Women with HIV are more likely to develop cervical cancer: Why?

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HIV & cervical cancer

Women with HIV are more likely to develop cervical cancer: Why?

Cervical cancer screening is low in many areas: 

Over the years, through screening and vaccination, cervical cancer incidence as well as mortality rates have declined in many high-income countries. Yet, every year, more than 260,000 women die due to the disease, out of which, almost 90% occur in low- and middle-income regions, including areas of Africa, Asia, Latin America and the Caribbean (1). Primary reasons for the disparity include poor screening and vaccination uptake in these areas.  

 

HIV HPV figure 1_V2.png

 

HIV positive women are more likely to develop cervical cancer:  

It is well-established that high-risk human papillomavirus (hrHPV) strains are a major contributor to cervical cancer (1). While most HPV infections cause no harm and disappear naturally overtime in healthy individuals, women with compromised immune conditions such as Human immunodeficiency virus (HIV), are more likely to develop persistent HPV infections (1,2). This can cause cervical abnormalities, which if left untreated, can lead to invasive cervical cancer (1).  

 

HIV HPV figure 2_V3.png

 

Further, in HIV-positive patients, HPV-related tumors tend to occur at a younger age and at a more advanced stage, highlighting the poor clearance of HPV infections in those infected with HIV (3)

Given the synergy between the two infections, it is critical that women with HIV are screened regularly for HPV. Guidelines by the World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC) recommend that newly diagnosed HIV-positive women undergo their first cervical cancer screening session at the time they receive their HIV health status and are sexually active (1,2). A repeat test is recommended after 6 or 12 months. Later, routine screening can be scheduled every 3 years, after three consecutive negative results. For women older than 30, with abnormal cytology or HPV test results, additional measures such as colposcopy and biopsies may be required (2)

Importance of screening and potential of urine as a sample type: 

To reduce preventable cervical cancer deaths, the WHO recommends methods to increase awareness through health education and improve HPV vaccination and cervical cancer screening uptake (1). Cytology-based Pap smears are the traditional screening approach, which look for abnormal cervical cells. Despite the benefits, many women are often reluctant to undergo a Pap smear as the procedure is invasive and associated with physical discomfort. Additionally, religion, culture, inconvenient clinic hours, and/or lack of transportation can also influence decision of testing (4,5). 

Therefore, improving screening uptake is necessary. Most low- and middle-income countries, which have the most women living with HIV, also have limited programs for cervical cancer prevention and control (1). For example, screening and HPV vaccination rates are considering low in women living with HIV (6). In this population especially, alternative methods are critical. 

HIV HPV figure 3_V3.png

HPV testing on self-collected samples is becoming increasingly acceptable and can be used as an additional strategy to reach women who do not participate in regular screening programs (7). HPV can be detected in urine (8) and offers several benefits.   

Women have shown a significantly higher preference to urine as a sample type for hrHPV testing in comparison to brush-based cervical-vaginal self-sampling methods (9,10). Urine is also preferred as it non-invasive and suitable for home-collection (9,11). Recent studies confirm similar sensitivities between urine and clinician-taken smears as well as brush-based self-sampling for detecting high-grade lesions, (8,11), further highlighting the potential of urine as a sample type. 

To know more urine as a preferred sample type for HPV detection, read our blog.

Colli-Pee® - An innovative urine collection solution: 

First-void urine (initial urine flow) contains higher concentrations of HPV DNA than a midstream urine sample (12,13), which is necessary for improved diagnostic accuracy. For this reason, Novosanis developed Colli-Pee®, a urine collection device, which allows for standardized, volumetric collection of first-void urine. Additionally, for HPV testing, a urine preservative is recommended to improve stability of the sample. Colli-Pee® can be pre-filled with Novosanis non-toxic proprietary Urine Conservation Medium (UCM).  

To know more  about Colli-Pee® in HPV-based cervical cancer screening read our white paper.

To know more on the journey of Colli-Pee read our white paper.

Conclusion: 

As women living with HIV are more at risk to develop invasive cervical cancer, regular screening for the cancer type is even more critical in this population. HIV rates in adolescent girls and young women are particularly high in areas where cervical cancer screening is significantly low. In these regions, that that have poor access to essential health services, urine as a sample type for HPV detection offers great potential to reach more women, especially those living with HIV. 

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References:  
(1) HPV, HIV and cervical cancer - Leveraging synergies to save women’s lives. UNAIDS. 2016; https://www.unaids.org/sites/default/files/media_asset/JC2851_HPV-HIV-cervicalcancer_en.pdf 
(2) Ghebre RG, Grover S, Xu MJ, Chuang LT, Simonds H. Cervical cancer control in HIV-infected women: Past, present and future. Gynecol Oncol Rep. 2017 Jul 21;21:101-108. doi: 10.1016/j.gore.2017.07.009. PMID: 28819634; PMCID: PMC5548335. 
(3) Brianti P, De Flammineis E, Mercuri SR. Review of HPV-related diseases and cancers. New Microbiol. 2017 Apr;40(2):80-85. Epub 2017 Apr 3. PMID: 28368072. 
(4) Racey CS, Withrow DR, Gesink D. Self-collected HPV testing improves participation in cervical cancer screening: a systematic review and meta-analysis. Can J Public Health. 2013 Feb 11;104(2):e159-66. Review. PubMed PMID: 23618210; PubMed Central PMCID: PMC6973997. 
(5) Sarah Wilding , Sarah Wighton , Daisy Halligan , Robert West , Mark Conner & Daryl B. O’Connor (2020) What factors are most influential in increasing cervical cancer screening attendance? An online study of UK-based women1 , Health Psychology and Behavioral Medicine,8:1, 314-328, DOI: 10.1080/21642850.2020.1798239 
(6) Valanikas E, Dinas K, Tziomalos K. Cancer prevention in patients with human immunodeficiency virus infection. World J Clin Oncol. 2018 Sep 14;9(5):71-73. doi: 10.5306/wjco.v9.i5.71. PMID: 30254961; PMCID: PMC6153129. 
(7) Arbyn M, Peeters E, Benoy I, Vanden Broeck D, Bogers J, De Sutter P, Donders G, Tjalma W, Weyers S, Cuschieri K, Poljak M, Bonde J, Cocuzza C, Zhao FH, Van Keer S, Vorsters A. VALHUDES: A protocol for validation of human papillomavirus assays and collection devices for HPV testing on self-samples and urine samples. J Clin Virol. 2018 Oct;107:52-56. doi: 10.1016/j.jcv.2018.08.006. Epub 2018 Aug 22. PubMed PMID: 30195193. 
(8) Fontenot HB. Urine-based HPV testing as a method to screen for cervical cancer. Nurs Womens Health. 2015 Feb-Mar;19(1):59-65. doi: 10.1111/1751-486X.12176. PMID: 25690816. 
(9) Van Keer S, Pattyn J, Tjalma WAA, Van Ostade X, Ieven M, Van Damme P, Vorsters A. First-void urine: A potential biomarker source for triage of high-risk human papillomavirus infected women. Eur J Obstet Gynecol Reprod Biol. 2017 Sep;216:1-11. doi: 10.1016/j.ejogrb.2017.06.036. Epub 2017 Jun 27. Review. PubMed PMID: 28689156. 
(10) Rohner E, McGuire FH, Liu Y, Li Q, Miele K, Desai SA, Schmitt JW, Knittel A, Nelson JAE, Edelman C, Sivaraman V, Baker A, Romocki LS, Rahangdale L, Smith JS. Racial and Ethnic Differences in Acceptability of Urine and Cervico-Vaginal Sample Self-Collection for HPVBased Cervical Cancer Screening. J Womens Health (Larchmt). 2020 Jul;29(7):971-979. doi: 10.1089/jwh.2019.8132. Epub 2020 Mar 26. PubMed PMID: 32212991; PubMed Central PMCID: PMC7371548. 
(11) Leeman A, Del Pino M, Molijn A, Rodriguez A, Torné A, de Koning M, Ordi J, van Kemenade F, Jenkins D, Quint W. HPV testing in firstvoid urine provides sensitivity for CIN2+ detection comparable with a smear taken by a clinician or a brush-based self-sample: crosssectional data from a triage population. BJOG. 2017 Aug;124(9):1356-1363. doi: 10.1111/1471-0528.14682. PubMed PMID: 28391609. 
(12) Vorsters A, Van den Bergh J, Micalessi I, Biesmans S, Bogers J, Hens A, De Coster I, Ieven M, Van Damme P. Optimization of HPV DNA detection in urine by improving collection, storage, and extraction. Eur J Clin Microbiol Infect Dis. 2014 Nov;33(11):2005-14. doi: 10.1007/s10096-014-2147-2. Epub 2014 Jun 12. PubMed PMID: 24916950. 
(13)  Pattyn J, Van Keer S, Biesmans S, Ieven M, Vanderborght C, Beyers K, Vankerckhoven V, Bruyndonckx R, Van Damme P, Vorsters A. Human papillomavirus detection in urine: Effect of a first-void urine collection device and timing of collection. J Virol Methods. 2019 Feb;264:23-30. doi: 10.1016/j.jviromet.2018.11.008. Epub 2018 Nov 16. PubMed PMID: 30452931.