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Cervical Dysplasia

MagazineJuly 2012 (Vol. 23 Issue 4)Cervical Dysplasia

This is a scary diagnosis, but it doesn't mean you have cancer-and there's plenty you can do to slash your risk of developing cancer in the future if you've ever had an abnormal Pap smear test result, you've probably heard of cervical dysplasia, the name doctors have given to abnormal changes in the cells on the inner surface of the cervix-the lowest portion of the womb

This is a scary diagnosis, but it doesn't mean you have cancer-and there's plenty you can do to slash your risk of developing cancer in the future if you've ever had an abnormal Pap smear test result, you've probably heard of cervical dysplasia, the name doctors have given to abnormal changes in the cells on the inner surface of the cervix-the lowest portion of the womb.

Such changes are not cancer-and usually have no symptoms-but they are con-sidered 'pre-cancerous', which means that doctors believe they could potentially lead to cancer if left untreated.
The chances of cervical dysplasia-also known as 'cervical intraepithelial neoplasia' (CIN)-progressing to invasive cancer depends on the severity (its extent in the epithelium) of cell abnormality. Research on the natural course of CIN suggests that mild dysplasia, or CIN 1, will progress to cancer just 1 per cent of the time, whereas moderate (CIN 2) or severe (CIN 3) dysplasia will become cancerous about 5 per cent and 12 per cent of the time, respectively.

In a significant proportion of cases, the abnormal cellular changes revert to normal on their own. In cases of CIN 1, this figure is about 60 per cent whereas, with CIN 2, it's 40 per cent and, with CIN 3, it's just over 30 per cent. The rest of the time, the dysplasia is more likely to simply stay as it is rather than progress to a more severe form, or to cancer (Int J Gynecol Pathol, 1993; 12: 186-92).

Despite these reassuring findings, doctors prefer to err on the side of caution and will usually recommend treatment for cases of moderate-to-severe dysplasia and for persistent mild dysplasia. Treatments vary, but all are invasive and come with both short-and long-term risks (see box, page 19). What's more, these treatments rarely take into consideration what's actually causing the abnormal cells. In fact, growing evidence suggests that a number of dietary and lifestyle factors may play a role in cervical dysplasia, and that it may be possible to reverse these abnormal cell changes through natural means.

Nutritional deficiencies
Almost all cases of cervical dysplasia are thought to be caused by the sexually transmitted human papillomavirus (HPV), some strains of which are associated with cervical cancer. However, not all women with the virus develop cervical dysplasia or cervical cancer, so other factors to do with the individual are likely to be involved.

One of these factors is nutritional deficiencies. Low levels of certain nutrients-particularly folate (vitamin B9)-have been linked to cervical dysplasia in several studies, possibly because such a state leaves the body not fully equipped to fight off a viral attack.

In one study of over 500 women with and without CIN, Polish researchers reported significantly lower levels of folate in those with CIN and HPV compared with those who had normal Pap smear results. They also found that having low levels of antioxidants, such as vitamins C, E and A, in combination with low folate levels increased the risk of CIN developing (Eur J Gynaecol Oncol, 1997; 18: 526-30).

In another study, involving 294 cases of dysplasia and 170 controls, US scientists at the University of Alabama found that women with red-blood-cell folate levels at or below 660 nmol/L were five times more likely to be infected with HPV 16-one of the more aggressive forms of the virus that is strongly associated with CIN 3 and cervical cancer (JAMA, 1992; 267: 528-33).

It certainly makes sense that a lack of sufficient folate (even when no symptoms are evident) may be involved in cervical dysplasia, as the vitamin is crucial for the synthesis and repair of DNA. The cells of the cervical lining replace themselves every 7-14 days, so they are constantly forming DNA, thereby giving the HPV genetic material many opportunities to incorporate itself into the host DNA. When folate levels are low, DNA susceptibilities are more frequent, increasing the risk of attack by carcinogens and viruses (Altern Med Rev, 2003; 8: 156-70).

However, it's not yet clear whether supplementing with folic acid, the man-made form of folate, can reverse cervical dysplasia.

In a six-month trial of 235 women with CIN 1 or 2, half were given 10 mg of folic acid daily while the other half received a placebo. At the end of six months, there were no significant differences between the two groups in terms of dysplasia, biopsy results or the prevalence of HPV-16 infection (Am J Obstet Gynecol, 1992; 166: 803-9).

In another double-blind trial, however, involving women with CIN 1 or 2 taking oral contraceptives, those taking folic acid supplements (again at 10 mg/day) for three months had significantly better biopsy scores by the end of the study, and their cellular abnormalities were also improved (Am J Clin Nutr, 1982; 35: 73-82). It may be that oral-contraceptive users respond well to folic-acid supplements, as the Pill is known to deplete levels of folate in the body.

Although more research is needed on folic acid's potential to help cervical dysplasia, taking the supplement appears to be safe (try a dose of up to 5 mg daily in combination with other B vitamins, especially B6 and B12), and may be worth considering as an aid to improving cell abnormalities and reducing the risk of cervical cancer.

Low levels of carotenoids-antioxidant pigments found in fruit and vegetables-have also been linked to CIN as well as cervical cancer. In one study, blood levels of the carotenoids beta-carotene, lycopene and canthaxanthin were significantly lower in women with CIN or cervical cancer compared with women without these conditions (Clin Cancer Res, 1996; 2: 181-5). Similarly, low levels of alpha-carotene, zea-xanthin and lutein have also been associated with an increased risk of CIN (Cancer Epidemiol Biomarkers Prev, 2001; 10: 1219-22). A trial of beta-carotene supplementation, however, reported that 30 mg/day was not effective for improving high-grade CIN (Cancer Epidemiol Biomarkers Prev, 2001; 10: 1029-35).

Vitamin A (retinol) is another nutrient that appears to be involved in CIN. Studies show that vitamin A intakes and levels of retinol in the blood are more than four times lower in women with cervical dysplasia whose condition progresses to its most severe form, or to invasive cancer, compared with those whose disease regresses (Cancer Invest, 1999; 17: 253-8).
What's more, studies of the use of topical vitamin A to treat CIN have had promising results. One of these, which used a collagen sponge insert and a cervical cap to directly deliver vitamin A to the cervix (in the form of all-trans-retinoic acid), a short course of treatment appeared to enhance the regression of CIN 2. In the placebo group, 27 per cent of the CIN-2 patients had returned to normal after six months vs 43 per cent in the retinoic-acid group. However, no effect was seen in the more severe CIN-3 patients (J Natl Cancer Inst, 1994; 86: 539-43).

Other factors
Besides not getting enough essential nutrients, other lifestyle factors may be related to cervical dysplasia. Smoking is associated with a higher risk of HPV infection as well as CIN and cervical cancer. In fact, the International Agency for Research on Cancer has listed cervical cancer among those causally related to smoking (ISRN Obstet Gynecol, 2011; 2011: 847684).
Even passive smoking may cause cervical abnormalities, according to a recent study (Am J Obstet Gynecol, 2011; 204: 213.e1-e6).

More controversial is the idea that oral contraceptives could be contributing to CIN and cervical cancer. While your doctor may tell you that there's no evidence to suggest a connection, a recent meta-analysis that pooled the results of 28 separate studies found that, compared with women who have never used oral contraceptives, Pill users have a significantly increased risk of cervical cancer, and the risk increases the longer they've been using it (Gynecol Endocrinol, 2011; 27: 597-604).

According to researchers at the Radboud University Nijmegen Medical Centre in The Netherlands, oral contraceptives increase the chances of HPV infection while reducing the likelihood that the body can effectively clear it from the system. This may result in persistence of the virus, CIN and, possibly, cervical cancer (Ned Tijdschr Geneeskd, 2008; 152: 1717-8). As already mentioned, oral contraceptives have also been linked to folate deficiency (Can Fam Physician, 1985; 31: 1523-6), which might explain the link between these drugs and cervical problems (see above).
A final factor to consider is psychological stress. A study by the Fox Chase Cancer Center in Cheltenham, PA, revealed a significant association between levels of perceived stress and the immune response to HPV in women with cervical dysplasia. Those who reported feeling more stressed were more likely to have an impaired HPV-specific immune response, meaning that the immune system can't fight off the virus effectively (Ann Behav Med, 2008; 35: 87-96). The results suggest that stress might be another piece of the puzzle that helps to explain why some women with HPV get CIN and cervical cancer, while others manage to avoid them.

An holistic approach
Ultimately, these findings sug-gest that a range of environ-mental factors-in particular, the foods and chemicals we put into our bodies-may have a role to play in the development of CIN and cervical cancer. An holistic approach that includes getting enough of the right nutrients, avoiding smokers/ smoking and synthetic hor-mones, and managing stress may therefore be useful for the prevention and treatment of these conditions.
If you've been diagnosed with CIN, talk to your doctor about the severity of the problem and whether urgent treatment is required. If it's not, then work with a qualified naturopathic practitioner to address the possible causes and get yourself tested again after a few months.
Joanna Evans

Factfile: Treatments for CIN

CONVENTIONAL TREATMENTS

  • Large loop excision of the transformation zone (LLETZ). With LLETZ, or LEEP (loop electrosurgical excision) as it's known in the US, a thin wire loop heated with an electric current is used to cut out the area of the cervix where abnormal cells have developed. It's the most common treatment for CIN in the UK and is said to have a 90- to 95-per-cent cure rate. Risks include bleeding, infection and problems during pregnancy such as having a preterm or low-birth-weight baby.
  • Cone biopsy. In this procedure, a cone-shaped wedge of abnormal tissue is surgically removed from the cervix. It reportedly has a 70- to 98-per-cent cure rate. The risks are similar to those with LLETZ (Lancet, 2006; 367: 489-98), but it's also been linked to perinatal death (BMJ, 2008; 337: a1284; doi: 10.1136/bmj.a1284). If general anaesthesia is required, there are also risks associated with that, too.
  • Cryotherapy. This involves using a cold probe to freeze away the abnormal cells. It's said to destroy 99 per cent of abnormal tissue. Risks include bleeding, infection and scarring, and it's also been linked to higher rates of subsequent cervical cancer compared with other treatments (J Natl Cancer Inst, 2009; 101: 721-8).
  • Laser therapy. This uses a laser to pinpoint and burn away the abnormal cells, and has a 90-per-cent cure rate. There may be less scarring than with cryotherapy, but it's associated with more pain and bleeding (Gynecol Oncol, 1985; 22: 23-31).

PROMISING NATURAL TREATMENTS
  • Green tea extracts. A Korean study of 51 women with various stages of cervical dysplasia and HPV infection investigated the effects of green tea extract in the form of a topically applied ointment or as a capsule taken by mouth. Overall, a 69-per-cent response rate was noted for treatment with green tea extracts compared with a 10-per-cent response rate in the untreated controls (Eur J Cancer Prev, 2003; 12: 383-90).
  • Indole-3-carbinole (I3C). Found naturally in cruciferous vegetables such as cabbage, broccoli and brussels sprouts, I3C is also a popular supplement. In a trial of 30 patients with CIN 2/3, one group received 200 mg/day of I3C and another group received 400 mg/day of I3C, while a third group received a placebo. After 12 weeks, a biopsy was done to see if there were any changes. None (0 of 10) of the patients in the placebo group had complete regression of CIN, whereas four of eight patients in the 200 mg/day arm and four of nine patients in the 400 mg/day arm had complete regression of their dysplasia (Gynecol Oncol, 2000; 78: 123-9).
  • Escharotic treatment, which involves the local application of natural preparations to the cervix to dissolve the uppermost layer of cells, is showing some promise for the treatment of cervical dysplasia (Altern Med Rev, 2003; 8: 156-70; Integr Cancer Ther, 2009; 8: 164-7).

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