Skip to main content

Advertisement

SpringerLink
Log in

Do immune inflammatory markers correlate with anal dysplasia and anal cancer risk in patients living with HIV?

  • Original Article
  • Published:
International Journal of Colorectal Disease Aims and scope Submit manuscript

Abstract

Purpose

People living with HIV (PLWH) are at an elevated risk for developing anal cancer. As screening is invasive, markers predicting those at highest risk for anal cancer could guide individualized screening. Neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), and prognostic nutritional index (PNI) are surrogate inflammatory/immune markers known to correlate with cancer outcomes. This study aims to assess whether these markers correlate with anal cancer risk in PLWH.

Methods

This is a retrospective single-institution cohort study of PLWH at a single academic medical center who were diagnosed with or screened for anal dysplasia between 2001 and 2019. Aforementioned markers collected within one year of diagnosis were recorded. Regression modeling was used to estimate odds of anal cancer. Receiver operating characteristic analysis was utilized to determine optimal cutoff for screening values.

Results

Five-hundred-fourteen patients were included. NLR and PNI were significantly associated with cancer risk on univariate (p = 0.03, p = 0.001) and multivariate analyses (p = 0.03, p = 0.01). NLR increased across all grades of dysplasia. PLR was not associated with cancer risk. A NLR of ≥ 1.64 can be utilized to capture 76% of cancer patients in our cohort.

Conclusions

NLR values in patients living with HIV correlate with risk of anal cancer and increasing grades of dysplasia. A cutoff NLR of ≥ 1.64 can be used to help capture those at risk. NLR is a promising marker of risk of anal cancer and progression of anal dysplasia in patients with HIV infection and could be used to risk-stratify screening and surveillance intervals.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Ryan DP, Compton CC, Mayer RJ (2000) Carcinoma of the anal canal. N Engl J Med 342:792–800. https://doi.org/10.1056/NEJM200003163421107

    Article  CAS  PubMed  Google Scholar 

  2. Koskan AM, Brennhofer SA, Helitzer DL (2019) Screening for anal cancer precursors among patients living with HIV in the absence of national guidelines: practitioners’ perspectives. Cancer Causes Control 30:989–996. https://doi.org/10.1007/s10552-019-01209-8

    Article  PubMed  Google Scholar 

  3. Apaydin KZ, Fontenot HB, Shtasel DL, Mayer KH, Keuroghlian AS (2018) Primary care provider practices and perceptions regarding HPV vaccination and anal cancer screening at a boston community health center. J Community Health 43:792–801. https://doi.org/10.1007/s10900-018-0486-0

    Article  PubMed  PubMed Central  Google Scholar 

  4. Templeton AJ, McNamara MG, Šeruga B et al (2014) Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors: a systematic review and meta-analysis. J Natl Cancer Inst 106:dju124. https://doi.org/10.1093/jnci/dju124

  5. Sun K, Chen S, Xu J, Li G, He Y (2014) The prognostic significance of the prognostic nutritional index in cancer: a systematic review and meta-analysis. J Cancer Res Clin Oncol 140:1537–1549. https://doi.org/10.1007/s00432-014-1714-3

    Article  PubMed  Google Scholar 

  6. Casadei-Gardini A, Montagnani F, Casadei C et al (2019) Immune inflammation indicators in anal cancer patients treated with concurrent chemoradiation: training and validation cohort with online calculator (ARC: Anal Cancer Response Classifier). Cancer Manag Res 11:3631–3642. https://doi.org/10.2147/CMAR.S197349

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. De Felice F, Rubini FL, Romano L et al (2019) Prognostic significance of inflammatory-related parameters in patients with anal canal cancer. Int J Colorectal Dis 34:519–525. https://doi.org/10.1007/s00384-018-03225-7

    Article  PubMed  Google Scholar 

  8. Schernberg A, Escande A, Rivin Del Campo E et al (2017) Leukocytosis and neutrophilia predicts outcome in anal cancer. Radiother Oncol 122:137–145. https://doi.org/10.1016/j.radonc.2016.12.009

    Article  PubMed  Google Scholar 

  9. Toh E, Wilson J, Sebag-Montefiore D, Botterill I (2014) Neutrophil:lymphocyte ratio as a simple and novel biomarker for prediction of locoregional recurrence after chemoradiotherapy for squamous cell carcinoma of the anus. Colorectal Dis 16:O90–O97. https://doi.org/10.1111/codi.12467

    Article  CAS  PubMed  Google Scholar 

  10. Knight K, Choong JX, McKee RF et al (2021) The influence of systemic inflammation on treatment response and survival in anal squamous cell cancer. Clin Oncol (R Coll Radiol) 33:e22–e30. https://doi.org/10.1016/j.clon.2020.06.010

  11. Campos VJ, Mazzini GS, Juchem JF, Gurski RR (2020) Neutrophil-lymphocyte ratio as a marker of progression from non-dysplastic Barrett’s esophagus to esophageal adenocarcinoma: a cross-sectional retrospective study. J Gastrointest Surg 24:8–18. https://doi.org/10.1007/s11605-019-04456-x

    Article  PubMed  Google Scholar 

  12. Quiros-Roldan E, Raffetti E, Donato F et al (2016) Neutrophil to lymphocyte ratio and cardiovascular disease incidence in HIV-infected patients: a population-based cohort study. PLoS One 11:e0154900. https://doi.org/10.1371/journal.pone.0154900

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Duman TT, Aktas G, Atak BM, Kocak MZ, Erkus E, Savli H (2019) Neutrophil to lymphocyte ratio as an indicative of diabetic control level in type 2 diabetes mellitus. Afr Health Sci 19:1602–1606. https://doi.org/10.4314/ahs.v19i1.35

    Article  PubMed  PubMed Central  Google Scholar 

  14. Machalek DA, Poynten M, Jin F et al (2012) Anal human papillomavirus infection and associated neoplastic lesions in men who have sex with men: a systematic review and meta-analysis. Lancet Oncol 13:487–500. https://doi.org/10.1016/S1470-2045(12)70080-3

    Article  PubMed  Google Scholar 

  15. Durante AJ, Williams AB, Da Costa M, Darragh TM, Khoshnood K (2003) Palefsky JM (2003) Incidence of anal cytological abnormalities in a cohort of human immunodeficiency virus-infected women. Cancer Epidemiol Biomarkers Prev 12:638–642

    PubMed  Google Scholar 

  16. Schim van der Loeff MF, Mooij SH, Richel O, de Vries HJC, Prins JM (2014) HPV and anal cancer in HIV-infected individuals: a review. Curr HIV/AIDS Rep 11:250–262. https://doi.org/10.1007/s11904-014-0224-x

    Article  PubMed  Google Scholar 

  17. Bedimo RJ, McGinnis KA, Dunlap M, Rodriguez-Barradas MC, Justice AC (2009) Incidence of non-AIDS-defining malignancies in HIV-infected versus noninfected patients in the HAART era: impact of immunosuppression. J Acquir Immune Defic Syndr 52:203–208. https://doi.org/10.1097/QAI.0b013e3181b033ab

    Article  PubMed  PubMed Central  Google Scholar 

  18. Chaturvedi AK, Madeleine MM, Biggar RJ, Engels EA (2009) Risk of human papillomavirus-associated cancers among persons with AIDS. J Natl Cancer Inst 101:1120–1130. https://doi.org/10.1093/jnci/djp205

    Article  PubMed  PubMed Central  Google Scholar 

  19. Vanhaesebrouck A, Pernot S, Pavie J et al (2020) Factors associated with anal cancer screening uptake in men who have sex with men living with HIV: a cross-sectional study. Eur J Cancer Prev 29:1–6. https://doi.org/10.1097/CEJ.0000000000000507

    Article  PubMed  Google Scholar 

  20. Apaydin KZ, Nguyen A, Borba CPC et al (2019) Factors associated with anal cancer screening follow-up by high-resolution anoscopy. Sex Transm Infect 95:83–86. https://doi.org/10.1136/sextrans-2017-053515

    Article  PubMed  Google Scholar 

  21. Wells JS, Holstad MM, Watkins BD (2018) Sociodemographic predictors of anal cancer screening and follow-up in human immunodeficiency virus-infected individuals. Cancer Nurs 41:424–430. https://doi.org/10.1097/NCC.0000000000000524

    Article  PubMed  PubMed Central  Google Scholar 

  22. Yanik EL, Napravnik S, Cole SR, Incidence and timing of cancer in HIV-infected individuals following initiation of combination antiretroviral therapy, et al (2013) Clin Infect Dis 57:756–764. https://doi.org/10.1093/cid/cit369

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Colón-López V, Shiels MS, Machin M et al (2018) Anal cancer risk among people with HIV infection in the United States. J Clin Oncol 36:68–75. https://doi.org/10.1200/JCO.2017.74.9291

    Article  PubMed  Google Scholar 

  24. Geltzeiler CB, Xu Y, Carchman E et al (2020) CD4/CD8 ratio as a novel marker for increased risk of high-grade anal dysplasia and anal cancer in HIV+ patients: a retrospective cohort study. Dis Colon Rectum 63:1585–1592. https://doi.org/10.1097/DCR.0000000000001763

    Article  PubMed  Google Scholar 

  25. Gonçalves JCN, Macedo ACL, Madeira K et al (2019) Accuracy of anal cytology for diagnostic of precursor lesions of anal cancer: systematic review and meta-analysis. Dis Colon Rectum 62:112–120. https://doi.org/10.1097/DCR.0000000000001231

    Article  PubMed  Google Scholar 

  26. Basim P, Yuksel M (2020) Peripheral inflammatory biomarkers as predictors of recurrence in surgically-treated anogenital condylomata acuminata patients. Int J STD AIDS 31:1380–1388. https://journals.sagepub.com/doi/10.1177/0956462420950562

Download references

Acknowledgements

The authors would like to acknowledge Linda Cherney-Stafford for her contributions via data collection. This work was presented at the American Society of Colon and Rectal Surgeons Annual Scientific Meeting, Podium Presentation April, 2021.

Author information

Authors and Affiliations

  1. Department of Surgery, University of North Carolina at Chapel Hill School of Medicine, Campus Box 7081, Chapel Hill, NC, 27599-7211, USA

    Jonathan Stem

  2. Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA

    Qiuyu Yang, Evie Carchman & Cristina B. Sanger

  3. William S. Middleton Memorial Veteran’s Hospital, Madison, WI, USA

    Evie Carchman, Robert Striker & Cristina B. Sanger

  4. Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA

    Robert Striker

Authors
  1. Jonathan Stem
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Qiuyu Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Evie Carchman
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Robert Striker
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Cristina B. Sanger
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conception and design: J. S., E. C., R. S., C. S. Analysis and interpretation: J. S., Q. Y., E. C., R. S., C. S. Drafting and revision: J. S., Q. Y., E. C., R. S., C. S.

Corresponding author

Correspondence to Jonathan Stem.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Stem, J., Yang, Q., Carchman, E. et al. Do immune inflammatory markers correlate with anal dysplasia and anal cancer risk in patients living with HIV?. Int J Colorectal Dis 37, 983–988 (2022). https://doi.org/10.1007/s00384-022-04123-9

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00384-022-04123-9

Keywords

Search

Navigation