Pap smear, HPV, and natural approach to prevent cervical cancer

I received an email from a friend who became worried after getting an “abnormal” Pap smear screening result. It can be a fearful moment reading report show medical terms such as “low grade squamous intraepithelial lesion”. What does it mean? What is the risk of having cervical cancer? These are questions one will naturally ask. There are a lot of credible resources on the internet on Pap smear and cervical. Here are a number of them:

1. Making Sense of Your Pap & HPV Test Results (Centers for Disease Control and Prevention) (http://www.cdc.gov/std/hpv/pap/default.htm#sec3)
2. Pap Smear (Medicine.com) (http://www.medicinenet.com/pap_smear/article.htm)
3. Cervical Cancer (Singapore Cancer Society) (http://www.singaporecancersociety.org.sg/learn-about-cancer/types-of-cancer/cervical-cancer.html)

For ladies going for pap smear screening, do some reading beforehand. It can help you to make sense of what the test is about and how to interpret the results.

Pap smear and Cervical cancer

In a nutshell, Pap smear is a screening test for cervical cancer, i.e. cancer that grows on the cervix of the uterus. Infection by Human papillomavirus (HPV) is the most common cause of cervical cancer, with the virus found in 99.7% of women with cervical cancer [1]. HPV is a group of more than 200 subtypes of viruses that can infect animals and humans. HPV typically invades the skin surface and is the cause of many conditions, including common warts, flat warts, planter warts, and genital warts. Besides cervical cancer, HPV can also cause anal cancer and oral cancer. The transmission occurs primarily through skin-to-skin contact. Most of the infections by HPV typically heal by itself over time, with some lasting over 2-3 years. Infection by certain high risk HPV subtypes in the cervix over a period of time can lead to cell change that develop into cancer [2].
Pap smear is a procedure where a tidy bit of cells taken from the cervix is examined under the microscope to detect any abnormal cell change. Abnormal cell change detected will then be followed by an HPV test to confirm the presence of HPV and its subtype. Even if the Pap smear result is showing abnormal cell changes and an HPV test confirming the presence of HPV do not mean that one is having cervical cancer. In fact, only a very small percentage of Pap smear results turn out to be cancerous (0.1% of all Pap test results in United States [3] ; 0.37 per 1,000 screens in Singapore [4]). Most of the abnormal cell changes turn out to be minor lesions which may go away on their own [5]. Nonetheless, regular screening is very important as Pap smear is able to detect cell change that is caused by high-risk HPV types that may later develop into cancerous cells [2].

Natural approach to prevent cervical cancer

The body’s immune system is capable of eliminating the invading HPV by itself. This is the reason for minor lesions to regress over time. A weakened immune system can lead to frequent infection by HPV, evasion of the virus from immune system response, and eventual progression of the disease. Therefore, people with suppressed immune response are more susceptible to severe infection by HPV and cervical cancer. Suppressed immune system can be caused directly by illnesses (e.g. AIDS/HIV, kidney failure, sexual transmitted disease) or medication (e.g. immunosuppression therapy for autoimmune diseases), or indirectly by behavioural factors, such as smoking, chronic stress, unsafe sex, and unhealthy diet [6]. Therefore, the best approach to prevent cervical cancer is to maintain a strong body through living a healthy lifestyle.

Diet

In terms of diet, research has shown that the increase consumption of whole fruits and vegetables has a protective effect against the infection of HPV. Low intakes of fruits and vegetables are associated with a three-fold increase in the risk of HPV infection leading to cell change [7]. Therefore, for those who are infected with high risk HPV subtypes, it is imperative to increase intakes of fruits and vegetables. Among the recommended vegetables include dark-green, dark-yellow, and dark-orange coloured vegetables, as well as cruciferous vegetables such as cauliflower, cabbage, and broccoli. In addition, consumption of foods that provide rich sources of retinol and vitamin A, bioavailable calcium, antioxidants (including vitamin C, E, carotene, lutein and lycopene), as well as long-chain polyunsaturated fatty acids has also been shown to reduce the risk of cervical cancer.  These foods have antiviral and/or anti-oxidant properties that are believed to contribute to the observed risk reduction in population studies [7].

[table caption=”Important nutrients for cervical cancer prevention and their plant-based sources” colalign=”left|left”]
Nutrients, Plant-based sources
Vitamin A / Beta-carotene, “Spices (paprika, cayenne, chilli powder), sweet potato, carrot, kale, dried apricot, butternut squash, dried mint, Romaine lettuce, parsley”
Calcium, “Dark leafy greens (kale, watercress, kai lan, spinach), Chinese cabbage (pak choi), green cabbage, red cabbage, tofu, soy milk, okra (lady’s finger), broccoli, green beans, almonds”
Vitamin C, “Capsicum (yellow, red, green), guava, dark leafy greens, kiwi fruit, broccoli, berries (strawberries, raspberries, blueberries), citrus fruits (orange, pummelo, grapefruit, lemon), tomato, green pea, papaya”
Vitamin E, “Dark leafy greens, nuts (almonds, pistachios, pecans, walnuts), sunflower seeds, avocado, broccoli, squash, pumpkin, kiwi fruit”
Lutein, “Corn, dark leafy greens, grape, zucchini, kiwi, pumpkin, spinach, orange capsicum”
Lycopene,”Apricot, guava, papaya, grapefruit, carrot, tomato”
Long-chain polyunsaturated fatty acids, “Chia seed oil, flaxseed oil, walnut oil, soybean oil, hemp seed oil”
[/table]

Nutritional Supplements

Nutritional supplements should also be considered for anyone who has HPV infection, especially by the high risk subtypes.  Among the nutritional supplements that can be useful are:

1. High antioxidant drinks/extracts – these are typically made from extracts of different types of berries which are high in many different types of antioxidants (vitamin A, C, E, beta-carotene, etc.) There are many different products on the market. One example is NingXia Red from Young Living Essential Oils. This is a blend of many types of fruit juice (Goji berry, blueberry, plum, cherry, Aronia, and Pomegranate) and essential oils (grape, orange, Yuzu, lemon, and tangerine). Natural antioxidants play an important role in blocking the viral transformation process of HPV within infected cells and inhibit the growth of tumours [8].

2. 

   Curcumin – curcumin is the natural compound within turmeric that gives it the yellow colour. Turmeric is the rhizome of the plant Curcuma longa. It has been widely used as a traditional medicine, especially in Ayurveda, for thousands of years. The pharmacological properties of curcumin include anti-inflammatory, anti-oxidant, and anti-cancer [9]. It has been shown in a randomized controlled trial that topical application of curcumin is able to improve clearance of HPV infected lesions [10]. Research is now evaluating curcumin as a potential treatment for cervical cancer [9].  

3. Green Tea Extract – the epigallocatechin gallate (EGCG) compound within green tea is a strong antioxidant that has been shown to inhibit the growth of cervical cancer in laboratory testings using cell culture and animal models [11]. In a clinical trial involving 51 patients with HPV infected lesions, green tea extract was given to patients in the form of either capsules or ointments. The results show a 69% response rate in the treated group compared with a 10% response ratein the untreated control. Hence, green tea extract can be effective in treating HPV infected lesions [12].

   

4. Probiotics – The microenvironment within the virginal plays an important role in the protection against HPV infection. In a healthy vaginal, there are many good bacteria (Lactobacillus) that help to defend against pathogens and infections. Low numbers of Lactobacillus spp within the virginal can lead to the increase in diversity of bacteria within the microenvironment and the progression of HPV infection [13]. Supplementing with probiotics have been shown to shown to enhance clearance of HPV-related cervical lesions [14].
5. Folate and vitamin B12 – In a study involving 315 women diagnosed with high risk HPV 16 infection, it was found that women with higher levels of serum folate and vitamin B12 were at reduced risk of infection progression. It was suggested that folate and vitamin B12 can prevent further infection of HPV through a specific methylation action [15]. Therefore, ensuring sufficient level of folate and vitamin B12 level in the body through supplementation should be considered.

Conclusion

Regular screening with pap smear is important to uncover any early sign of HPV infection that may potentially develop into cervical cancer. Getting an “abnormal” Pap smear result can be a warning sign that the body’s immune system is weakened. Hence, to prevent cervical cancer, it is important to maintain a strong body through living a healthy lifestyle. Specific behaviour advices include stop smoking, reduce stress, and practise safe sex. Increase consumption of fruits and vegetables can help to protect against HPV infections. Regular consumption of dark-green, dark-yellow, and dark-orange coloured vegetables, and cruciferous vegetables such as cauliflower, cabbage, and broccoli is highly recommended. Supplementation with high antioxidant drink, curcumin, green tea extract, probiotics, folate and vitamin B12 should be considered to enhance the clearance of any HPV infected cervical lesions.

 

References

[1]         N.M. Nour, Cervical cancer: a preventable death., Rev. Obstet. Gynecol. 2 (2009) 240–4. doi:10.1111/j.1525-1497.2005.40158.x.

[2]         E.M. Burd, Human papillomavirus and cervical cancer., Clin. Microbiol. Rev. 16 (2003) 1–17. doi:10.1128/CMR.16.1.1-17.2003.

[3]         M. Safaeian, D. Solomon, Cervical Cancer Prevention – Cervical Screening: Science in Evolution, Obs. Gynaecol Clin North Am. 34 (2007) 739–ix. doi:10.1016/j.ogc.2007.09.004.Cervical.

[4]         A.Z. Jin, E.C. Louange, K.Y. Chow, C.W.L. Fock, Evaluation of the National Cervical Cancer Screening Programme in Singapore, Singapore Med. J. 54 (2013) 96–101.

[5]         National Cancer Institute, Understanding Cervical Changes: A Health Guide for Women, (2014). http://www.cancer.gov/types/cervical/understanding-cervical-changes/understanding-cervical-changes.pdf (accessed May 19, 2016).

[6]         P.-A. Dugue, M. Rebolj, P. Garred, E. Lynge, Immunosuppression and risk of cervical cancer, Expert Rev. Anticancer Ther. 13 (2013) 29–42. http://www.embase.com/search/results?subaction=viewrecord&from=export&id=L366336035.

[7]         H.J. Chih, A.H. Lee, L. Colville, C.W. Binns, D. Xu, A review of dietary prevention of human papillomavirus-related infection of the cervix and cervical intraepithelial neoplasia., Nutr. Cancer. 65 (2013) 317–28. doi:10.1080/01635581.2013.757630.

[8]         F. Di Domenico, C. Foppoli, R. Coccia, M. Perluigi, Antioxidants in cervical cancer: Chemopreventive and chemotherapeutic effects of polyphenols, Biochim. Biophys. Acta – Mol. Basis Dis. 1822 (2012) 737–747. doi:10.1016/j.bbadis.2011.10.005.

[9]         M.S. Zaman, N. Chauhan, M.M. Yallapu, R.K. Gara, D.M. Maher, S. Kumari, M. Sikander, S. Khan, N. Zafar, M. Jaggi, S.C. Chauhan, Curcumin Nanoformulation for Cervical Cancer Treatment., Sci. Rep. 6 (2016) 20051. doi:10.1038/srep20051.

[10]      P. Basu, S. Dutta, R. Begum, S. Mittal, P. Das Dutta, A.C. Bharti, C.K. Panda, J. Biswas, B. Dey, G.P. Talwar, B.C. Das, Clearance of cervical human papillomavirus infection by topical application of curcumin and curcumin containing polyherbal cream: A phase II randomized controlled study, Asian Pacific J. Cancer Prev. 14 (2013) 5753–5759. doi:10.7314/APJCP.2013.14.10.5753.

[11]      C. Zou, H. Liu, J.M. Feugang, Z. Hao, H.-H.S. Chow, F. Garcia, Green tea compound in chemoprevention of cervical cancer., Int. J. Gynecol. Cancer. 20 (2010) 617–24. doi:10.1111/IGC.0b013e3181c7ca5c.

[12]      W.-S. Ahn, J. Yoo, S.-W. Huh, C.-K. Kim, J.-M. Lee, S.-E. Namkoong, S.-M. Bae, I.P. Lee, Protective effects of green tea extracts (polyphenon E and EGCG) on human cervical lesions., Eur. J. Cancer Prev. 12 (2003) 383–90. doi:10.1097/01.cej.0000090186.08740.82.

[13]      A. Mitra, D.A. MacIntyre, Y.S. Lee, A. Smith, J.R. Marchesi, B. Lehne, R. Bhatia, D. Lyons, E. Paraskevaidis, J. V Li, E. Holmes, J.K. Nicholson, P.R. Bennett, M. Kyrgiou, Cervical intraepithelial neoplasia disease progression is associated with increased vaginal microbiome diversity., Sci. Rep. 5 (2015) 16865. doi:10.1038/srep16865.

[14]      V. Verhoeven, N. Renard, A. Makar, P. Van Royen, J.-P. Bogers, F. Lardon, M. Peeters, M. Baay, Probiotics enhance the clearance of human papillomavirus-related cervical lesions: a prospective controlled pilot study., Eur. J. Cancer Prev. 22 (2013) 46–51. doi:10.1097/CEJ.0b013e328355ed23.

[15]      C.J. Piyathilake, M. Macaluso, M.M. Chambers, S. Badiga, N.R. Siddiqui, W.C. Bell, J.C. Edberg, E.E. Partridge, R.D. Alvarez, G.L. Johanning, Folate and vitamin B12 may play a critical role in lowering the HPV 16 methylation-associated risk of developing higher grades of CIN., Cancer Prev. Res. (Phila). 7 (2014) 1128–37. doi:10.1158/1940-6207.CAPR-14-0143.