One size does not fit all when it comes to sexually transmitted infection (STI) testing. This is especially true because each STI affects populations in different ways, and laboratories need to utilize the right testing methodology to offer the most effective results.
In a recent interview, Salika Shakir, PhD, D(ABMM), medical director, Microbial Amplified Detection at ARUP Laboratories and assistant professor (clinical) at the University of Utah School of Medicine, discussed approaches to STI testing, and how to make sure that the right tests—with proper sample collection—are deployed to all patients.
What technologies does your laboratory use for STI testing?
We use molecular testing for some of the common STIs, including chlamydia, gonorrhea, and Trichomonas vaginalis. We also do PCR testing for Mycoplasma genitalium and other STIs such as HIV, HBV, and HCV, which are screened by serology. We perform HPV testing with a combination of cytologic and molecular testing.
For syphilis, we follow the algorithms outlined by the Centers for Disease Control and Prevention (CDC). We also developed a molecular laboratory test to target those pathogens that cause genital ulcer disease: Treponema pallidum, which is the etiologic agent of syphilis, herpes simplex virus Type 1 and 2, chlamydia L serovars, plus Haemophilus ducreyi, which have low incident rates in the U.S.
How do PCR methods and culture techniques complement each other for diagnosing vaginitis and sexually transmitted infections?
We have molecular tests that are useful for microorganisms that are difficult to culture, such as Chlamydia trachomatis and Mycoplasma genitalium. There are culture-based tests that labs still use for Neisseria gonorrhea.
There are many advantages to molecular testing. They overcome some of the limitations of microscopy and culture-based approaches, can be high-throughput, and they demonstrate increased sensitivity and specificity. They can also detect pathogens even in samples with low bacterial and viral loads from asymptomatic patients. You can use a single sample to test all these different pathogens by targeting their DNA or RNA.
Molecular testing is rapid, and it gives more information from a single patient sample. Most of these tests also give results much faster than traditional methods such as culture. That’s a big advantage because providers are not waiting for those results for several days. Instead, it’s just a few hours.
I know that in some places, culture-based testing is still used for vaginitis, but here we moved ours onto a molecular platform that targets bacterial vaginosis, trichomoniasis, and candidiasis.
How do you approach validating and optimizing the selected targets in a panel for clinical use?
We use clinical samples for validations and verifications, testing first for sensitivity to detect all the different targets in the panel. We also make sure the results are specific to that target, and that there’s no cross reactivity. For example, with the genital ulcer disease panel we created, we wanted to ensure our targets didn’t cross react with other bacterial species, such as skin flora, to avoid false-positive results.
We also make sure our results are reproducible, and test multiple times at an appropriate limit of detection to make sure we get the same result. These are conducted using CLIA regulatory standards.
Can you discuss how the target patient populations might influence the use of panels and how this may impact panel content selection?
There are pathogens that are considered optimal for screening, such as chlamydia and gonorrhea. They can both be asymptomatic, and we have good screening guidelines and recommendations for both men and women. Oftentimes with Chlamydia trachomatis and Neisseria gonorrhea, you can find Trichomonas vaginalis.
Trichomoniasis is one of the most common nonviral STIs. There are no guidelines for routine screening, but there are screening guidelines for those who are considered high risk, such as patients who have multiple sex partners, who have had intercourse with infected individuals, or are on HIV PrEP. Laboratories are not privy to some of that information, but we offer this knowing the prevalence of these pathogens in the community.
Screening recommendations are also patient population-dependent. The guidelines for women who have sex with men, men who have sex with women, and men who have sex with men are all different. Here again, you can have panels where, if it’s an individual vaginal swab test, you can identify Chlamydia trachomatis, Neisseria gonorrhea, Trichomonas vaginalis or Mycoplasma genitalium—all four targets with a single sample.
What should clinicians consider when interpreting results from a molecular panel that includes multiple targets? How do you educate them on this?
As laboratorians, we must work with clinicians to decide what is best for patients, based on what we offer. A lot of it depends on the STI epidemiology, sexual behaviors of the patient population, and who would benefit from screening. We also talk about what samples are appropriate for screening or testing, and how they should be collected. We’re helping them understand one size doesn’t fit all.
Explain the importance of sample type and how the lab can work with clinicians to optimize this.
This is an important opportunity for education. For example, we provide information through test directory and consultative services. We have information on our landing pages and lectures to explain the CDC’s most up-to-date recommendations for screening and testing.
That includes which swabs are optimal. A study just came out this year showing that using urine instead of vaginal-swab testing could result in 400,000 missed STI cases each year (Ann Fam Med 2023; doi: 10.1370/afm.2942). That’s a big deal.
We tell our clinicians that if an individual with a vagina walks into a clinic, the best type of sample would be a vaginal swab. We help them understand that not all samples are equal, and that sometimes an individual needs multiple swabs taken, depending on their exposures, sexual activity, and anatomy.
Can you share your experience with reimbursement for panel testing, multiple target testing?
It’s always a big question for payers to reimburse panel testing, especially when there are multiple targets. Data is still being generated for panels with more than five targets and whether those are clinically useful.
Sometime ago, we ran into this issue when we first offered a vaginitis panel molecular test. There was concern about reimbursement, but soon after, the Centers for Medicare and Medicaid Services and most of the other large payers said it was reasonable to perform targeted or expanded panels for vaginitis.
Looking ahead, what do you see as important areas of ongoing research and development in molecular testing for STDs?
Having easy access to, and more cost effective, rapid point-of-care (POC) testing will be useful. There are some FDA-cleared or CLIA-waived test sets available, but they’re not widespread, and the cost of the assays can be prohibitive.
There is also a social stigma associated with STI testing, and it can be hard to get a patient back into the office—an important reason POC tests are helpful. If the patients could wait for results, clinicians could send them home with the right antibiotic therapy. It would improve patient screening overall.
I’m also really interested in self-collection for STI testing. There are FDA-cleared assays that have self-collected vaginal swabs approved for testing in the clinician’s office setting where, of course, urine is sort of self-collected. There are also studies to show rectal and throat self-collection can be done, and is even preferred, because it has been shown to result in great patient satisfaction, if you provide good collection instructions.
If anything, the pandemic has shown us that we can do this. When we were going through the COVID-19 pandemic, and STI clinics had to shut down and direct those resources to COVID testing, many healthcare clinics didn’t have providers who were able to collect specimens, so self-collection became an acceptable method.
There also have been new studies about self-testing and home-based testing. That’s something for us to look out for. Providers and laboratories must be involved to ensure high quality testing, but I see great potential there for improving population health.
Jen A. Miller is a freelance journalist who lives in Audubon, New Jersey. Twitter:@byJenAMiller