EFFECTS OF FOLATE ON CIN

The Effects of Folate on

Cervical Intraepithelial Neoplasia in Women with HPV
Lisa Marquand
May 13, 2015
CFS 453
Wanda Siu-Chan

EFFECTS OF FOLATE ON CIN

2
Abstract

Multiple studies have been conducted to determine if folate levels reduce the risk of
developing cervical intraepithelial neoplasia (CIN). Folate is known to regulate homocysteine
levels. Without proper folate levels, homocysteine levels may increase, causing potentially
hazardous health problems. The purpose of this paper is to determine the effects of folate on
cervical intraepithelial neoplasia in women with HPV.

Introduction and Background

Human papillomavirus (HPV) is a sexually transmitted infection. There are currently
more than 100 strains of HPV. Of the many strains, there are two strains known to cause cervical
cancer: HPV-16 and HPV-18 (Clifford et al, 2003). Early stages of HPV-16 and HPV-18
infection are known to cause abnormal or precancerous cells on the cervix, known as cervical
intraepithelial neoplasia (CIN).
HPV-related CIN can be detected through routine pap smears. If abnormal cells are
detected from the Pap smear results, a colposcopy is performed. During a colposcopy, the
physician uses a colposcope to view the epithelial tissue of the cervix. A vinegar solution is
applied in the cervical area; any color changes of the cervical tissue after the solution is applied
indicates areas of abnormal cells caused by the HPV infection. A biopsy is then taken of the
infected area and sent to the lab for testing.
The lab results determine the follow-up treatment of HPV-16 and HPV-18 infections. In
many cases, the immune system is able to fight the virus without further treatment (Gallenberg,
2013). This is usually seen with patients who have low risk epithelial squamous cells. High-risk
cases require further treatment, such as a loop electrosurgical excision procedure (LEEP) to

EFFECTS OF FOLATE ON CIN

remove precancerous cells. After a LEEP is performed, the patient is asked to return every 4-6
months for a repeat pap until there are no signs of abnormal cells and HPV test results are
negative.
The Center for Disease Control reported that about 79 million people are infected with
HPV, with about 14 million new cases each year; about 90% of people infected with HPV are
asymptomatic (CDC, 2015). The CDC also reported that more than 11,000 women get cervical
cancer each year (CDC, 2015). HPV types 16 and 18 mentioned earlier, account for about 70%
of cervical cancer cases worldwide (Clifford et al, 2003).
There are several techniques used today in the prevention and treatment of CIN and
cervical cancer. These treatments include sentinel lymph node biopsy, HPV vaccines, and target
therapy with the use of targeted drugs, hyperthermia, as well as drug treatment for pre-cancers.
In the sentinel lymph node biopsy, a radioactive blue dye is injected into the cancer, which is
then allowed to drain into possible infected lymph nodes; only those stained blue are removed
(ACS, 2015). HPV vaccines are used to help build immunity to HPV-16 and HPV-18. There are
also experimental vaccines being studied that help the immune system kill the cancer in patients
who currently have cervical cancer (ACS, 2015).
The use of drugs in the prevention and treatment of CIN and cervical cancer are currently
being studied to determine their effectiveness. Pazopanib is a tyrosine kinase inhibitor that is
used in the treatment of cervical cancer (Monk, et al, 2010). Diindolylmethane (DIM), which is
derived from plant sources such as cruciferous vegetables like cauliflower, broccoli, cabbage,
and brussel sprouts, was administered to patients with CIN. Results after 12 weeks showed
improvements (ACS, 2015) but sufficient evidence is needed to prove its effectiveness.

EFFECTS OF FOLATE ON CIN

Today there are many people who choose holistic practices as part of treatment or
prevention of diseases and infections, instead of relying on pharmaceutical drugs. During the
research for a topic regarding HPV in women and the treatment and prevention through diet, the
topic on the effects of folate levels in blood stream on CIN was discovered. After reviewing
several studies of the effects of folate levels on CIN in women with HPV, it was found that
increased levels of plasma folate could potentially reduce the risk of developing CIN in women
with HPV.

Research
Folate, vitamin B6, is an important micronutrient that aids in the regulation of
homocysteine levels. When acquired through diet, folate assists with homocysteine removal.
When there is a folate deficiency, increases in homocysteine levels can be observed (Bogolub,
2012). As a result of the folate deficiency and increase of homocysteine levels, there is an
increase in frequency of fragile DNA sites. This could impair DNA biosynthesis which is crucial
to cell growth, cell reproduction, and cell differentiation (Marshall, 2003).
A study at the University of Alabama was conducted to determine the influence of plasma
folate and vitamin B12 concentrations on cervical cancer risk. This study consisted of 376
premenopausal women who tested positive for HPV and were diagnosed with CIN (Piyathilake
et al, 2009). The results showed that women with supraphysiologic concentrations of plasma
folate (>19.8 ng/mL) who also had sufficient plasma vitamin B12 (200.6 pg/mL) had 70%
lower odds of being diagnosed with CIN 2+ (P = 0.04) when compared with women with plasma
folate of 19.8 ng/mL and plasma vitamin B12 of <200.6 pg/mL. (Piyathilake et al, 2009). This
shows the importance of B12 and a high concentration of folate to reduce the risk of CIN.

EFFECTS OF FOLATE ON CIN

In a follow-up study published in the Journal of Cancer Research, 345 women who were
at risk for developing CIN were tested. Hybrid capture 2 (HC-2) assay was used to evaluate the
women at 6-month intervals for 2 years (Piyathilake, 2004). The results reported show women
with higher folate levels were less likely to be repeatedly HC-2 test-positive (OR: 0.33; 95% CI,
0.130.86; P = 0.02) and more likely to become test-negative during the study (OR: 2.50; 95%
CI, 1.185.30; P = 0.02) (Piyathilake, 2004).

Discussion
HPV is one of the most common sexually transmitted infections in sexually active
individuals. The most important factor in prevention of HPV transmission or contraction is
practicing safe sex by the use of condoms. Staying informed and spreading awareness is
important to protect the health of the sexually active population. In addition to prevention and
protection, sexually active individuals should have routine examinations to be aware of his/her
current health status. Receiving proper treatment of HPV symptoms is just as important.
If an increase in folate concentration of blood serum can be proven to reduce the risk of
CIN in HPV-positive individuals, then a diet rich in foods that are high in folate should be
consumed in larger amounts to ensure higher folate levels are being met. Many fruits and
vegetables such as oranges, dark leafy greens, broccoli, brussel sprouts are good sources of
folate. Dried beans, peas, lentils, and breakfast cereals fortified with folate are all great sources
of folate. Nutrition in the Life Cycle lists pineapple juice and papaya juice as good dietary
sources of folate as well (Brown, et al., 2014). A folic acid supplement can be taken to ensure the
body has adequate folate levels. It is recommended that the supplement is taken on an empty

EFFECTS OF FOLATE ON CIN

stomach as it provides almost 100% bioavailability, compared to about 85% bioavailability when
consumed with food (Brown et al, 2014).
The daily recommended intake (DRI) of folate is as follows: 1 mcg from food source, 0.6
mcg folic acid consumed in fortified foods or a supplement take with food, 0r 0.5 mcg of a folic
acid dietary supplement (Brown, et al., 2014).
The results reported from the studies conducted show there may be an association
between an increase of plasma folate level and the reduced risk of developing CIN in women
who test positive for either of HPV-16 or HPV-18. Studies also show there is evidence that
vitamin B12 plays an important role in reducing the risk in women who test positive for HPV of
developing CIN. There is currently not enough evidence to prove high levels of folate reduce the
risk of CIN in women with HPV. Further studies would need to be conducted to prove this
claim.

References

EFFECTS OF FOLATE ON CIN

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