Abstract
Objective:
Cervical cancer is a serious challenge, and pharmacologic nonsurgical treatment of precursor human papilloma virus (HPV) conditions does not exist. The Centers for Disease Control and Prevention (CDC) estimates 36,500 new cases of (HPV)-associated cancers per year. The purpose of this report is to illustrate a method that could eliminate HPV positivity to control precancerous lesions before they develop carcinoma. Eighty-six percent of cervical cancers contain HPV as a likely causal factor.
Design/Setting:
Two patients sought private practice integrative medicine: one for chronic HPV-induced cervical dysplasia, the other with lichen sclerosis post squamous cell carcinoma (SCC).
Methods:
The two patients were included because they asked for help with their conditions, since no previous medical help was either offered or successful. Patients were treated with a systematic integrative approach, designed to normalize leaky gut, and microbiome to reduce systemic antigenic stimulation. Also, berberine and curcumin were given, based on in vitro data on their effectiveness for treating HPV-induced oncogenic changes in cells. Those herbal derivatives were obtained from an organic chemist who maintained strict quality control.
Results:
A patient with oncogenic HPV-induced chronic severe cervical dysplasia had a dramatic improvement of dysplasia and HPV positivity. The patient with lichen sclerosis and atrophicus had a 75% improvement in the appearance of her condition, and her suspected SCC was in situ.
Discussion:
From this limited case report, it appears that a combination of integrative methods, plus curcumin and berberine, can clear oncogenic HPV and reverse dysplastic and oncogenic changes in the cervix as well as autoimmune changes in the vaginal area.
Conclusion:
The combination of integrative methods and curcumin and berberine helped patients with oncogenic HPV-induced cervical dysplasia and autoimmune and cancer-forming lichen sclerosis. Considering the high prevalence of HPV-induced cervical dysplasia, and the lack of treatment, this study should be repeated at a larger level.
Introduction
Herbs have long been used for treatment of illness, and a significant fraction of current medications are derived from herbs. 1 Berberine and curcumin are herbal components that have been shown historically, clinically, and in vitro to have anticancer and antiviral effects.
Human papilloma virus (HPV) infects the cervix, and is transmitted sexually. Several types of HPV have been identified that have been shown to be carcinogenic. Lichen sclerosis and atrophicus (LS&A), sometimes referred to as lichen sclerosis, is a chronic likely autoimmune condition of the vaginal area, with both thinning, thickening, and discoloration of the internal and external skin, which can be scarred, pruritic or painful, and sometimes evolves into squamous cell carcinoma (SCC). HPV, and other viral or bacterial infections, has been considered, but not proven, as a causal factor. 2
Patients with chronic debilitating conditions, such as HPV-induced precancerous dysplasia and LS&A, do not have good medical options for treatment in the realm of conventional Western Medicine. 3 Topical corticosteroids, estrogen, and testosterone often give temporary relief, but may also contribute to atrophy. The condition sometimes evolves into SCC, as it did in the patient being presented. This report is on the success of a combination of restoring organ function, and the use of two highly verified and purified herbal preparations in improving two patients with these disorders.
Their choice was based on data in the literature, their use in Western, Ayurvedic, and Chinese herbal medicine, the latest in vitro cellular studies, and information in the medical literature on the pathophysiological biochemical pathways in those disorders that they inhibit.
Autoimmune conditions are likely initiated and perpetuated by cellular immune reactions to cross-reactive antigens entering the body and recognized in conjunction with human leukocyte antigen (major histocompatibility complex) and tissue-specific antigens. If there is an unfortunate similarity between initiating antigens and epitopes on specific tissues, with or without chemical, viral or microbial modification, then those molecular mimics become targets for an immune attack. 4 In some cases, such as this one, chronic inflammation leads to development of cancer.
The largest sources of foreign antigens include the diet, microbiome, and environmental chemicals. Changing diet to reduce both inflammatory stimuli and the flora and lipopolysaccharides in the resulting microbiome, and to reduce leakage of those substances into the lymphatics and circulation, is one method to reduce autoimmune stimuli.5,6 Reducing inflammation overwhelm frees up normal T-Reg suppression of inappropriate immune responses. 7
Enhancing the degradation of such antigens by improving digestion and overwhelmed hepatic and other eliminative function also helps. Supporting adrenal function with endogenous corticosteroids aids in suppressing inappropriate immune reactivity. A combination of these methods can help restore normal physiological and immune function, and calm down autoimmune processes.
Methods: Case Reports and Results
Patient A had a history of a parasite treated after 5 years of being undetected, multiple food sensitivities, and of being treated by a practitioner for heat in the liver in addition to being followed by a gynecologist/oncologist. She was followed initially for mild acne, fatigue, food sensitivities, constipation, insomnia, premenstrual syndrome (PMS), and Candida overgrowth/sensitivity. She was given pancreatic enzyme for digestion; liver supportive herbs, caprylic acid, probiotics, and a reduced carbohydrate and yeast-related antigen free diet for Candida overgrowth; Perilla and quercetin for allergy and inflammation; marshmallow root for intestinal barrier protection; vitamin C, pantothenic acid, and multivitamins for adrenal support, all to heal her leaky gut to improve her fatigue and numerous conditions.
The regimen gave her mild symptoms reminiscent of her previous detox, 8 and more severe symptoms when she resumed the regimen again another month later. Aggravation of symptoms from effective treatment, known as Detox reactions, was not uncommon in the integrative medicine world among patients with chronic fatigue and Candida overgrowth. That included 10 days nausea, a day of vertigo, headaches, disrupted sleep, acne outbreaks on the back, aggravation of PMS symptoms, and dark dreams related to her past trauma. After that, her PMS symptoms and sleep improved, and she felt better than she had in a long time.
Although she had not been sexually active, she was found to have severe cervical dysplasia on examination and papanicolaou [PAP] (screen for cervical cancer) smear at around age 20 years, as a result of being raped as a small child. She was followed on a regular basis for persistent cervical dysplasia for >10 years with similar findings. Biopsy of the cervix showed acute and chronic cervicitis with immature squamous metaplasia, with immune stains positive for one marker of cervical intraepithelial neoplasia, K1-67, but negative for P-16, in metaplastic cells in November, 2017. Her PAP smear showed atypical squamous cells of undetermined origin, and was positive in the Aptima test for presence of oncogenic HPV. (Aptima detects DNA of any of 13 high-risk types
She was followed for this condition regularly, with continued similar findings, on physical examination and yearly repeated PAP smears. Biopsies at ages 22, 27, and 33 years, and annual examinations and PAP smears showed severe dysplasia but no carcinoma. After reviewing articles in the literature forwarded by Acharan Narula, PhD, she was placed on a 99% pure curcumin 450 mg2 three times/day (TID) 6 weeks after beginning her initial regimen, and berberine HCl 98% 200 mg2 TID 6 weeks after that, in addition to her other supplements.
Six weeks after starting curcumin, at her annual checkup, her cervix appeared to be completely normal, the Aptima test was negative for high-risk HPV, and was read as negative for intraepithelial lesion and malignancy. Owing to the clinical and microscopic improvement and clearing of evidence of high-risk HPV, there was no need for biopsy. She reduced her dosage from 1 TID to 1 two times/day (BID) for a year and then 1 berberine per day for another year, from other reputable companies.
Her cervix has remained clinically free of dysplasia and HPV, and she has gone on successfully to use homeopathic and other treatments to detoxify, and remain clear. All along she has done extensive therapy on her past emotional trauma and is currently well and leading a fulfilling life.
Patient B was diagnosed with lichen sclerosis in 2005. She used clobetasol on and off topically since. She had a partial radical vulvectomy on April 2008 for SCC. Her PAP smears were abnormal and culture showed C. difficile. She was told she had a virus not usually associated with cancer, but no report was provided other than a positive vaginal culture for C. difficile, and no abnormal HPV was identified. She was also found to have vitamin D deficiency (known to depress both immunity and autoimmunity), mild celiac disease, obesity, and a history of recurrent Candida overgrowth.
She had an emergency hysterectomy in 2010. On examination, she had extensive erythema, widespread erosions of different depths, and white areas of atrophy in the vulvar area. History, physical, and applied kinesiology-based muscle response testing suggested intestinal Candida overgrowth, leaky gut, weakness of digestion, liver function, pancreatic function, and weakened adrenal function, with an open ileocecal valve. Several supplements were given to remedy those conditions, including psyllium, probiotics, caprylic acid, quercetin, silymarin, pantothenic acid, adrenal herbs, a supplement for increasing ATP activity, and more, with a low yeast diet.
She reported slight improvement off gluten and sugar, and some further improvement initially, on supplements to remedy Candida and leaky gut, as in the mentioned patient.
She also added berberine 400 mg TID and curcumin 900 mg TID for occult viral infection (or possible unidentified HPV) causing the lichen sclerosis and suspected SCC that was removed for a second time. An additional supplement from Narula contained Coptis Chinensis, berberine, Sophora flavescens, 9 and baicalin, acting as an antiviral.
When she returned 6 weeks later, she no longer itched and was less uncomfortable in the vaginal area, had lost ∼15 Kilograms (Kg), had much less bloating, and her plantar fasciitis had cleared to the extent that instead of being able to just walk around her apartment before developing pain, she could walk 3 Kilometers (Km) on her treadmill at a time. Her vulvar area looked somewhat improved in 3 weeks, according to her gynecologist/oncologist, and 75% improved several weeks later! An intravaginal excision for SCC a month later revealed only SCC in situ. She continued intermittent use of curcumin, berberine, probiotics, some supplements, and two other Narula antiviral herbal preparations over the next 2 years, with intermittent continued improvement
Discussion
The implication of this limited case report is that reduction of gut microbiome and food antigens into the lymphatics along with antiviral, anti-inflammatory, and anticancer herb-derived products including curcumin and berberine can improve precancers and precancerous autoimmune conditions including oncogenic HPV-induced cervical dysplasia and lichen sclerosis.
This study should be repeated at a much wider level to show whether this is a viable method for preventing HPV-induced cancer and autoimmune disease.
Both aspects of the integrative treatments likely contributed to the improvement by addressing confounding variables such as disturbed microbiome and leakage of lipopolysaccharides (the cell membranes of gram negative bacteria) into the lamia Propria, lymphatics, and circulation through a leaky gut, causing modification of endothelial cell presenter epitopes, leading to increased targets for cross-reactive immune responses. 10
There is no Western medical noninvasive treatment for cervical dysplasia and eliminating carcinogenic HPV virus, so “watchful waiting” with periodic PAP smears and biopsy is the norm until finding cervical carcinoma dictates more aggressive surgical procedures. There is a great need for early treatment that reduces this progression. In addition, certain HPV types such as HPV 18 have been associated with a poor prognosis if cervical carcinoma develops. HPV has been associated with other cancers of the urogenital tract including the bladder.11–13
Berberine is a molecule known to have anticancer, antiviral, 14 and antidiabetic effects. An admittedly low-quality data-based meta-analysis in the Chinese literature suggests that untranslated Chinese “herbal detoxification preparations” can improve HPV clearance and reduce cervical intraepithelial neoplasia. 15 Berberine has been shown to induce apoptosis in cervical cancer cells in vitro. It does so by activating AP-1, downregulating cFos oncogene activity, and suppressing human telomerase reverse transcriptase inhibiting growth of the cervical cancer cell line. Higher doses induced apoptosis.16,17
Curcumin has also been shown to control cervical cancer cells by inhibiting expression of oncogenes E6 and E7, activation of nuclear factor kappa B-induced tumor necrosis factor alpha downregulation, downregulation of COX-2 expression and binding, and binding of AP-1. A number of mechanisms result in apoptosis of cervical cancer cells.18,19 In light of lack of therapeutic options offered to the patient, the chronic history, chance of developing frank cervical carcinoma, and the in vitro and historic evidence that these herbs could control carcinogenic HPV virus, they were offered to the patient, and had a dramatic effect in controlling her chronic dysplasia.
Host defense mechanisms were also likely enhanced by these herbs. It appears that a combination of the restoration of normal organ function, which reduces autoimmune aspects of the patients' conditions, as well as specific anticancer and antiviral effects of berberine and curcumin, was likely to be responsible for both patients' improvement. Risk from herbs such as curcumin from turmeric, and lacking double-blind human studies can be justified by its large margin of safety, its widespread use in India, and its documented and traditional use for inflammation, infection, and cancer: three of the issues in the patients presented.
These studies should be expanded due to the potential cancer prevention benefit of this method as a treatment for oncogenic HPV.
Conclusion
These cases suggest that antiviral anticancer herbal components, such as berberine plus curcumin, combined with restoring more normal digestive, eliminative, and physiological function, can improve LS&A and HPV-induced dysplasia. Further such studies are warranted, understanding that an integrative approach needs to address individual specific variables regarding exposure, microbiome, diet, and genomic factors, specific to the individual and not just the disease.
It is possible that either berberine or curcumin together or alone could be helpful in controlling LS&A and or cervical dysplasia, however, other benefits seemed to accrue, and treatment was done to help the patients rather than as a study. Control of Candida and its mycotoxins may have also benefited the conditions, besides healing leaky gut and removing cross-reactive antigens.
Other healing systems may take account of an aggregate of diet and emotional factors yielding different choices for different individuals with the same named condition. It is important to bring into Western medicine understandable combinations of useable therapeutics, where none currently exist, to help those who are suffering, rather than waiting for untoward developments that require heroic and invasive treatment. Adding these herbal therapies and integrative treatments can enhance the success of current medical treatment for the majority, improve patient satisfaction, and help the minority of patients able and motivated to follow such protocols.
Combining broad data evaluation and individual care by practitioners might generate protocols that can be further evaluated. Appropriate use of high-quality herbal chemicals such as berberine and curcumin may be of great help in occult infection-induced vaginal autoimmune and precancerous conditions.
Footnotes
Acknowledgment
Discussions with Acharan S. Narula, PhD, Narula Research, LLC, Chapel Hill, North Carolina. USA have played a pivotal role in developing the successful protocol for HPV, presented in this case report.
Author Contribution
A.M.D. was entirely responsible for all aspects of writing of this article.
Consent and Release
Identifying information is not provided for the patients in the cases described. Both patients gave their permission for treatment and to tell their stories in this case report.
Author Disclosure Statement
Some aspects of the methodology of the integrative medicine-based reduction of inflammation are covered by patents applied for by the author. Those patents are not owned by any company, nor have they been monetized in any way. The author has no other conflicts of interest in writing this article, and no longer has a practice in which patients are seen and might benefit from referrals due to this article.
Funding Information
No funding was received for this article.