There is an appreciable number of available, high-quality certification programs that focus on digital investigations and forensics. However, there are also many certifications and programs in this area that are far less transparent and widely known.

There’s been a steady demand for digital forensics certifications for the past several years, mainly owing to the following:

• Computer crime continues to escalate. As more cybercrimes are reported, more investigations and qualified investigators are needed. This is good news for law enforcement and private investigators who specialize in digital forensics.
• There’s high demand for qualified digital forensics professionals because nearly every police department needs trained candidates with suitable credentials.
• IT professionals interested in working for the federal government (either as full-time employees or private contractors) must meet certain minimum training standards in information security. Digital forensics qualifies as part of the mix needed to meet them, which further adds to the demand for certified digital forensics professionals.

As a result, there is a continuing rise of companies that offer digital forensics training and certifications. Alas, many of these are “private label” credentials that are not well recognized. Making sense of all options and finding the right certification for you may be trickier than it seems.

To help choose our top five certifications for 2019, we looked at several popular online job boards to determine the number of advertised positions that require these certifications. While the genuine results vary from day to day and by job board, this should supply you an idea of the number of digital forensic jobs with specific certification requirements.

Stability is defined as “the extent to which a product retains, within specified limits and throughout its period of storage and use (i.e., its shelf life), the same properties and characteristics that it possessed at the time of manufacture.”¹ According to FDA regulations, IVD reagents and consumables marketed in the U.S. must undergo testing to determine stability.

The regulatory requirements for stability testing of IVDs are found in several places. For example, the Code of Federal Regulations (CFR) states that “the basis for such instructions (e.g., those needed to protect the stability of the product) shall be determined by reliable, meaningful, and specific test methods.”² IVDs approved by the Center for Biologics Evaluation and Research (CBER) are also subject to other CFR requirements, which state that an application for a biological license shall include “data establishing stability of the product through the dating period.”³

While a significant number of guidance documents directly relate to the requirements for stability testing of drugs, guidance regarding stability testing of medical devices in general and IVDs in particular is limited.^{1, 4, 5, 6} This article discusses the various aspects unique to stability testing of IVDs and offers suggestions on how to optimize the design of stability studies. This article also discusses effective responses to stability issues as they arise.

Design Control Elements

For new IVDs, manufacturers should first address stability requirements during the design control stage. At this stage, IVD manufacturers should determine the device’s intended use and the critical design components that must be evaluated to assure that the labeled expiration dates are met. Manufacturers should also consider user requirements and their impact on stability. IVD manufacturers should focus on user needs regarding product stability such as the following:

• Onboard stability (e.g., the maximum length of time IVDs can be loaded onto an instrument and still perform according to specifications). Shortened onboard stability requires more user intervention to replace reagents and creates delays in work output.
• Labeled storage conditions. IVDs with multiple storage conditions, such as six months frozen or 24 hours thawed, require more user interaction, which could lead to errors when trying to establish the “after opening/thawing” expiration. 
• Preservative effectiveness for microbially controlled or sterile IVDs. The use of a preservative should control microbial growth in situations in which the user opens the device packaging multiple times during the product’s life. For many IVDs, microbial contamination can result in IVD performance issues due to microbial metabolism.

The user requirements related to stability are established as design inputs and are ultimately assessed during stability studies. 

Using Accelerated Study Data

Accelerated stability studies are useful for predicting the shelf life of IVDs. Such accelerated studies subject IVDs to extreme conditions—typically elevated temperatures—to the extent that the device endures significant and measurable deterioration during the testing period. Mathematical extrapolations, such as the Arrhenius equation, are then used to calculate the IVD’s predicted shelf life.⁴ However, not all IVDs follow a predictable degradation rate. Some products will perform acceptably until they fail, in which case only real-time testing will suffice.

According to FDA’s Office of In Vitro Diagnostic Device Evaluation and Safety, accelerated stability studies are acceptable in the following situations:

• Establishing preliminary claims in new products only if there is sufficient correlation to an existing product.
• Supporting implementation of a change to an existing product.

The Center for Devices and Radiological Health (CDRH) recognizes the European standard EN 13640:2000, which provides guidance on not only conducting real-time and accelerated stability studies but also making calculations using the Arrhenius equation.⁷ Typically, CDRH requires premarket notification (510(k)) submissions to include a summary of the accelerated data, while premarket approval (PMA) submissions are expected to include the real-time study data and stability protocol. At the same time, CBER does not accept accelerated testing for either newly licensed IVDs or changes to existing IVDs. Only real-time stability data are accepted; they are also required for biologics license application (BLA) submissions, in which labeled storage and reconstituted stability data should be included.⁶

Overall, FDA expects all accelerated studies to be confirmed with real-time stability studies.⁴ However, prior to using accelerated data to support new IVDs or a significant change to existing IVDs, manufacturers should confer with the proper center at FDA about the agency’s requirements regarding stability studies for specific IVD reagents. 

Real-Time Stability Study Requirements

A real-time stability study includes an evaluation of those factors that ultimately affect the expiration date of IVD reagents. A number of IVD reagent stability factors should be considered when designing a stability study program (see Table I).^{1, 4, 5, 6}

While originally established as a design verification requirement, a stability study for IVD reagents has the same elements as those dictated for stability testing of drugs including the following:

• A written stability testing program designed to assess the stability characteristics of IVDs.
• A stability protocol with predefined acceptance criteria that can be correlated to the label claims. 
• Testing multiple unique product lots. A stability study is required to use three product lots that are manufactured when the manufacturing process has been well defined and can be consistently executed.
• Evaluation of each stability attribute via a statistically valid trial size and testing intervals. The trial size should be sufficient to overcome the precision of the test method used, considering the cumulative effect of all elements of the test system (i.e., individual reagents and instruments). The test intervals should be chosen so that trends may be discerned from variability of the data.4 At a minimum, stability testing should continue to one time interval past labeled expiration.
• Control of material storage. For real-time stability testing, the IVD reagents should be stored under the conditions stated on the label (e.g., temperature, humidity, light protection). 
• Testing IVDs in the same container-closure system as the marketed product.
• For IVDs that require reconstitution for use as directed in the labeling, testing IVDs for reconstitution as well as after they are reconstituted.
• Use of reliable, meaningful, and specific test methods.⁸ 

This last requirement presents the greatest challenge to the design of IVD stability studies. While stability testing of drugs is accomplished through direct analytical testing of the drug itself, the typical evaluation of IVD stability involves performing the assay and determining whether the control values conform to the specifications. This technique is used regardless of the IVD component being evaluated for stability: reagent, calibrator, or control. To allow for adequate evaluation of the IVD components for stability, manufacturers should identify the control criteria for their particular system to detect and reduce the bias effect of the test system as a whole. These control criteria should consider the effects that changes in instruments, reagents, calibrators, or controls may have on the test system.

Monitoring Bias

There is a potential for failure to control the effects of bias on stability results (see Figure 1). For illustration purposes, assume the IVD component being tested for stability is a control and the acceptance criteria are such that when the assay is performed in accordance with the labeling instructions, a control value is obtained that meets the label claims. In Figure 1, the value at T3 reflects a change in the reference reagent lot used during stability testing, which introduces a bias into the stability degradation pattern. The net effect is a downward shift in the control value, thus giving more time until genuine stability failure. 

One method to monitor for bias is conducting parallel testing when new reference materials are introduced into a stability study. Stringent criteria should be created to assess the effects that changes in reference materials have on the stability profile. These criteria should consider the inherent variations in the test system itself, including the variation contributed by each IVD assay component as well as the instrument. Comparing the values obtained by the original reference materials with the new reference materials will detect the introduction of bias created by the new reference materials. Any shift in assay values that is outside the expected precision of the test system should prompt an investigation.

Another effective control mechanism to evaluate stability data is conducting a linear regression analysis to detect changes in the slope of the stability degradation pattern for each lot. This technique offers two unique opportunities for evaluating data:

• Detecting changes in the slope within the stability data obtained for a single lot may indicate that bias could have been introduced into the test system, which creates the potential for inaccuracy in evaluating the data.
• A regression analysis of stability data allows an estimation of time until stability failure, thereby allowing a more timely response to stability issues.

Ongoing Stability Study Monitoring

Once the stability studies necessary to support the labeled expiration date of a newly designed IVD have been completed, manufacturers must then address the need for postapproval or ongoing stability studies.

Unless stipulated as a postapproval requirement, FDA does not explicitly require ongoing, or postapproval, stability study monitoring for IVDs. An FDA compliance policy guide (CPG) states that CBER-licensed IVDs generally are not required to conduct postapproval stability studies, with certain exceptions.⁵ While this CPG does not include CDRH-regulated IVDs within its scope, the scientific rationale regarding the need for postapproval studies in certain situations still applies; as such, CDRH-regulated IVDs should follow the same guidance. 

According to the CPG, FDA investigators will cite CBER-licensed IVD manufacturers for not performing postapproval stability studies when:

• Performing the postapproval studies is required as a condition of the license.
• A formulation or manufacturing change has been made.
• There is a commitment to perform postapproval stability studies as part of a corrective and preventive action plan.⁵

Despite the limited requirements for postapproval stability studies as set forth in the CPG, ongoing stability studies are a useful and critical element of process monitoring as dictated by the CFR. One section states that, “manufacturers shall monitor production processes to ensure that a device conforms to its specifications.9 Another CFR section states that manufacturers shall analyze “quality data to identify existing and potential nonconforming product, or other quality problems.”9 It is up to IVD manufacturers to evaluate and determine the need for and extent of ongoing stability monitoring, taking into consideration the risk associated with the IVD reagent as well as regulatory commitments and requirements.4 Manufacturers should be prepared to discuss with FDA the scientific rationale behind their stability study programs, including both preapproval and postapproval study designs. 

Investigating Stability Failures

Once a potential stability issue has been detected during either premarket or postmarket stability studies, IVD manufacturers should initiate a timely and thorough failure investigation. In most cases, manufacturers have already released for distribution the product lots with stability issues. Nonetheless, an investigation must proceed with the knowledge that stability failures on distributed products represent a high regulatory and patient-care risk. 

Stability failure investigations should include an impact analysis to determine the scope of product lots potentially affected by the problem. IVD manufacturers should place all lots on hold until they determine the scope of the stability issue. Manufacturers should report any immediate action taken to control nonconforming products, such as recalls, corrections, or removals, to FDA as required in accordance with the regulations.^{9, 10}

IVD manufacturers can identify the product lots at risk for premature stability failure by using various techniques, including statistical tools, prior to determining the root causes. For example, assume a stability failure has occurred prior to the labeled expiration date. For purposes of this example, the decay rate for the lots at risk for stability failure is calculated to be 20 ng/ml/month, which is significantly higher than what is typically seen for this IVD. 

Through linear regression and by using the upper stability specification limit at expiration, a model can be created to determine the release specification range that is most likely to fail to meet the labeled expiration date. By determining this specification at the point that intercepts the y-axis, this minimum value can then be compared with the release date for previous product lots to determine the lots most susceptible to stability failure (see Figure 2). 

A root cause analysis should focus on the variables that could potentially affect product stability. Primary suspects are raw materials and manufacturing changes. For temperature-sensitive products, IVD manufacturers should examine product temperature control during manufacturing and handling. Manufacturers should also look at manufacturing activities that subject raw materials or in-process products to elevated temperatures (e.g., outside of labeled storage conditions) for any period of time, including time spent in thawing or adjusting materials to hit the target potency.

Once IVD manufacturers identify the root causes, appropriate global corrective actions must be assigned and implemented. For example, issues with raw material control may result in additional specifications. Identifying adequate corrective actions must also consider the potential gaps in the manufacturer’s quality system that allowed the stability failure to occur. For example, design issues may not have adequately addressed raw material control. In addition to a raw-material specification change, the proper corrective action in this case would be to modify the design control process to include the knowledge gained from the stability failure.

After implementing the corrective actions, an evaluation of the effectiveness of the corrective actions should be conducted through verification and/or validation activities. For stability issues, this would involve activities such as placing additional product lots manufactured after the corrective action into the stability program and potentially adding test intervals to better monitor the product and/or degradation rate. The success of the corrective actions should be directly measurable. In other words, to say the measure of success of the corrective actions is that no more lots will fail stability is not adequate. The simple reason is that it would take a stability failure that equates to nonconforming products in the field to prove the corrective action was not adequate.

Conclusion

Meeting the regulatory requirements regarding stability testing of IVDs represents a challenge to IVD manufacturers. Manufacturers must consider special considerations unique to IVDs to assure that the stability study design provides accurate data to support labeled product expiration dates. A robust IVD stability program initiated as early as possible during product development, in conjunction with prompt and thorough responses to identified stability issues, assures that IVDs will continue to meet the user needs throughout their labeled expiration. 

References
1. Shelf Life of Medical Devices (Rockville, MD: Division of Small Manufacturers Assistance, Center for Devices and Radiological Health, 1991).

2. “In Vitro Diagnostics for Human Use,” Code of Federal Regulations, 21 CFR Part 809.

3. “Licensing,” Code of Federal Regulations, 21 CFR Part 601.

4. Stability Testing of In Vitro Diagnostic Reagents, EN 13640:2002 (Brussels: European Committee for Standardization, 2001).

5. Section 280.100, “Stability Requirements for Licensed In Vitro Diagnostic Products,” Compliance Policy Guide (Rockville, MD: Office of Regulatory Affairs, U.S. Food and Drug Administration, 2000).

6. Guideline for the Manufacture of In Vitro Diagnostic Products (Rockville, MD: Office of Compliance, Center for Devices and Radiological Health, 1994).

7. IVD Standards Web Page (Rockville, MD: Office of In Vitro Diagnostic Device Evaluation and Safety, Center for Devices and Radiological Health, 2004 [cited 19 January 2004]); available from Internet: CLICK HERE.   

8. “CGMP for the Manufacture, Processing, Packing, or Holding of Drugs and Finished Pharmaceuticals,” Code of Federal Regulations, 21 CFR Part 211.

9. “Quality Systems Regulation,” Code of Federal Regulations, 21 CFR Part 820.

10. “Medical Devices; Reports of Corrections and Removals,” Code of Federal Regulations, 21 CFR Part 806.   

Copyright ©2004 IVD Technology

Photo: istockphoto.com

Household pollutants can come from a variety of sources including the materials used in your home’s construction, and mold and mildew caused by poor ventilation. Clean air in the home can protect you from carcinogens, allergens, and harmful particulates. Even if you don’t suspect a problem, it’s a good idea to have some type of air quality monitor in the home. Threats like radon and carbon monoxide are colorless, odorless, and tasteless, and you’ll have no clue that there’s trouble until you’re already in the danger zone. The good news is that it’s fairly easy to conduct indoor air quality testing and monitoring yourself: All you need is a few key tools.

Signs of Poor Indoor Air Quality

The wide range of pollutants, particulates, and allergens that can affect indoor air make it difficult to create an all-inclusive list of poor indoor air quality indicators. However, there are circumstances and signs that could indicate poor air quality in your home, including:

• Poor ventilation: Condensation on walls or windows, musty-smelling air, or areas where mold collects on walls suggests a ventilation issue.
• Health problems: Respiratory or other health problems that develop after moving into a home and that subside after time spent away from home point toward an environmental issue in the home.
• Unusual odors: If you notice unusual odors after a period of absence from home, pollutants or mold could be permeating the indoor air.
• Older homes: Materials and construction methods used in older homes sometimes include materials known to emit harmful VOCs or pollutants. Outdated construction methods may also contribute to ventilation problems. That doesn’t mean that new homes can’t have issues with indoor air quality—it just means that poor indoor air quality is less likely in newer builds because they have to conform to modern building codes.

RELATED: Mold vs. Mildew: What’s the Difference?

Before You Begin

Not every home requires air quality testing for every potential particulate or pollutant. Often, the types of symptoms you experience and the age and location of the home can help you narrow down potential pollutants. Be sure to consult a doctor if you are experiencing health problems that you suspect are related to your home environment. A doctor can help identify and treat health issues related to exposure to mold, radon, and carbon monoxide.

STEP 1: Set up an indoor air quality monitor.

How is air quality measured? Some monitors use electrochemical sensors that detect toxins while others estimate particulate matter (PM) based on the particulates that pass in front of a laser. It depends on the type of monitor you have and what it’s designed to detect.

Air quality testing can detect harmful odorless gasses like carbon monoxide and radon. Depending on the model, they may also detect volatile organic compounds (VOCs) or pollutants such as airborne particulate matter. More advanced indoor air quality monitors may also measure the room’s humidity and temperature.

Choose a monitor that detects the specific pollutants that concern you. For example, if you live in an area with high air pollution, you’re more likely to need a model that detects particulate matter. Those who live in older homes may want to get a model that detects radon and carbon monoxide (though either can be present in newer homes, too).

Our Recommendation: Temptop M10 Air Quality Monitor – Get it at Amazon for $92.99
This portable air quality monitor’s sensors track airborne particulate matter, VOCs, and formaldehyde with a simple display and interface.

STEP 2: Test for mold.

Mold tests come in various formats, including swabs, tape strips, air pumps, and petri dish tests. Swabs and tape strip tests collect potential contaminants from a surface like a counter or tabletop. The results from a swab test come within a few minutes, though you may not know the exact type of mold.

Tape strips, air pumps, and petri dish tests require the collected trial be sent to a lab for analysis. While these tests are more accurate than a simple swab test, it can take anywhere from a few days to a few weeks to get the results. Additionally, petri dish tests can get contaminated from other particles in the air. Tape strips and swabs can also get contaminated by other particles on the tested surface.

Air pumps offer a closed system that’s less likely to get contaminated, though they tend to cost more. Set the mold test up near the home’s ventilation or in the area where you suspect mold or a contaminant. However, always follow the directions on the test kit for the best results.

Our Recommendation: Seeml Labs DIY Mold 3 Test Kit – Get it at Amazon for $32.99 
This kit comes with three tests (one swab and two tape strips), which offer same-day (that the results arrive) results from a lab.

RELATED: How to Test for Mold

STEP 3: Perform a radon test at home.

Radon gas naturally occurs as a byproduct of the breakdown of the uranium found in certain rocks and soil. The gas can seep its way into a home through the foundation until it reaches harmful levels.

Radon tests detect levels of the gas over time. Short-term tests take 90 days or less, while long-term tests can take several months. The results from these tests are usually interpreted by a lab. Continuous tests monitor radon levels at all times and alert you if high levels of radon are detected.

Depending on the type of radon test you use, the testing process may require installing detection sheets or other materials in an area suggested by the manufacturer. The key is to follow the instructions on the test.

Our Recommendation: Airthings 2989 View Radon – Get it at Amazon for $199.99
This continuous, battery- or USB-operated radon monitor measures indoor radon levels, temperature, and humidity and integrates with the Airthings mobile app to provide the user remote alerts.

STEP 4: Install carbon monoxide detectors on every level of your home.

Carbon monoxide (CO) is an odorless, poisonous gas that causes confusion, dizziness, and headaches before it causes a loss of consciousness and death. Many smoke detectors these days are combination smoke and carbon monoxide detectors. It’s critically important to have both types of detectors in your home, so you’ll want to make sure that your home safety plan monitors both smoke and carbon monoxide.

Carbon monoxide detectors should be placed outside bedrooms, and anywhere in the house you’d place a smoke detectors. There should be a carbon monoxide detector on each level of the home and near sleeping areas. Carbon monoxide rises with air, so the detector should be placed about 5 feet off the floor on a wall or on the ceiling. Do not put them near a fireplace or open flame.

Our Recommendation: Kidde Nighthawk Carbon Monoxide Detector – Get it at Amazon for $34.99
Kidde’s Nighthawk is a reliable, affordable carbon monoxide detector that sounds when CO levels reach unhealthy levels. We like that it has a digital display and multiple power sources, including battery backup, so it will continue functioning during a power outage.

RELATED: 8 Myths About Indoor Air Quality and the Facts You Need to Breathe Easy

Tips for Improving Indoor Air Quality

Home air quality monitoring devices will alert you if pollutants reach dangerous levels. However, there are many things you can do to prevent levels from reaching dangerous levels in the first place.

• Check your HVAC system to make sure it’s functioning at peak efficiency.

• Increase the airflow in your home by periodically opening the windows and using fans to circulate the air.

• Stay on top of mold removal and prevention around the home. If you find mold, try scrubbing it with a mold-killing cleaner like bleach or borax. For delicate surfaces, you can use dish soap or diluted white vinegar. Unfortunately, you may not be able to remove mold from porous surfaces, and they may need to be replaced.

Carbon monoxide is incredibly dangerous. If you suspect that there’s carbon monoxide in your home in high or low doses, leave at once. Open windows and doors, and get outside into the fresh air. Contact the proper authorities to get you and the home checked for carbon monoxide poisoning.

Prices in this article are accurate as of August 3, 2023.

At-home DNA test kits can help you uncover and explore your genetic origins and connect with long-lost relatives, all from the comfort of home. Here are our top-rated ancestry DNA kits for 2023.

Finding out about your heritage through at-home DNA testing has become a popular American pastime. In fact, according to one forecast, the DNA testing market generated more than $487 million in revenue in 2019, and projections for 2026 push those numbers even higher^[1].

How Do At-Home DNA Kits Work?

Most at-home DNA testing kits use saliva and provide a collection kit. Once you send your collection kit back to the company, they will likely either send it to a third-party lab or their own lab, and analyze your DNA from the cells in your saliva.

Lab technicians analyze specific genetic markers in your DNA that are common in certain regions and ethnic backgrounds, which helps you to see where your ancestors are most likely from, and if there are other people in their databases who share certain specific genetic markers as well.

Most At-Home DNA ancestry kits also provide a full spectrum of online ancestry and heritage research tools to help you build a family tree, explore your DNA-based origins and connect with potential relatives worldwide.

Are Home DNA Kits Accurate?

Health professionals caution against using at-home DNA testing that focuses on health and certain predispositions for some diseases. This is because at-home health tests only look at certain DNA markers, not the whole sequence. Think of it as a more zoomed out version of the results you would get from a doctor-ordered, geneticist-analyzed test. Indeed, the Centers for Disease Control and Prevention has cautioned that personal genomic tests are not diagnostic tests, and should not be used alone for treatment decisions or medical interventions.

These zoomed-out results are more accepted for DNA-backed ancestry kits since they are designed to only analyze common genetic markers across populations for origin tracing.

Sources

Footnotes

1. World Consumer DNA (Genetic) Testing Market Report 2021. Globenewswire. Accessed 8/3/2022.

References

• Direct to Consumer Genetic Testing: Think Before You Spit, 2017 Edition. Centers for Disease Control and Prevention. Accessed 8/9/2022.

Is your glass half-full or half-empty? On those days when nothing in your life seems to be going right, it can be really tough to see the silver lining among all those clouds. However, it's during these times when the ability to see the good in even the worst situations is so important. An optimistic attitude benefits not only your mental health, but your physical well-being as well. Take this test to see where you fall on the optimism/pessimism continuum.

This test is made up of two types of questions: scenarios and self-assessment. For each scenario, answer according to how you would most likely behave in a similar situation. For the self-assessment questions, indicate the extent to which you agree with the given statements. In order to receive the most accurate results, please answer each question as honestly as possible.

This test is intended for informational and entertainment purposes only. It is not a substitute for professional diagnosis or for the treatment of any health condition. If you would like to seek the advice of a licensed mental health professional you can search Psychology Today's directory here.

Abstract and Introduction

Abstract

Human papillomavirus (HPV) is necessary for the development of cervical carcinoma, and incorporation of molecular testing for HPV in screening and patient management has been proposed. Sufficient scientific evidence exists to recommend HPV DNA testing in the triage of women with equivocal cytology and in follow-up after the treatment of precursor lesions. However, due to a low clinical specificity and positive predictive value, HPV DNA testing has so far not been recommended as primary screening in Europe. In general, diagnostic HPV tests have to demonstrate accuracy, reproducibility and clinical utility before they can be used in patient management and implemented in cervical cancer screening programmes. In this article we supply an overview of RNA-based HPV diagnostics and the role of E6/E7 mRNA detection as a predictive marker for the development of cervical carcinoma. HPV E6/E7 mRNA testing for high-risk types seems to correlate better with the severity of the lesion compared with HPV DNA testing, and is a potential marker for the identification of women at risk of developing cervical carcinoma. Commercial assays for simultaneous genotyping and detection of E6/E7 mRNA from the five most common high-risk HPV types are now available and require further evaluation for primary screening, triage and follow-up after treatment.

Introduction

Cervical cancer is the second most common cancer among women worldwide with approximately 493,000 new cases and 274,000 deaths in 2002.^[1] The majority of cases appear between the ages of 30 and 50 years when women are actively involved in their careers and caring for their families. Consequently, the total years-of-life lost is much higher than for other female cancers, which have a later age of onset. Some types of human papillomavirus (HPV) have been established as the central cause of cervical carcinoma.^[2,3,4] Both premalignant and malignant epithelial lesions of the cervix are associated with HPV (Figure 1).

HPV is the most common sexually transmitted infection among men and women, and it has been estimated that 70% of sexually active women will acquire an HPV infection at some point during their lifetime.^[5] More than 100 different genotypes have been isolated, and at least 40 infect the epithelial lining of the anogenital and aerodigestive tract.^[6] Based upon epidemiologic studies, HPV viruses are classified as high-risk, probably high-risk and low-risk types ( Table 1 ).^[7] Persistent infection with one of the high-risk types is the first step in carcinogenesis.^[8] The vast majority of HPV infections are asymptomatic and transient, especially in the young population, and more than 90% of new infections will resolve within 2 years.^[9] It is not clearly understood, however, why HPV infections resolve in certain individuals, but result in high-grade cervical neoplasia in others.^[10] Several viral and host factors are thought to play a role in cervical carcinogenesis. Established cofactors are smoking, long-term oral contraceptive use, HIV co-infection and high parity, while HSV-2, Chlamydia trachomatis, immunosuppression, diet and nutrition are probable cofactors.^[2] Worldwide, pooled data from case-control studies indicate that HPV DNA can be detected in 99.7% of women with histo ogically confirmed squamous cell carcinoma and in 13.4% of control women with normal cytology.^[2]

HPVs are small, non-enveloped DNA viruses, approximately 55 nm in diameter, that infect basal cells and replicate in the nucleus of squamous epithelial cells. The genomic organization of each of the papillomaviruses is remarkably similar and can be divided into three functional regions (Figure 2). Following infection, the early HPV genes (E6, E7, E1, E2, E4 and E5) are expressed and the viral DNA replicates from the episomal form of the virus. In the upper layer of the epithelium the viral genome is replicated further, and the late genes (L1 and L2) and E4 are expressed (Figure 3). The shed virus can then initiate new infections. Low-grade intraepithelial lesions support productive viral replication. Progression to high-grade intraepithelial lesions and invasive carcinomas is associated with a persistent high-risk HPV infection and integration of the HPV genome into the host chromosomes, loss or disruption of E2 and subsequent upregulation of E6 and E7 expression (Figure 3).^[8,10,11] E6 and E7 are the oncogenes of the virus and expression of these genes is required for malignant transformation. Among others, E6 and E7 mediate degradation of the tumor suppressors p53 and RB, respectively, and interfere with cell-cycle regulation.^[8,10] E6 and E7 proteins from low-risk types are less competent in interfering with p53 and pRb functions than E6/E7 proteins from high-risk types.^[12,13] Therefore, low-risk HPV infections are associated with benign proliferations, such as genital warts and low-grade intraepithelial lesions prone to regress.

You should wait to take a pregnancy test until the first day of your missed period. Since HCG is only present once implantation of the egg occurs, there often isn’t enough of the hormone to be detected until you miss your menstrual cycle.

“Pregnancy tests pick up the hormone secreted after implantation, which usually occurs about two weeks after the sperm meets the egg,” says Dr. Culwell. “For women who have regular periods, this usually means that HCG can be detected as soon as you miss a period.”

This, of course, assumes you have a regular menstrual cycle that can be easily tracked and predicted. If this isn’t the case, you may choose to instead track ovulation, or when an egg is released and makes its way to the uterus where it can potentially be fertilized. An at-home ovulation predictor kit can help you track fertilization.

If this method is used, it’s best to take a pregnancy test “approximately 14 days after a documented ovulation,” says Zaher Merhi, M.D., an OB-GYN, reproductive endocrinologist and founder of Rejuvenating Fertility Center with locations in New York and Connecticut.

Signs You Should Take A Pregnancy Test

The biggest indicator it’s time to take a pregnancy test is a missed period. It isn’t the only sign, however. Symptoms that signal it may be time to take a pregnancy test, according to Dr. Merhi, include:

• Missing a period
• Breast fullness/soreness
• Frequent urination
• Nausea
• Vomiting
• Fatigue
• Abdominal bloating

When Is the Best Time to Take a Pregnancy Test?

You can take a pregnancy test any time of the day. But if there’s a chance you’re early in pregnancy, take it in the morning when your urine is most concentrated so the test can more easily detect the HCG hormone, says Dr. Culwell.

“The best time in the cycle to take a test would be after you have missed a period,” says Dr. Culwell. “This will make it less likely that you might miss an early pregnancy if the HCG levels are too low to be picked up by the test.”

Where To Buy A Pregnancy Test

You can buy a pregnancy test at most drug stores and grocery stores, or even online.

How Soon Can You Take a Pregnancy Test?

At-home pregnancy tests are regulated by the Food and Drug Administration (FDA), meaning their accuracy and labeling is evaluated before they reach store shelves. When it comes to the accuracy of at-home pregnancy tests, research shows if the test is used as directed, an inaccurate result is rare. While false-positive pregnancy test results are uncommon, if you do receive an inaccurate result, it’s more likely to be a false-negative. In this case, it’s likely you’re testing too early, before HCG can be detected.

“For most women who have a regular menstrual cycle, a pregnancy test could be taken on the expected day of the period,” says Dr. Merhi. “The earliest [time to test] would be the expected day of the period; however, I usually tell patients to wait at least a few days (or one week) after the expected day of the period in order to lower the chances of having a false result.”

It’s worth noting that at-home pregnancy tests accuracy claims—many of which advertise an accuracy rate of 99% from the day of the expected period—are based on data used in a sterile laboratory testing environment. If you think you received an inaccurate result, you can either wait and test again a few days later or see your doctor for a blood test, which can detect HCG earlier than at-home tests and has an accuracy rate of 99%.