Novel blood test to detect ovarian cancer at an early stage shows promising results

A new blood test developed by researchers from Adelaide, Australia has the potential to diagnose early and late stage ovarian cancer. The test is engineered from a bacterial toxin and is highly effective in detecting levels of a specific biomarker released in blood by the tumor cells.

With lack of early-stage symptoms and no known definitive screening test, ovarian cancer is difficult to detect at early stages. However, it has a 90% five-year survival rate if detected early as opposed to only 20% five-year survival if detected at the later stages.

The research was published in the November issue of the Journal of Biochemical and Biophysical Research Communications.

Human tumor cells undergo aberrant glycosylation and release N-glycolylneuraminic acid (Neu5Gc)-containing glycans in the bloodstream. The researchers from University of Adelaide and Griffith University noted that a subunit of toxin produced by Shiga toxigenic Escherichia coli recognizes Neu5Gc containing glycans and can be used as a test to detect the abnormal glycans in sera of ovarian cancer patients.

The research team previously used a Neu5Gc-specific lectin, SubB2M, to enhance recognition of Neu5Gc-containing glycans but in the study, they utilized the optical detection technique of surface plasmon resonance (SPR) to detect the binding between SubB2M and Neu5Gc in sera of cancer patients.

In a study involving 69 patients, which included 22 healthy patients and the rest were from all four stages of ovarian cancer, the team showed that Neu5Gc-containing tumor antigens have the potential to serve as diagnostic markers for detection of early-stage ovarian cancer.

Neu5Gc were increased in a majority of stage I/II ovarian cancer and is also uniformly elevated in stage IIIC and IV of ovarian cancer. The test showed a sensitivity of 90% for detection of ovarian cancer for stage I/II, that increased to 100% for stages III and IV of cancer.

“Ovarian cancer is notoriously difficult to detect in its early stages, when there are more options for treatment and survival rates are better. Our new test is, therefore, a potential game changer,” says Professor James Paton, Director of the University of Adelaide’s Research Centre for Infectious Diseases in a media release.

Ovarian cancer is responsible for more cancer deaths than any other cancer of female reproductive tract and ranks fifth in all cancer deaths among women. According to The American Cancer Society, about 22,240 women will receive a new diagnosis of ovarian cancer, and about 14,070 women will die from ovarian cancer in 2018.

The team is currently planning on more extensive studies and looking for commercial partners to bring the test into the market as early as possible.

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Innovative combination of light and ultrasound could help catch ovarian malignancy early

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A team of physicians and researchers from the Washington University School of Medicine in St. Louis has recently developed a ‘hopeful technique’ that combines ultrasound and photoacoustic technology to evaluate and diagnose malignant ovarian tumors at an early stage.

Ovarian malignancies are often diagnosed at a late stage because there are no specific signs and symptoms and no specific screening test for diagnosing ovarian cancer. Only 15% of ovarian cancers are detected at early stages.

The American Cancer Society estimates that about 22,240 women will receive a new diagnosis of ovarian cancer and about 14,070 women will die from ovarian cancer in the year 2018.

The researchers recently conducted a pilot study using co-registered photoacoustic tomography with ultrasound to evaluate ovarian masses in 16 patients at the School of Medicine and Barnes-Jewish Hospital. The results were recently published in the journal Radiology.

The team involving Quing Zhu, professor of biomedical engineering in the School of Engineering & Applied Science created a sheath using optical fibers that encases the standard transvaginal ultrasound probe. The optical fibers are connected with a laser source.

As the sheath is introduced in the vagina, the laser light penetrates the vaginal wall to get absorbed by the tumor to generate sound waves to reveal information about tumor vasculature and sO2 inside the ultrasound visible ovaries.

A normal ovary is not highly vascular and contains a lot of collagen tissue, but a malignant tissue is highly vascular because of neoangiogenesis. Using this multispectral photoacoustic imaging, the team looked at 26 ovarian masses from 16 participants that included nine invasive epithelial ovarian cancers (six serous carcinomas and three endometroid adenocarcinomas), three other tumors (two borderline serous tumors and one sex cord-stromal tumor), and 14 benign and normal (hereafter referred to as benign/normal) ovaries.

The researchers used two biomarkers to study the ovaries: relative total hemoglobin concentration (rHbT), which is directly dependent on the tumor angiogenesis, and mean oxygen saturation (sO2). The rHbT was almost two times higher for invasive epithelial cancerous ovaries as compared to normal ovaries P = .01) and the mean sO2 of invasive epithelial cancers, and the borderline and stromal tumors, was 8.2% lower than that of benign/normal ovaries (P = .003).

“Physicians are very excited about this because it might bring significant change into current clinical practice,” Zhu said. “It is very valuable to detect and diagnose ovarian cancers at early stages. It is also important to provide information and assurance to patients that there is no worry about their ovaries, instead of removing a patient’s ovaries. This technology can also be valuable to monitor high-risk patients who have increased risk of ovarian and breast cancers due to their genetic mutations. The current standard of care for these women is performing risk reduction surgeries to remove their ovaries at some point, which affects their quality of life and causes other health problems.”

Encouraged by the results of the pilot study, the team is gearing up to validate the findings in larger subjects and has applied for funding.

Here is a short video showing Dr. Zhu explaining the technology

Abstract in Radiology Journal

News Release by Washington University in St. Louis

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FDA approves first home-based testing for three BRCA mutations

The US Food and Drug Administration (FDA) has approved the first direct-to-consumer tests for three BRCA1 and BRCA2 gene mutations that are most common in people of Ashkenazi (Eastern European) Jewish descent, but people of other racial and ethnic groups can also have them.

This gives the ability to consumers to order the test directly from home without a consultation or order of healthcare provider.

Women who test positive for any of the three mutations are at increased risk of breast and ovarian cancer and men who test positive are at increased risk of breast cancer. A negative test does not rule out the possibility of the presence of other BRCA mutation which can still put you at increased risk of cancer. There are about 1000 BRCA mutations and the test only detects 3 most common ones.

Absence of BRCA mutation does not also signify that the individual is not at risk of any other type of cancers.

Donald St. Pierre, acting director of the Office of In Vitro Diagnostics and Radiological Health in the FDA’s Center for Devices and Radiological Health said, “This test provides information to certain individuals who may be at increased breast, ovarian or prostate cancer risk and who might not otherwise get genetic screening, and is a step forward in the availability of DTC genetic tests. But it has a lot of caveats.”  in the FDA’s press release.

He warned the consumers that this test should not be a substitute for your screening tests, annual physicals, and consultation with your physician about genetic tests and other lifestyle factors that may influence your risk of developing cancers.

The test results should also not be the sole basis to determine any treatments, including anti-hormone therapies and prophylactic removal of the breasts or ovaries.

After the test results are available, the individual should consult the physician who can request for additional tests and assess your individual risk of getting breast and ovarian cancer. Most cancers are not caused by the mere presence of these mutations, but they are the result of complex interplay between your genes, environment and lifestyle.

The physician will also advise you about ways of reducing the risk of developing cancer.

The FDA granted the marketing authorization to 23andMe, for this test. The company will report the results as a part of its $199 Health and Ancestry product. The consumers who wish to get tested request for a kit that is mailed to them. The saliva samples are collected at home and mailed back in the same kit. Results are ready in 6-8 weeks’ time and can be viewed online by logging into the account.

In April 2017, 23andMe has already received FDA clearance for at home testing of 10 genetic diseases.

Angelina Jolie famously documented her double mastectomy in The New York Times after testing positive for a BRCA mutation and is often held responsible for rising in inappropriate BRCA testing around the world.

In the wake of the announcement by FDA, we are sure to see a rise in the pool of women with BRCA testing.

FDA press release

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Could modified PapTest help detect endometrial and ovarian malignancy?

A new multiplex PCR-based test called PapSEEK was able to detect endometrial and ovarian malignancy from fluid samples collected during routine Pap test, reported Yuxuan Wang, MD, of Johns Hopkins University School of Medicine in Baltimore.

The authors also used a longer sampling brush that sweeps cells from the lining of the uterus called Tao brush, to further increase the sensitivity of detection for the less accessible tumors.

The paper was published in Journal Science Translational Medicine on March 21, 2018, and the study identified endometrial cancer with high sensitivity from samples collected by Pap test and Tao brush, while sensitivity for reporting ovarian cancer was low, but increased when it was combined with DNA testing in the blood samples.

Pap test has been instrumental in bringing down the incidence of cervical cancer by about 60% since its introduction in 1940 but it is not able to detect endometrial and cervical cancers. The researchers at John Hopkins University based this test on the evidence put forth by the previous study published in Journal Science Translational Medicine that both endometrial cancer and ovarian cancer shed cells that collect at the cervix. These cells can be identified by looking for ‘Tumor DNA’ in the samples.

It is to be noted that DNA mutations have already been identified for specific cancers. In the study, the researchers tested for 18 genes common to endometrial and cervical cancer.

The researchers looked at 1915 samples from 1658 individuals, including 656 patients with endometrial or ovarian cancers and 1002 healthy controls.

PapSEEK was used on Pap test samples of 382 women with endometrial cancer, 245 women with ovarian cancer, and 714 women without cancer.

PapSEEK gave a positive result in 81% of endometrial cancer patients, which included 78% of patients with stage I or stage II disease, and 92% of patients with stage III or stage IV disease.

While 33% of Pap test samples were PapSEEK-positive in ovarian cancer patients, including 34% of patients with stage I or stage II disease and 33% of patients with stage III or stage IV disease.

When samples collected by Tao brush was examined, they tested positive in 93% of cases endometrial cancer and 45% cases of ovarian cancer.

The researchers then tested plasma samples from 83 ovarian cancer patients and found that 43% of these patients had detectable circulating tumor DNA. On applying the papSEEK test to the Pap test samples from this group, it was seen that positive results were obtained in 63% of patients.

Currently, there are no screening tests for both endometrial and ovarian cancer and incidence of both is on the rise.  

More than 63,000 women are diagnosed with endometrial cancer in the U.S. each year, and more than 11,000 die each year from the disease. Ovarian cancer is less common but more lethal, affecting more than 22,000 women and killing about 14,000 in the U.S. each year.

Yuxuan Wang, first author on the study said, “Our study demonstrates the ability to detect endometrial and ovarian cancer using cervical fluids obtained using two different methods.”

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Johnson & Johnson to pay $417 million to a ovarian cancer patient: a blockbuster verdict by Jury

In a landmark decision, a jury has ordered Johnson & Johnson (J&J) to pay $417m (£323m) to a woman who claimed she developed ovarian cancer after using the company’s talc-based products such as Johnson’s Baby Powder for feminine hygiene.

The verdict was given in favor of California resident Eva Echeverria,who claimed that she developed terminal cancer after decades of use of J&J’s products.

This is the largest payout yet with J&J facing thousands of lawsuits (4800) for failure to warn the consumer about cancer risk of its talc based products.

“We are grateful for the jury’s verdict on this matter and that Eva Echeverria was able to have her day in court,” said Mark Robinson, her lawyer, in a statement.

Her lawyers argued that the company continued to market and encourage women to use its talc based products, despite aware of its carcinogenic potential.

Earlier, a Missouri jury has awarded $72 million to the family of an Alabama woman who died from ovarian cancer in October 2015.

Despite being named as baby powder, it is used by millions of adults in sensitive area to prevent  chafing or promote dryness.

In its natural form talc contains asbestos, a proven carcinogenic since decades.American Cancer Society states,” When talking about whether or not talcum powder is linked to cancer, it is important to distinguish between talc that contains asbestos and talc that is asbestos-free. Talc that has asbestos is generally accepted as being able to cause cancer if it is inhaled. This type of talc is not used in modern consumer products. The evidence about asbestos-free talc, which is still widely used, is less clear.”

It is postulated that if talc or a product containing talc is applied to your genital area in any way (whether it’s applied directly — what’s called perineal talc use —  or whether it makes its way there via pads, condoms, etc.), the powder particles might be able to travel from your vagina all the way up to your ovaries.

This may set off inflammation, which is believed to play an important role in etiology for ovarian cancer.

Many studies have looked into possible link between talc use and ovarian cancer, but the findings are equivocal. A 2003 meta-analysis of 16 studies (11,933 patients) found a link between talc use and ovarian cancer while a 2014 study of 61,576 women did not find the same link.

Meanwhile J&J said, “We will appeal today’s verdict because we are guided by the science, which supports the safety of Johnson’s baby powder.”

So, the bottom line is we still do not have sufficient evidence to prove causation. FDA states that, “There is not sufficient evidence to prove a possible connection.” However, after a flurry of recent lawsuits The U.S. FDA Office of Women's Health has agreed to fund a study investigating the possible link between cosmetic talc use and ovarian cancer.

A posting on the FDA's website notes that while women are commonly known to use products containing talc for hygiene and cosmetic purposes, talc's effects on the tissues that make up the female genital system have not been adequately investigated.

Till causation is proved, the consumers are advised to play it safe and can use talc free powders. A lot of companies make talc-free baby powder out of cornstarch, including Johnson & Johnson.

Statins in combination with chemotherapy improves survival in ovarian cancer

Women diagnosed with ovarian cancer could survive longer when a statin is added to the treatment regimen, in addition to the cancer-specific treatment says the results of a new research study led by Keele University and published recently in Scientific Reports.

This is in contrast to earlier research studies, in which statins in laboratory studies were effective against ovarian cancer but did not show the same efficacy when tested in real human participants.

Ovarian cancer accounts for only 3 percent of all cancers in women, but it causes more deaths in women than any other reproductive system cancer because it is often diagnosed at a very late stage.

The Centers for Disease Control and Prevention (CDC) estimate that in 2014, 21,161 women in the U.S. found out that they had ovarian cancer and 14,195 died of the disease.

Dr Alan Richardson, a reader in pharmacology in the School of Pharmacy, who led the research at Keele and co-authored the paper, explained:

“We believe we have found the answer to the paradox: for statins to be effective as a cancer therapy, the right statin needs to be used, it needs to be delivered at the right dose and interval, and diet needs to be controlled to reduce sources of geranylgeraniol, which can limit the statin’s effect on cancer cells.”

The researchers at Keele University have identified a particular statin called pitavastatin, which has a long metabolic half-life, necessary for continuous inhibition of tumor growth. It was also seen that diet affects the action of pitavastatin on tumor cells.

The apoptosis of ovarian cancer cells was inhibited in the presence of dietary geranylgeraniol. Geranylgeraniol is present in various foods like sunflower seeds and some varieties of rice.

Statins have shown to be effective in other cancers also. In fact, Pitavastatin was effective in killing cancer cells, even after they have developed drug resistance. This raises the possibility that statins may be useful to treat patients who have developed resistance to chemotherapy.

The inhibitory effect of dietary geranylgeraniol on actions of pitavastatin may explain the discrepancies observed in efficacy of the drug between pre-clincal lab studies and human studies.

The next stage of research is to conduct full clinical trials in humans. Dr Richardson is already planning clinical trials at Keele University. He commented “The key message of our work is that clinical trials of pitavastatin can now be properly designed, and we are in the very early stages of developing trials with our colleagues at Keele University and Birmingham University. It is also noteworthy that pitavastatin is available in a generic form, potentially making this a relatively inexpensive treatment.”

The research also opens new possibilities for use of statins to prevent ovarian cancer. The use of statins in reducing morbidity and mortality in CVDs is well documented. Further targeted clinical trials are needed before it can be clinically prescribed as anticancer.

The Keele University press release can be accessed here.

Full text of the article in Scientific Reports can be accessed here.

The USPSTF maintains its recommendation against screening for ovarian cancer in average risk women

The U.S. Preventive Services Task Force today released a draft recommendation statement and evidence review on ovarian cancer screening that is in line with its final recommendation in 2012.

The USPSTF has given a ‘D’ grade for screening recommendation for ovarian cancer in asymptomatic women, that means “The USPSTF recommends against screening for ovarian cancer in asymptomatic women.”

The USPSTF found adequate evidence that screening with transvaginal ultrasound, testing for the serum tumor marker cancer antigen (CA)–125, or a combination of both does not reduce the number of deaths from ovarian cancer in women.

The current evidence was insufficient to assess the balance of benefits and harms of performing screening pelvic examination in asymptomatic, nonpregnant adult women.

The screening tests also have a low positive predictive value, which means that most women who receive a positive diagnosis of ovarian cancer do not have one.

It also leads to unnecessary surgery and psychological harm.

This screening guidelines are not for women with BRCA 1 and BRCA2 mutation, Lynch, Li-Fraumeni, or Peutz-Jeghers syndrome. Women with BRCA1 and BRCA2 mutations have an average risk of 44% and 17% for developing ovarian cancer. Mutations in BRCA1 and BRCA2 account for around 15 percent of ovarian cancers.

USPSTF also does not advice routine screening in women with family history breast and ovarian cancer, as a higher incidence of cancer incidence in family may results in greater number of patients diagnosed with ovarian cancer but it does not necessary translate into saving lives.

These women can be referred  for genetic counseling and, if indicated, genetic testing.

USPSTF chair David Grossman, MD, MPH, senior investigator at Kaiser Permanente Washington Health Research Institute, said in a statement, “The current screening tests do not do a good job of identifying whether a woman does or does not have ovarian cancer. The Task Force hopes that in the future, better screening tests for ovarian cancer will be developed.”

The draft recommendation was supported by results of two large clinical trials United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) and Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial which both showed that screening for ovarian cancer does not decrease deaths from ovarian cancer in asymptomatic women not known to be at high risk for ovarian cancer.

The recent draft recommendation is in consensus with guidelines issued by other major medical and public health organizations like American College of Obstetricians and Gynecologists, American Cancer Society, American College of Radiology and American Academy of Family Physicians.

The draft recommendation statement is open to public comments till August 14, 2017.

The full text of the recommendations can be accessed here. 

Breast and Ovarian Cancer risk with BRCA mutation precisely quantified for first time.

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Women with BRCA1 and BRCA2 mutations have an average risk of 72% and 69% respectively of developing breast cancer by the age of 80. The corresponding life time risks for ovarian cancer is 44% for BRCA1 and 17% for BRCA2 says the results of first ever prospective study published June 20, 2017 in JAMA.

BRCA1 was first discovered 23 years ago in 1994 by Mary-Claire King, professor of genome sciences and of medicine at University of Washington, BRCA2 followed later.

Today it is an established fact that women who test positive for BRCA mutation are not only at increased risk for breast cancer but also at increased risk for ovarian cancer, but all the studies so far have been retrospective in nature.

According to NIH, together, BRCA1 and BRCA2 mutations account for about 20 to 25 percent of hereditary breast cancers and about 5 to 10 percent of all breast cancers. Similarly, mutations in BRCA1 and BRCA2 account for around 15 percent of ovarian cancers.

This current prospective study was made possible by collaboration between researchers at Australia, Europe and USA. The team recruited 10,000 women with BRCA1(6036) and BRCA2 (3820) mutations from 1997 to 2011 from various registries across U.K, Netherlands and France.

Some very important findings of the study are:

Women with BRCA1 and BRCA2 mutations have an average risk of 72% and 69% respectively of developing breast cancer by the age of 80. The corresponding life time risks for ovarian cancer is 44% for BRCA1 and 17% for BRCA2 

Of nearly 10,000 women, 5046 were unaffected and 4810 were diagnosed with breast or ovarian cancer or both at baseline.

At follow up, 11% of women developed breast cancer, 2% developed ovarian cancer and 11% were affected with contralateral breast cancer.

The median age of women at diagnosis of the breast and ovarian cancer was 38 years and 47 years for contralateral breast cancer.

Another important finding in the study was, breast cancer risk for women with faults in BRCA1 increases till age 40, and for BRCA2 it increases till age 50 years of age and then remains constant high level for the rest of their lives.

The risk of getting a diagnosis of second breast cancer for contralateral breast up to 20 years of first cancer was 40% for BRCA1 carriers and 26% for BRCA2 carriers.

The incidence of ovarian cancer increased with age up to 61 to 70 years for both mutations but was about 3 times higher for BRCA1 carriers.

The risk of breast cancer nearly doubles for both BRCA1 and BRCA2 carriers, with an increase in number of first and second-degree relatives having breast cancer.

The lead author, Antonis Antoniou, PhD, from the Centre for Cancer Genetic Epidemiology, University of Cambridge, United Kingdom explained "This is important information to inform the clinical management also of women with mutations over the age of 60 years old."

The study also revealed that the risk for breast cancer is stratified according to location of the mutation in certain regions, but location did not appear to affect the risk for ovarian cancer.

Dr Antoniou said, "The results from this study show clearly, and again for the first time in a prospective study, that the cancer risks for women with BRCA1 and BRCA2 mutations depend on the position of the specific fault within the gene."

"Moreover, the study provides for the first-time cancer risk estimates for mutations at different locations," he added. "Therefore, mutation location can now be confidently incorporated in the risk assessment of women with BRCA1 and BRCA2 mutations."

http://www.prweb.com

This study has important implications for physicians in clinical practice as they can improve the advice and counselling, precisely pointing at the risk faced by the women. It also emphasizes the importance of family history and following the risk reducing life style changes.

Dr Antonis Antoniou says, "We have been able to provide the most precise estimates of age-specific risks to date. These should provide more confidence in the counseling and clinical management of women with faults in the BRCA1 and BRCA2 genes."

The strengths of the study are its prospective nature, prolong follow-up and large data base because of sharing of data across multiple centers.

Oophorectomy during premenopausal hysterectomy: Evaluating the prevalence

Nearly 1 in 3 women undergo oophorectomy during premenopausal hysterectomy in absence of appropriate indication, reports a study published ahead of print May 8, 2017 in North American Menopausal Society (NAMS) journal Menopause.  

Bilateral Oophorectomy before the age of menopause is associated with increased the risk of parkinsonism, cognitive impairment or dementia, and anxiety or depression. These women, particularly those who were below 45 years at the time of oophorectomy face 67% increase risk of all-cause mortality.

Analysis of data from Nurses’ Health Study also revealed that in 24 years follow up, women who were below 45 years at the time of surgery had 17% increased chances of non-fatal CHD.

In-fact, evidence suggests that at no age, oophorectomy shows any survival benefit.

The current study was a cross sectional analysis of data-base from California Office of Statewide Health Planning Development during a span of 6 years. (2008-2011).

Appropriate indications for oophorectomy with hysterectomy in the study were ovarian cyst, breast cancer susceptibility gene carrier status, and other diagnoses.

A total of 57,776 benign premenopausal hysterectomies with oophorectomies were performed during the 6-year study period.

Out of these 57,776, 21,783 were found to be ‘inappropriate’ as no indication was found among the records.

Through the 6 years of study, the researchers observed a decreasing trend to perform oophorectomy with hysterectomy, but the percentage remain unchanged.

Women with Hispanic and African American ethnicity were more likely to undergo oophorectomy as compared to white women. (P < 0.001).

The authors concluded that, “the rate of inappropriate oophorectomy in California has not changed since the 2008 American College of Obstetricians and Gynecologists guidelines, and over one-third undergo oophorectomy without an appropriate indication documented”.

What does this mean for daily clinical practice?

Prophylactic Hysterectomy should only be done in cases were preponderance of evidence suggests that it will be beneficial to patient.

All patients should be counselled in detail before the surgery regarding the pros and cons of retaining the ovaries at the time of hysterectomy.

ACOG also recommends in favor of retaining normal ovaries in premenopausal women who are not at increased genetic risk of ovarian cancer.

In women with endometriosis, pelvic inflammatory disease, and chronic pelvic pain a decision should be taken after balancing the risk of reoperation vs the benefits of ovarian retention.

ACOG further recommends considering prophylactic salpingectomy in those women who are at population risk for ovarian cancer, and who opt for retention of ovaries.

Today is World Ovarian Cancer day, let’s join in to increase the awareness and save lives.

World Ovarian Cancer day is celebrated on May 8^th each year to save lives by increasing the awareness about this deadly disease.

Ovarian cancer has got the lowest survival rate and often diagnosed at very late stage among all gynecological malignancies. Ovarian Cancer day was first celebrated on May 8th, 2013 when cancer organization all around the world came together to educate the women about symptoms and signs of this malignancy.

Some facts about Ovarian Cancer:

Ovarian cancer is the seventh most common cancer in women worldwide (18 most common cancer overall), with 239,000 new cases diagnosed in 2012.

It is responsible for 140,000 deaths each year. Statistics show that just 45% of women with ovarian cancer are likely to survive for five years compared to up to 89% of women with breast cancer.

Fiji had the highest rate of ovarian cancer, followed by Latvia and Bulgaria.

The five-year prevalence of women globally living with ovarian cancer is 22.6 per 100,000.

Risk factors for developing ovarian cancer:

Age > 55 years, family history, known carrier of abnormalities in the BRCA1 or BRCA2 genes, Nulliparity, never taken the contraceptive pill, long reproductive life span (early menarche and late menopause) and history of endometriosis.

Screening:

There is no “standard” screening test for asymptomatic, low-risk patients, and the only patient populations that should be recommended for ovarian cancer screening are patients with known BRCA germline mutations and women with family members who have had ovarian cancer or breast cancer.

Two common screening tests for high-risk patients include pelvic ultrasound and checking CA 125 levels. But CA 125 is elevated in only 50 percent of stage I ovarian cancers, and many other conditions can falsely elevate the levels, including endometriosis, liver disease and post abdominal surgery. Following a positive screening test, a diagnostic test is required. False positive tests lead to an increase in complications compared to usual follow up. In fact, there are no studies that show screening for ovarian cancer improves survival.

Symptoms:

Ovarian cancer does not have any early symptoms. Often the symptoms are common to other less serious conditions and are often overlooked.

Awareness about risk factors and family/genetic history is the key to clinch the diagnosis at early stage.

If a women experiences following symptoms on most days within a three-week period, she should be investigated: Change in bowel habits, frequent bloating, feeling full very quickly, abdominal or pelvic pain and increased urgency/frequency of urination.

Check out this excellent video by AstraZeneca on World Ovarian Cancer Day.

Oral contraceptive pill use protects against colorectal, endometrial and ovarian cancer.

 courtesy: Getty images

Women who have ever used the ‘pill’ have a decreased chance of having colorectal cancer, endometrial cancer or ovarian cancer than women who had never used the pill according to a new research from The University of Aberdeen, UK

The study was published in February issue of American Journal of Obstetrics and Gynecology.[1]

The study answers three important questions about safety of the use of OC. (1) What is the duration of benefits for endometrial, ovarian, and colorectal cancer. (2) Does combined oral contraceptive use during the reproductive years led to new cancer risks as we age? (3) What is the risk benefit ratio for cancer among past users as they age and enter old age when the general population risk of cancer increases?[2]

This is the longest running study of its kind  that looked at data from 46,022 women who were recruited by the UK Royal College of General Practitioners' Oral Contraception Study in 1968 -1969 and were followed for up to 44 years. The study looked at risk of specific and general cancer risk for women who have ‘ever’ used the pill against the women who have ‘never’ used the pill.

The pill was first approved for contraceptive use in 1960 and was an instant hit with 2.3 million women using it by 1963. Controversies ranged from its inception and are still rife about the pill causing cancers, blood clots, heart attack and stroke.

Few studies have documented that women are protected against GI malignancies and are at increased risk of breast and cervical cancer while currently using pills or being a recent user.

The current study data showed that the protective effect of pill lasts for 30 years even after the pill is stopped and pill users have a 19% lower risk of GI malignancies, 26% lower chance of lymphatic, and hematopoietic cancer, 34% lower risk of endometrial cancer and a 33% lower risk of ovarian cancer.

The study showed a slight increased chance of breast and cervical cancer while using the pill but this was neutralized and plummeted to the general population risk in 5 years of stopping the pill.

The cohort did not show increased risk of any other malignancy as the women aged.

The authors concluded that “Most women who choose to use oral contraceptives do not expose themselves to long-term cancer harms; instead, with some cancers, many women benefit from important reductions of risk that persist for many years after stopping.”

Professor Helen Stokes-Lampard, Chair of the RCGP, said: “Millions of women worldwide who use the combined oral contraceptive pill should be reassured by this comprehensive research that they are not at increased risk of cancer as a result – and that taking the pill might actually decrease their risk of certain cancers.”[3]

“This is not to advocate that women should be given the pill as a preventative measure against cancer as we know that a minority of women do have adverse health effects as a result of taking the pill. Ultimately decisions to prescribe the pill need to be made on a patient by patient basis, but this research will be useful to inform the conversations we have with our patients when discussing various contraceptive options that are available.”

“Long-term and ongoing research into the health effects of any medication is important in shaping new clinical guidelines around the care we are able to provide to our patients – and it’s encouraging to hear that RCGP research that originated in in the 1960s is still having a positive impact and increasing our knowledge now.”

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[1] Iversen L, Sivasubramaniam S, Lee AJ, et al. Lifetime cancer risk and combined oral contraceptives: the Royal College of General Practitioners’ Oral Contraception Study. Am J Obstet Gynecol 2017

[2] http://www.sciencedirect.com/science/article/pii/S0002937817301795

[3] http://www.rcgp.org.uk/news/2017/march/pill-study-should-reassure-millions-of-women-workdwide-says-rcgp.aspx

Douching doubles the risk of developing ovarian cancer.

Clinical pearls:

• Douching and not talc was associated with increased risk of ovarian cancer in the sister study. 
• ACOG and NHS both does not support douching and other vaginal washing practices that do more harm than good by eliminating the healthy vaginal flora. 

A National Health study in US linked the age old ritual of douching to subsequent development of ovarian cancer. Women who douche have nearly twice the risk as compared to women who do not practice it.

According to Department of Health and Human services(HHS) one quarter of women between the ages of 15 and 44 practice douching. [1] Studies have linked douching to Bacterial Vaginosis, Pelvic Inflammatory Disease(PID), STIs, including HIV, preterm birth, ectopic pregnancy and vaginal irritation or dryness. [2] A meta-analysis of more than 10,000 HIV-negative women in sub-Saharan Africa found that intravaginal use of drying agents was associated with an increased risk of BV and HIV.[3] 

American College of Obstetricians and Gynecologists (ACOG) and most practitioners strongly advice against douching and ACOG list it as one of the cause of vaginitis, women continue to practice it because of they see it as a cleaning ritual leading to positive health benefits.[4] The NHS also advise against douching and use of scented wipes and vaginal deodorants.

The new National Institute of Environmental Health Sciences study published online on 20 June,2016 in the Epidemiology Journal recruited 50,884 participants of the “Sister study” and followed them to see the link between douching and ovarian cancer. [5]The sister study is conducted by the National Institute of Environmental Health Sciences of the US Department of Health and Human Services. The study enrolled 50,884 women between ages 35–74 whose sister have breast cancer and followed them from 2003 to 2009, across all 50 US states and Puerto Rico.  Due to the shared environment and genetics, this landmark study provides a great chance of identifying risk factors for breast cancer.

All the women were free of breast or ovarian cancer at baseline. The women were asked about douching and use of talc during the previous 12 months before enrolment.

At the end of the follow up period (median 6.6 years) 154 women were diagnosed with ovarian cancer. Women practicing douching has nearly twice the odds of developing malignancy as compared to women who did not douche. The association looked even stronger when only women without the breast cancer gene in the family were analyzed.

Contrary to previous studies, this particular study did not find any association between talc use and ovarian cancer. (HR=0.73) although talc users were twice as likely to practice douching. (OR=2.1)

This is the first study to trying to find a link between douching and ovarian cancer.

Senior author Clarice Weinberg commented: “There are a number of health reasons not to douche, and I can’t think of any reason to do it.”

Vagina cleans itself naturally and douching cause more harm by cleaning away the healthy bacterial flora. The Office on Women's Health at the U.S. Department of Health and Human Services (HHS) says that due to squirting of the douching solution the bacteria are pushed inside uterus, fallopian tube causing PID.

A study conducted by Brown, J et al in 2016 shows women practice intravaginal washing due to personal hygiene and sexuality. It is common to get cleaned up after or before sex. Majority of these women learn the practices from their mothers or electronic or print media. Many women believe that since departmental stores aisles are packed with these products of personal hygiene, they must be safe to use.

But douching products do not fall under FDA regulation, as they are considered cosmetics. Hence, these products do not have to undergo safety tests like drugs.

The pilot study does not prove causation and larger studies are needed in the area. Perhaps women who douche frequently might have other pathologies going on which may be the cause for the behavior. We need to see more studies in the future. 

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[1]Centers for Disease Control and Prevention. (2013). Key Statistics from the National Survey of Family Growth, 2006–2010.

[2] http://womenshealth.gov/publications/our-publications/fact-sheet/douching.html#

[3] Low N, Chersich MF, Schmidlin K, Egger M, Francis SC, van de Wijgert JH, et al. Intravaginal practices, bacterial vaginosis, and HIV infection in women: individual participant data meta-analysis. PLoS medicine. 2011;8(2):e1000416. 

[4] http://www.acog.org/Patients/FAQs/Vaginitis

[5] http://journals.lww.com/epidem/Abstract/publishahead/Douching,_Talc_Use,_and_Risk_of_Ovarian_Cancer_.98997.aspx