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Women's Health Update: Ovarian Cancer Screening Guidelines.

The US Preventive Services Task Force (USPSTF) recently published a recommendations statement based on updated evidence and a systematic review of screening for ovarian cancer. Ovarian cancer is the fifth most common cause of cancer-related death in women in the US. Only one in five ovarian malignant tumors are diagnosed when they are stage I disease, and if stage I, the survival rate is 90%. The problem is that most cases of ovarian cancer are diagnosed when they are in advanced stages and thus with a poor prognosis. The last USPSTF guidelines on this topic were published in 2012. The current guidelines are now updated based on a review of recent evidence regarding the benefits and risks of ovarian cancer screening in women who are considered average risk.

The key recommendations are as follows:

* Ovarian cancer screening is not recommended in average risk women.

* Screening (such as transvaginal ultrasound and/or a tumor marker, CA-125 blood test) does not reduce the mortality due to ovarian cancer.

* Transvaginal ultrasound and/or CA-125 tumor marker tests have low positive predictive value in average risk women.

* Unnecessary harms include surgery for women who do not have ovarian cancer.

* Harm due to ovarian cancer screening outweighs any benefits.

Commentary: I have been long familiar with the temptation of using transvaginal ultrasound and/or CA-125 testing as an ovarian cancer screening strategy. But I have also been familiar with their misleading results. Transvaginal ultrasound is definitely appropriate in assessing and even monitoring adnexal masses. In addition, serial CA-125 levels are used in following surgical treatment for ovarian cancer. But, for women who are asymptomatic and considered to be at average risk for ovarian cancer (e.g. no known mutation for hereditary cancer syndromes), the evidence results in an unchanged message: Screening in average risk women with transvaginal ultrasound and/or CA-125 testing should not be utilized. The American College of Obstetricians and Gynecologists and the American Cancer Society are all on the same page about these recommendations.

At the risk of countering guidelines, there are occasions where I feel compelled to test an asymptomatic woman. These have included a first-degree relative with ovarian cancer (no genetic testing in that relative or our individual woman), obesity, and a diagnosis of polycystic ovarian cancer syndrome (PCOS). A subset of women with PCOS may have an increased risk of ovarian cancer. If I have a patient with all three of these (mother with ovarian cancer + obesity + history of PCOS), I would likely recommend annual transvaginal ultrasound and CA-125 testing.

US Preventive Services Task Force. Screening for ovarian cancer: USPSTF Statement. JAMA. 2018 Feb 13; 319:588.

Henderson J, et al. Screening for ovarian cancer: Updated Evidence Report and Systematic Review for the USPSTF. JAMA. 2018;Feb 13; 319:595.

Cervical Cancer Screening Guidelines for Women Older Than 65

There have been many changes in cervical cancer screening guidelines, especially since 1988 and the publication of the Bethesda System in which the terminology and the three levels of CIN (cervical intraepithelial lesions) was replaced by LSIL (low grade squamous intraepithelial lesions) and HSIL (high grade intraepithelial lesions). In the last 40 years, with widespread use of cervical cancer screening, the incidence of and mortality from invasive cervical cancer has been significantly reduced. In 2002, the addition of human papilloma virus (HPV) testing to cytology testing led to longer screening intervals. In 2012, consensus guidelines were compiled by an expert panel from the American Society for Colposcopy and Cervical Pathology and supported by the American College of Obstetricians and Gynecologists (ACOG), the American Cancer Society (ACS) and the US Preventive Services Task Force (USPSTF). Amongst the extensive guidelines across age groups, they recommended cessation of cervical cytology screening for women aged older than 65 years if the following criteria are met:

1) Adequate negative screening (three consecutive negative cytology results or two negative co-tests of cytology plus HPV, within the preceding 10 years and the most recent test occurring within the past five years).

2) No history of CIN 2 or worse in the prior 20 years before exiting screening.

For women who have a history of greater than CIN 2 disease, they should continue screening for at least 20 years after treatment. For women over 65 years, the panel does not recommend reentering screening even in the event of a new sexual partner. Their reason for this is that studies suggest that continued screening beyond age 65 in otherwise low-risk women would prevent only 1.6 per 1,000 cancer cases and 0.5 cancer deaths; in contrast, with continued screening, there would be an additional 127 colposcopies per 1,000 women while extending life expectance by less than one day per woman. A further rationale is that even in the event of a new partner after age 65, and acquiring HPV, most women are likely to have similar rates of viral regression as do younger women and older women have a smaller transformation zone with less susceptibility to HPV infection. In addition, the progression of cervical cancer can be (but not always) 20-25 years.

Commentary: I'm one of those clinicians who continues to perform cervical cancer screening in patients aged older than 65 and very much especially if they have a new male partner. If they have a new partner, I perform co-testing. If they do not, I do a pap smear and HPV test every three years if a history of CIN 1 or less. I also continue to recommend an annual physical and gynecological exam, even if they are asymptomatic, or sexually active. It is however important to appreciate that continued screening comes with risks: Older women have a higher false-positive rate of abnormal cytology--likely due to atrophic and inflammatory changes. As a result, more colposcopies and cervical biopsies may be done but are in fact not necessary. That said, continued screening beyond age 65 years reduces further, albeit an already low incidence of cervical cancer diagnoses.

I choose to do screening in low-risk women, never longer than every three years (not every 5 years), due to data that has emerged since the 2012 guidelines that even in a compliant patient, she has a two-fold increased risk of developing cervical cancer in her lifetime if she does screening based on contesting every 5 years.

Miller T, Flowers L. Navigating the cervical cancer screening guidelines for women aged older than 65 years. Menopause. 2017;24(11): 1302-1303.

Follow-Up of Women with CIN 2

CIN 2 is classified as a high-grade lesion, but even so, most do regress spontaneously, especially in younger women. The optimal follow-up for women with CIN 2 still remains a bit unclear. The current systematic review attempts to better understand the natural history of CIN 2. A total of 36 studies involving 3160 women with CIN 2 and who did not receive treatment, were investigated. At the two-year follow-up, 50% of lesions had regressed, 32% persisted and 18% progressed. For women younger than 30, regression rates were higher at 60%, and persistence was 23%, and progression only 11%. Progression rates were even lower, 5%, in women who were negative for high-risk human papilloma virus 16/18.

Commentary: This systematic review confirms that 50-60% of CIN 2 lesions will regress spontaneously, which means 40-50% will persist or progress. That's too high for my comfort. CIN 2 is a "tweener," you might say, and consists of a range of malignant potential conditions. Unfortunately, we are not yet at the place of fully understanding who will regress, vs who will progress. One sorting-out methodology is to order the HPV subtyping. If 16 and/or 18 positive, that would lead me to more likely treat rather than wait and watch, due to higher risk of progressing. I have developed my own natural medicine protocols for when researched oral alternatives may be adequate, including selenium, folic acid/folate, Coriolus versicolor, indole-3 carbinol, and green tea. In addition, although less researched than the oral, and less researched than the LEEP, topical protocols can include green tea suppositories, or escharotic treatments followed by an herbal vaginal suppository historically called "vag pak." For my comprehensive and current protocols and indications, see the Women's Health Update column in the February/March 2017 issue of Townsend Letter.

Tainio K, et al. Clinical course of untreated cervical intraepithelial neoplasia grade 2 under active surveillance: Systematic review and meta-analysis. BMJ. 2018;Feb 27;360:k499.

Cruickshank M. Treatment or surveillance for CIN 2? Women now have better data on regression and progression to help them decide. BMJ. 2018 Feb 27;360:k771.


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by Tori Hudson, ND
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Author:Hudson, Tori
Publication:Townsend Letter
Date:Aug 1, 2018
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