Vaginal fluid Interleukin-6 seems to be a promising non-invasive marker for the prediction of inflammation in amniotic cavity in PPROM.

Preterm PROM complicates 3% of all pregnancies and is responsible for one third of preterm labors which leads to significant fetal morbidity and mortality. [1]Once the membrane ruptures the protective and sterile environment of the amniotic cavity is breeched linking it to bacterial cervicovaginal flora. This increases the risk of amniochorial infection which in turn is responsible for fetal inflammatory response syndrome.

Obstetricians have to weigh the benefits of prolonging the pregnancy at the risk of intrauterine infection. vs active induction of  labor. Numerous biomarkers have been studied in predicting the occurrence of infection and decide the clinical course of the pregnancy.

Maternal serum markers are not much useful in prediction of the fetal inflammatory response; hence researchers have studied various biomarkers from vaginal fluid like tumor necrosis factor-α, metalloproteinase-8 (MMP-8), soluble HLA-G (sHLA-G) and interleukin-6.

A recent paper published ahead of print in July issue of American Journal of Perinatology concluded that MMP-8, IL-6, glucose, and lactate concentrations in vaginal fluid did predict poor neonatal outcome but it was not reach statistical significance. Only increased levels of metalloproteinase-8 (MMP-8) were associated with poor neurological outcome. [2]

A recent study published in the forthcoming issue of American Journal of Obstetrics and Gynecology aimed to determine the diagnostic indices and predictive value of vaginal fluid interleukin-6 concentration as a point of care tool(POCT) in predicting microbial invasion of the amniotic cavity(MIAC), intra-amniotic inflammation, and microbial-associated intra-amniotic inflammation in patients with preterm PROM.[3]

The researchers also intended to know the relationship between vaginal and amniotic fluid interleukin-6 concentrations in fresh unprocessed samples obtained simultaneously.

This prospective cohort study recruited 153 women with singleton pregnancy who had PROM at between 24+0 and 36+6 weeks. Preterm PROM was confirmed by examination with a sterile speculum to verify the pooling of amniotic fluid in the vagina.

Samples of vaginal and amniotic fluids were collected from posterior fornix and transabdominal. IL6 assessment was done in both fluids by lateral immunoassay.

The cut-off level to define Intra-amniotic inflammation for IL6 was ≥745 pg/mL.

Out of 153 women in the study, samples of vaginal fluid were obtained in 141 women. It was possible to predict the microbial invasion of the amniotic cavity, intra-amniotic inflammation or microbial-associated intra-amniotic inflammation by higher vaginal fluid interleukin-6 concentrations.

The levels of vaginal fluid IL-6 were higher than amniotic fluid IL-6 concentrations.

A IL6 level of ≥2500 pg/mL identified patients with MIAC, intra-amniotic inflammation, and microbial associated intra-amniotic inflammation. Levels of IL6 < 2500 pg/mL could 100 % exclude patients with microbial-associated intra-amniotic inflammation. These findings need future corroboration by larger studies and meta-analysis before a clinical recommendation is made.

This finding has very important clinical implications, because in future it can be used as triage, to decide the expectant vs active management of women with preterm PROM.

By using this easy, cheap, noninvasive and rapid method, women will be spared of the invasive procedure of amniocentesis to evaluate the intrauterine environment.

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[1] http://www.aafp.org/afp/2006/0215/p659.html

[2] http://www.ncbi.nlm.nih.gov/pubmed/27120475

[3] http://www.ajog.org/article/S0002-9378(16)30439-2/abstract

FDA approves Roche’s COBAS HPV Test for use with SurePath Preservative Fluid.

  

The SurePath kit for collecting and transporting the cervical specimens.  

Clinical pearls:

• HPV testing can now be performed on samples collected for liquid based pap test in the BD SurePath preservation fluid using the SurePath vial. 
• Before the approval, healthcare providers have to collect two different samples in two different collecting fluids according to the specification of the testing labs.
• It is not approved as a first line primary screening test.

The U.S. FDA today approved the Roche COBAS test as the first test for Human Papilloma Virus(HPV) from cervical samples collected for Pap Test in BD SurePath Preservative fluid.[1]

COBAS HPV test is a qualitative in vitro test for the detection of Human Papillomavirus in patient specimens. The test utilizes amplification of target DNA by the Polymerase Chain Reaction (PCR) and nucleic acid hybridization for the detection of 14 high-risk (HR) HPV types in a single analysis.

BD SurePath is a liquid based pap test and the test pack includes collection kit, along with storage and transportation components with a vial of preservative liquid.

Some other properties of BD SurePath liquid-based Pap test are ease of transportation, have less than 24% Ethanol which results in immediate and complete cell fixation, preserving the morphology. It also has the ability to preserve the sample for 4 weeks at room temperature, 6 weeks refrigerated.[2]    

The kit comes with specific instructions on how to collect samples to minimize the risks of false negative results.

Till date FDA has not approved any HPV test that can be used with the preservation liquids. Healthcare providers have to collect two different samples, in two different collecting fluids before the announcement was made.

Now, a single sample collected can be used for carrying out both the tests. The test has been approved in women 21 years and more, and helps to determine additional follow-up and diagnostic procedures after ASC-US (Atypical Squamous Cells of Undetermined Significance) Pap cytology results. It has also been approved for use is patients 30 years and older as a primary screening test for HPV along with pap cytology. It detects 14 high-risk HPV types, including HPV 16 and 18, which are responsible for causing 70% of cervical cancer worldwide.

According to the National Cancer Institute, there will be an estimated 12,990 new cases and 4,120 deaths from cervical cancer in the United States during 2016.[3]

"Many labs have a preference in how samples are collected for processing, and this additional approval gives them another clinically validated option for the Cobas HPV test," Uwe Oberlaender, head of Roche Molecular Diagnostics, said in a statement.

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[1] http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm510251.htm

[2] http://www.bd.com/tripath/products/outside_us/outside_us_sp.asp

[3] http://www.cancer.gov/types/cervical/hp

CDC reports a rise in Human papillomavirus(HPV) associated cancers in recent years.

Clinical Pearls:

• HPV associated cancers are on the rise.
• Out of 38,793 HPV-associated cancers diagnosed each year in U.S, nearly 79 % were preventable cancer caused due to HPV strains for which vaccine coverage is available across population.
• Out of all the HPV associated cancer, only cervical cancer is preventable by good screening strategies. No population based screening strategy exist for other HPV associated cancer.

The CDC reported a rise in Human papillomavirus(HPV) associated cancers in recent years’ in its Morbidity and Mortality Weekly Report published on line on July 7, 2016.[1] It is known that HPV is a cause of cervical cancers as well as vulvar, vaginal, oropharyngeal, rectal and anal cancers. 13 known strains of HPV are carcinogenic and persistent infection with these can progress to precancer and cancer.

CDC analyzed the high quality data obtained from population-based cancer registries of National Program of Cancer Registries and the National Cancer Institute’s Surveillance, Epidemiology, and End Results program from 2008–2012, covering approximately 99% of US population.

There was an overall increase in HPV-associated cancer from 10.8 per 100,000 persons during 2004–2008 to 11.7 per 100,000 persons during 2008–2012.

 An average of 38,793 HPV-associated cancers were diagnosed each year during the study span of 5 years. Out of which 23,000 were among females and 15,793 among males. Out of 38,793 at least 30,700(79%) can be attributed to HPV.

Notably, of these 24,600 cancers are attributable to HPV types 16 and 18, which are targeted by all current HPV vaccines, and 28,500 are attributable to high-risk HPV types 31, 33, 45, 52, and 58, all included in the 9-valent HPV vaccine. 

The most common HPV associated cancer was cervical cancer (11,771) in females and oropharyngeal squamous cell carcinomas (15,738) mostly in males.

Only cervical cancer can be prevented with regular screening and follow up, no population based screening strategy exist for other HPV associated cancer. The Healthy People 2020 target for cervical screening is 93%, and the2013 statistics report only 80.7% of women undergo complete screening with wide racial and ethnic disparity.

The authors led by Laura J. Viens, MD, of the Division of Cancer Prevention and Control said “HPV vaccination can prevent infection with HPV types that cause cancer at cervical and other sites," including the anus. "Vaccines are available for HPV types 16 and 18, which cause 63% of all HPV-associated cancers in the United States, and for HPV types 31, 33, 45, 52, and 58, which cause an additional 10%." 

The study has very important public health implication that extending coverage to full US population could prevent future HPV-attributable cancers bringing down the incidence dramatically.

The CDC advisory committee recommends routine HPV vaccination (bivalent, quadrivalent, or 9-valent) for females aged 11-12 through 26 years and quadrivalent or 9-valent for males at ages 11 to 12 through 21 for males if they were not previously vaccinated.

"In order to increase HPV vaccination rates, we must change the perception of the HPV vaccine from something that prevents a sexually transmitted disease to a vaccine that prevents cancer," said Electra Paskett. She is co-director of the Cancer Control Research Program at the Ohio State University Comprehensive Cancer in Columbus.

"Every parent should ask the question: If there was a vaccine I could give my child that would prevent them from developing six different cancers, would I give it to them? The answer would be a resounding yes -- and we would have a dramatic decrease in HPV-related cancers across the globe," Paskett added.

"Ongoing surveillance for HPV-associated cancers using high-quality population-based registries is needed to monitor trends in cancer incidence that might result from increasing use of HPV vaccines and changes in cervical cancer screening practices," the CDC report concluded.

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[1] https://www.cdc.gov/mmwr/volumes/65/wr/mm6526a1.htm?s_cid=mm6526a1_w