HPV and Vitamin D - several studies

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HPV warts treated by both Intralesional and topical Vitamin D - March 2024

Vitamin D and HPV infection: Clinical pearls
J Cosmet Dermatol. 2024 Mar 15. doi: 10.1111/jocd.16280
Zeinab Aryanian 1 2 3, Kamran Balighi 1 3, Azadeh Goodarzi 4 5, Zeinab Mohseni Afshar 6, Parvaneh Hatami 1
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31 References

1. Priya A, Adil M, Suhail Amin S, Mohtashim M, Bansal R, Alam M. Intralesional vitamin D3 in recalcitrant palmoplantar and periungual warts: a prospective, observational study. Acta Dermatovenerol Croat. 2019;27(4):215.
2. Kazeminejad A, Ghahari MJ, Hajheydari Z. Treatment of warts in children with focus on recalcitrant warts: a narrative review. J Pediatr Rev. 2020;8(4):237-246.
3. Liu PT, Stenger S, Li H, et al. Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science. 2006;311(5768):1770-1773.
4. Kavya M, Shashikumar BM, Harish MR, Shweta BP. Safety and efficacy of intralesional vitamin D3 in cutaneous warts: an open uncontrolled trial. J Cutan Aesthet Surg. 2017;10(2):90-94.
5. Bouillon R. Extra-skeletal effects of vitamin D. Front Horm Res. 2018;50:72-88.
6. Fathy G, Sharara MA, Khafagy AH. Intralesional vitamin D3 versus Candida antigen immunotherapy in the treatment of multiple recalcitrant plantar warts: a comparative case-control study. Dermatol Ther. 2019;32(5):e12997.
7. Raghukumar S, Ravikumar B, Vinay K, Suresh M, Aggarwal A, Yashovardhana D. Intralesional vitamin D3 injection in the treatment of recalcitrant warts: a novel proposition. J Cutan Med Surg. 2017;21(4):320-324.
8. Tamer F, Eren Yuksel M, Karabag Y. Pre-treatment vitamin B12, folate, ferritin, and vitamin D serum levels in patients with warts: a retrospective study. Croat Med J. 2020;61(1):28-32.
9. Shalaby ME, Hasan MS, Elshorbagy MS, Abo Raya AR, Elsaie ML. Diagnostic and therapeutic implications of vitamin D deficiency in patients with warts: a case-controlled study. J Cosmet Dermatol. 2022 Mar;21(3):1135-1142. doi:10.1111/jocd.14156
10. Tawfik N, Hussein HI, Hassan RM, Atwa MA. Assessment of serum 25-hydroxycholecalciferol level in patients with recalcitrant palmoplantar warts. Suez Canal Univ Med J. 2020;23(2):129-134.
11. Imagawa I, Suzuki H. Successful treatment of refractory warts with topical vitamin D3 derivative (maxacalcitol, 1α, 25-dihydroxy-22-oxacalcitriol) in 17 patients. J Dermatol. 2007;34(4):264-266.
12. Moscarelli L, Annunziata F, Mjeshtri A, et al. Successful treatment of refractory wart with a topical activated vitamin D in a renal transplant recipient. Case Rep Transplant. 2011;2011:368623.
13. Al-Sabak H, Al-Hattab M, Al-Rammahi M, Al-Dhalimi M. The efficacy of intralesional vitamin D3 injection in the treatment of cutaneous warts: a clinical therapeutic trial study. Skin Res Technol. 2023 Aug;29(8):e13442. doi:10.1111/srt.13442
14. Aktas H, Ergin C, Demir B, Ekiz O. Intralesional vitamin D injection may be an effective treatment option for warts. J Cutan Med Surg. 2016;20:118-122.
15. Naresh M. A study of effectiveness of intralesional vitamin D3 in treatment of multiple cutaneous warts. IOSR J Dent Med Sci. 2019;18(3):84-87.
16. El Sayed MH, Sayed FS, Afify AA. Intralesional zinc sulphate 2% versus intralesional vitamin D in plantar warts: a clinicodermoscopic study. Dermatol Ther. 2020;33(3):e13308.
17. Mohamed EEM, El Taieb MA, Abd El-Sabour GA. Intralesional vitamin D3 versus purified protein derivatives in the treatment of multiple cutaneous warts: comparative study. Egypt J Hosp Med. 2019;76(2):3589-3594.
18. Shaldoum DR, Hassan GFR, El Maadawy EH, El-Maghraby GM. Comparative clinical study of the efficacy of intralesional MMR vaccine vs intralesional vitamin D injection in treatment of warts. J Cosmet Dermatol. 2020;19:2033-2040.
19. Raveendra L, Raju BP, Dharam KK, Yadav VMK. Comparison of purified protein derivative and vitamin D in the treatment of recalcitrant warts. Clin Dermatol Rev. 2021;5(1):54.
20. Yousaf F, Raza N, Ahmed N, Sadiq S, Anwar A. Comparison of intralesional Vitamin D3 versus cryotherapy for management of plantar warts. PAFMJ. 2019;69(6):1304-1308.
21. Tawfik YM, Hosny AH, El-Gazzar AF, Bakr RM. Efficacy and safety of treating anogenital warts with intralesional vitamin D3 injection: a report on 20 Egyptian patients. Al-Azhar Assiut Med J. 2020;18(2):140.
22. Milante RR, Venida-Tablizo A, King-Ismael D. Efficacy and safety of single versus multiple intralesional immunotherapy with purified protein derivative (PPD) in the treatment of multiple verruca vulgaris. Int J Dermatol. 2019;58(12):1477-1482.
23. Ezquerra GM, Regaña MS, Millet PU. Combination of acitretin and oral calcitriol for treatment of plaque-type psoriasis. Acta Derm Venereol. 2007;87(5):449-450.
24. Singh M, Thakral D, Kar HK, Rishi N, Sharma PK, Mitra DK. Distinct clinico-immunological profile of patients infected with human papilloma virus genotypes 6 and 11. VirusDisease. 2017;28(2):200-204.
25. Abdel-Azim ES, Abdel-Aziz RT, Ragaie MH, Mohamed EA. Clinical and dermoscopic evaluation of intralesional vitamin D3 in treatment of cutaneous warts: a placebo-controlled study. J Egypt Women's Dermatol Soc. 2020;17(1):6.
26. El-Taweel AEA, Salem RM, Allam AH. Cigarette smoking reduces the efficacy of intralesional vitamin D in the treatment of warts. Dermatol Ther. 2019;32(2):e12816.
27. Attwa E, Elawady R, Salah E. ‘Cryo-immuno-therapy’ is superior to intralesional Candida antigen monotherapy in the treatment of multiple common warts. J Dermatol Treat. 2021;32(8):1018-1025.
28. Yeh MC-H, Tsai T-Y, Huang Y-C. Intralesional vitamin D3 injection in the treatment of warts: a systematic review and meta-analysis. J Am Acad Dermatol. 2020;82(4):1013-1015.
29. Kareem IMA, Ibrahim IM, Mohammed SF, Ahmed AAB. Effectiveness of intralesional vitamin D3 injection in the treatment of common warts: single-blinded placebo-controlled study. Dermatol Ther. 2019;32(3):e12882.

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Note: Both methods provide a much higher concentration of wart Vitamin D than from oral Vitamin D

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VitaminDwiki – Injection contains:

64 items in Vitamin D Injection category

• Vitamin D injections last longer (3 month vs 2 month) than loading doses
• Getting Vitamin D into your body shows the many ways of getting Vitamin D

• Injections are currently made by medical professionals into muscle
• Home injection of Vitamin D appears to be possible in the future
• Injections are useful for people who might forget to take their periodic supplement (children, elderly, etc) and those who cannot swallow or have poor digestion
• While Vitamin D2 is historically the common form, Vitamin D3 is far better
• Should check (if there is time) for possible allergic reaction to Vitamin D or lack of Magnesium for both for loading dose and injection
• Note 600,000 IU Vitamin D loading dose via capsules is 1/20th the cost($2.40) of an injection, and does not require a prescription
• 100,000 IU single dose of vitamin D - 2010 has the following
  
• Vitamin D injection lasts longer and has bigger response than weekly oral – Jan 2017 has the following
  
• Non-oral Vitamin D should be a better form for MS, food allergy, PTSD, etc. – many studies might include injection

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VitaminDWiki – Topical Vitamin D category contains:

Topical is one of the many ways of increasing the vitamin D in your body
Topical is 2X to 50X more expensive than oral form
Topical is great for those who not want to swallow pillls nor fortifiy their food/drink with Vitamin D
Topical is one of the many gut-friendly forms of vitamin D (good bioavailability for those with poor guts
Topical is especially good form to apply directly to skin problems:
    - i.e. Psoriasis  Warts  Burns  Acne  Eczema  Wounds  (lasts about a day)
    The skin, like most tissues of the body, can fully-activate Vitamin D locally - no liver nor kidney needed.
Provides perhaps 100X higher concentration of Vitamin D to that portion than if same dose were taken orally
There were 98 topical Vitamin D products on Amazon Sept 2024 Creams, oils, patches, nanoemulsions, etc.
   I prefer Nutrasal nanoemulsion form
Suspect that topical Vitamin D is best absorbed where the skin gets Vitamin D naturally
- - - face and hands vs the back or the inside of arms
Nanoemulsions can also be applied topically under the tongue and inhaled

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VitaminDWiki – Warts removed by vitamin D injection - many studies

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HPV and Vitamin D association - no consensus - Review Jan 2024

Relationship between human papillomavirus and serum vitamin D levels: a systematic review
BMC Infect Dis. 2024 Jan 13;24(1):80. doi: 10.1186/s12879-024-09006-8.
Seyedeh Maryam Khalili 1, Elnaz Haji Rafiei 1, Marjan Havaei 1, Leila Alizadeh 1, Fereshte Ghahremani 1, Zohreh Keshavarz 2, Ali Montazeri 3 4, Hedyeh Riazi 5

Background: Human papillomavirus (HPV) is one of the most prevalent sexually transmitted diseases worldwide. The present review was conducted to accumulate evidence on the relationship between cervicovaginal human papillomavirus infection and serum vitamin D status.

Methods: Electronic databases including Web of Science, Embase, Scopus, and PubMed were searched by different combinations of keywords related to "human papillomavirus" and "vitamin D", obtained from Mesh and Emtree with AND, and OR operators without any time restriction until December 24, 2022. Selection of articles was based on the inclusion and exclusion criteria. Newcastle-Ottawa Scale was used for quality assessment. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist was applied for reporting.

Results: In total, 276 citations were retrieved. After removing duplicates, and non-related articles, the full texts of 7 articles were reviewed including 11168 participants.

• Three studies reported that there was a positive relationship between vitamin D deficiency and cervicovaginal human papillomavirus while
• Three studies did not.
• One study showed a significant positive association between higher vitamin D stores and short-term high-risk human papillomavirus persistence.

Conclusions: The findings showed no firm evidence for any association between serum vitamin D level and cervicovaginal human papillomavirus infection, although the possible association could not be discarded. Further investigations are needed to reach sound evidence.
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44 References

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12. Albergamo A, Apprato G, Silvagno F. The role of vitamin D in supporting health in the COVID-19 Era. Int J Mol Sci. 2022;23(7):3621. https://doi.org/10.3390/ijms23073621 . - DOI - PubMed - PMC
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20. Shim J, Pérez A, Symanski E, Nyitray AG. Association between serum 25-hydroxyvitamin D level and human papillomavirus cervicovaginal infection in women in the United States. J Infect Dis. 2016;213(12):1886–92. https://doi.org/10.1093/infdis/jiw065 . - DOI - PubMed
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29. Troja C, Hoofnagle AN, Szpiro A, Stern JE, Lin J, Winer RL. Understanding the role of emerging Vitamin D biomarkers on short-term persistence of high-risk human papillomavirus infection among mid-adult women. J Infect Dis. 2021;224(1):123–32. https://doi.org/10.1093/infdis/jiaa711 . - DOI - PubMed
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300,000 IU monthly oral Vitamin D got levels to only 24 ng, no HPV benefit - 2021

The effect of vitamin D on the regression of human papilloma virus infection and metabolic parameters: a retrospective study
EUROPEAN J. OF GYNAECOLOGICAL ONCOLOGY, vol.42, no.2, pp.340-345, 2021 10.31083/j.ejgo.2021.02.2246
Koc S., KURT S., İLGEN O., Timur H. T., Uslu T.

Purpose: Human papillomavirus (HPV) is the primary cause of cervical cancer. Our study aims to evaluate the effects of vitamin D on HPV regression, related cytological pathologies and various metabolic parameters.

Materials and methods: 100 high-risk HPV positive patients, who were detected from hospital database, were divided into 2 groups as those who received vitamin D supplements (n = 50) and did not receive vitamin D supplements (n = 50). We determined the changes in serum vitamin D concentrations, metabolic parameters of patients and regression of HPV after 6 months. Then, we compared the results of patients who took vitamin D supplements, and those who did not.

Results: Patient characteristics of both groups were similar in terms of smoking, using oral contraceptives, operation status, body mass index, and mean age of first coitus. Considering the findings of our study, the difference in rate of HPV regression was not significant in the group with a history of vitamin D use (P = 0.804). Regarding metabolic parameters, we observed significant decrease in insulin (P < 0.001), triglyceride (P = 0.019), and CRP (P < 0.001) levels in the group with a history of vitamin D use.

Conclusion: According to our findings, vitamin D supplementation does not significantly increase the rate of HPV regression. On the other hand, its metabolic effects are noteworthy. It has positive effects on glucose homeostasis and lipid profile. In the light of previous studies, vitamin D may be helpful in the treatment of vaginal infections, nonetheless it is not a as effective concerning cervical HPV infections.
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HPV 1.8X more likely if low Vitamin D - Nov 2020

Understanding the role of emerging vitamin D biomarkers on short-term persistence of high-risk HPV infection among mid-adult women - Nov 2020
J Infect Dis,. 2020 Nov 17;jiaa711. doi: 10.1093/infdis/jiaa711
Catherine Troja 1, Andrew N Hoofnagle 2, Adam Szpiro 3, Joshua E Stern 4, John Lin 1, Rachel L Winer 1

Background: Associations between vitamin D biomarkers and persistent high-risk human papillomavirus (hrHPV) detection have not been evaluated.

Methods: 2011-2012 stored sera from 72 women ages 30-50 years with prevalent hrHPV (n=116 type-specific infections) were tested for 5 vitamin D biomarkers: 25(OH)D and 4 emerging biomarkers, 1,25(OH)2D, 24,25(OH)2D, free vitamin D, and vitamin D binding protein (DBP). hrHPV detection patterns (persistent versus transient/sporadic) were determined using cervicovaginal swabs collected monthly for 6 months. Associations between vitamin D and short-term type-specific hrHPV persistence were estimated using logistic regression. Our primary exposure was continuous 25(OH)D, with additional biomarkers evaluated as secondary exposures. Primary models adjusted for age, race, BMI, education, contraceptives, smoking, season, and calcium/phosphate levels. Sensitivity analyses restricted from 19 hrHPV types to 14 used in cervical cancer screening.

Results: In primary analyses, non-significant positive associations with hrHPV persistence were observed for measures of 25(OH)D and 24,25(OH)2D. Associations were stronger and significant restricting to 14 hrHPV types (25(OH)D per 10ng/mL increase:

• aOR=1.82,95%CI:1.15-2.88 and
• aOR=4.19,95%CI:1.18-14.88 DBP-adjusted;
• 25(OH)D≥30 vs <30ng/mL: aOR=8.85,95%CI:2.69-29.06;
• 24,25(OH)2D: aOR=1.85,95%CI:1.18-2.88).
• 1,25(OH)2D was unassociated with persistence.

Conclusions: Serum vitamin D measured by multiple biomarkers showed positive associations with short-term hrHPV persistence that were significant only when restricting to 14 clinically-relevant hrHPV types.

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HPV 3X more likely if low Vitamin D - 2016

Association Between Serum 25-Hydroxyvitamin D Level and Human Papillomavirus Cervicovaginal Infection in Women in the United States.
J Infect Dis. 2016 Jun 15;213(12):1886-92. doi: 10.1093/infdis/jiw065
Shim J1, Pérez A2, Symanski E3, Nyitray AG3.
1 Department of Business Intelligence and Analytics, Texas Children's Health Plan, Houston.
2 Department of Biostatistics, University of Texas School of Public Health, Austin.
3 Department of Epidemiology, Human Genetics, and Environmental Sciences, University of Texas School of Public Health, Houston.

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BACKGROUND:
A sufficient level of vitamin D enhances protection against several infectious diseases; however, its association with cervicovaginal human papillomavirus (HPV) infection has not been studied.

METHODS:
Data for this cross-sectional study were from National Health and Nutrition Examination Survey 2003-2006. A total of 2353 sexually active women for whom cervicovaginal HPV infection status and serum 25-hydroxyvitamin D (25[OH]D) level were known were studied. Associations between serum 25(OH)D levels (continuous and categorical forms) and cervicovaginal HPV infection (due to high-risk HPV or vaccine-type HPV) were estimated using weighted logistic regression.

RESULTS:
After adjustment for age, race/ethnicity, and marital status, the odds of high-risk HPV infection were increased per each 10 ng/mL decrease in serum 25(OH)D level (adjusted odds ratio [aOR], 1.14; 95% confidence interval [CI], 1.02-1.27). Similarly, the odds of vaccine-type HPV infection were increased in women with vitamin D levels that were severely deficient (serum 25[OH]D level, <12 ng/mL; aOR, 2.90; 95% CI, 1.32-6.38), deficient (12-19 ng/mL; aOR, 2.19; 95% CI, 1.08-4.45), and insufficient (20-29 ng/mL; aOR, 2.19; 95% CI, 1.22-3.93), compared with those with vitamin D levels that were sufficient (≥30 ng/mL).

CONCLUSIONS:
Cervicovaginal HPV prevalence is associated with less-than-optimal levels of serum vitamin D.

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See also web

• 40 HPV strains cause Cancer Mercola Dec 2022
  • cervical, penile, oral, vaginal, vulvar and anal cancer.
  • "Ninety percent of HPV infections resolve on their own without treatment, as a well-functioning immune system will keep the virus in check. In rare cases, however, infection with a high-risk HPV that remains untreated and unchecked may turn into cancer."
  • "In the U.S., 3% of all cancers in women and 2% of cancers in men are related to untreated chronic HPV infection.2"
• 7 Million American Men Carry Cancer-Causing HPV NYT Oct 2017
  "The study, in the Annals of Internal Medicine, found that 11 million men and 3.2 million women in the United States had oral HPV infections. Among them, 7 million men and 1.4 million women had strains that can cause cancers of the throat, tongue and other areas of the head and neck."
  “The difference in oral HPV infection between smokers and nonsmokers is staggering,”   Note by VitaminDWiki: Smoking reduces vitamin D - many studies
• Natural Herbal HPV "Cure" Discovered GreeMedInfo Jan 2018
  curcumin (which activates the vitamin D receptor), reetha, amla and aloe vera vaginal cream

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ChatGPT description of HPV Jan 2024

HPV stands for Human Papillomavirus, a group of more than 200 related viruses. Some types of HPV are considered high-risk because they can cause cancer, including cervical cancer in women, as well as other types of cancer in both men and women. Other types of HPV can cause warts on different parts of the body, including genital warts.

Most HPV infections don't lead to cancer and go away on their own within two years. However, the infection can persist and cause long-term problems. Vaccines are available that can protect against the most dangerous types of HPV and are typically recommended for preteens, though they can be given to older individuals as well.

HPV is the most common sexually transmitted infection, and most sexually active people will get some type of HPV at some time in their lives, often without realizing it. It's important to have regular health check-ups that include screening for HPV-related diseases, such as cervical cancer, especially for those who are sexually active.

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