in the nation.
Funding Information
This work was supported by funding from the National Institutes of Health, National Institute of Dental and Craniofacial Research (R01DE029650; PI: K.A. Lang Kuhs) and was funded in part by the NIH-funded Tennessee Center for AIDS Research (P30 AI110527; PI: J. Koethe) and NIH CTSA (UL1TR001998; PI: P.A. Kern).
Footnotes
Conflict of Interest
TW serves on advisory boards for Merck (MSD) Sharp & Dohme. S.L. Sudenga and T. Waterboer report personal fees from Merck outside the submitted work. The other authors have no conflicts of interest to declare.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
Data that support this study are only available upon requests. They are not publicly accessible due to the delicate nature of the data presented in this study. Data requests can be directed to the Tennessee Center for AIDS Research (tn-cfar@vumc.org).