Feature

Cheap and noninvasive: Detecting HPV in sanitary pads


 

A cell phone rings in a red-brick bungalow in a village in India. A woman on the other end of the phone tells Ms. SK, a community health worker, that menstruation has started. Ms. SK guns her scooter through the dusty streets for 15 minutes in 30° C (86° F) heat.

A 32-year-old woman, waiting in the shade of a blue corrugated-iron roof, hands over a green polythene bag. Ms. SK whisks the package to the local health center and tucks it into a –20° C freezer. The following week, it will ride in dry ice to the National Institute for Research in Reproductive and Child Health Laboratory in Mumbai for human papillomavirus (HPV) testing.

The two women are participants in the world’s first community-based validation trial of cervical screening using menstrual pads.

This moment in rural India at first glance appears to have little relevance to wealthy countries such as the United States.

However, public health officials in both countries are trying to solve the same problem: how to prevent unnecessary deaths from cervical cancer by reaching women who have never or rarely been screened.

The United States has more in common with India than it may care to admit.

“In the U.S., we still have pockets of disparities that actually have incidence rates [of cervical cancer] comparable to many low- and middle-income countries,” said Vikrant Sahasrabuddhe, MBBS, DrPh, MPH, of the National Cancer Institute, where he heads the HPV and cervical cancer prevention clinical research program for the National Institutes of Health.

The incidence of cervical cancer in India is approximately 19 per 100,000 women. For the past 15 years incidence in the United States has stalled at approximately 7 per 100,000.

In India, there are no organized screening programs and most cervical cancer is regional or distant metastatic at diagnosis.

In the United States, 52% of new cases are advanced, and half of these are among women who have never or rarely been screened.

“There is a critical need for new strategies to reach this population,” Dr. Sahasrabuddhe said. “We absolutely have to do something out of the box creatively.”

Almost all cervical cancers are triggered by HPV, most commonly high-risk HPV-16 and HPV-18, although there are more than 200 types. HPV testing is taking over from cytology (Papanicolaou test) for secondary prevention of cervical cancer.

The trial of screening for HPV in menstrual pads that is ongoing in India was the brainchild of Atul Budukh, PhD, a government public health researcher and professor at the Centre for Cancer Epidemiology, Tata Memorial Centre, Mumbai.

Dr. Budukh’s eyes were opened to the scale of the problem when he participated in a cluster-randomized trial funded by the Bill and Melinda Gates Foundation. The study, published in 2009 in the New England Journal of Medicine, involved 131,746 rural women in the Osmanabad district of India.

A team of researchers from India and France compared outcomes for women over 8 years after cervical screening by HPV, cytology, or visual inspection with acetic acid. The control group was usual care, where women were advised how to seek screening at local hospitals. Women who screened positive were referred for colposcopy, biopsy, and treatment.

Over the 8-year follow-up, advanced cervical cancer was found in twice as many women left to their own devices, compared with women who had HPV testing during the study (82 vs. 39; hazard ratio for HPV, 0.47; 95% confidence interval, 0.32-0.69).

Similarly, cervical cancer deaths in the control group were nearly two times higher than among the women who were screened for HPV in the study (64 vs. 34; HR for HPV, 0.52; 95% CI, 0.33-0.83).

The study proved that rural Indian women were dying unnecessarily because they weren’t seeking cervical screening. And education wasn’t the problem.

“When we go and educate [a rural woman] about ... risk factors and the need to undergo screening, she understands it very well,” said Dr. Budukh. “She is ready to come but her priority is her bread and butter – she will lose her daily wages.”

Dr. Budukh and his team negotiated with local employers so that women could come to screening clinics, but they soon realized this wasn’t scalable.

One year after the NEJM publication, Dr. Budukh found what he was looking for.

A team of Hong Kong clinicians, headed by Sze Chuen Cesar Wong of the Hong Kong Cancer Institute, published a paper in 2010 in the Journal of Clinical Microbiology showing that menstrual pads provide reliable HPV results in women with and without cervical disease.

The Hong Kong team tested sanitary napkins for HPV from 235 of their patients with cervical intraepithelial neoplasia or condyloma acuminatum before and after treatment. Samples were compared with those from 323 women without cervical disease; for HPV in sanitary napkins the sensitivity was 82.8%, specificity was 93.1%, and positive and negative predictive values were 90% and 87.9%, respectively.

The authors pointed out that menstrual pad testing was the only truly noninvasive approach to HPV screening versus the other self-sampling methods such as tampons and cytobrushes. Also, these self-sampling tests require specialized liquid-based transport media. A menstrual pad needs only a plastic bag.

Dr. Budukh had his at-home solution for the hard-working rural women of India.

With funding from the Indian government, Dr. Budukh’s team put together a validation trial that ran from 2013 to 2016 in 18 rural villages in two separate districts: Ahmednagar and Pune.

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