Author name: hpvsolutions.com

Stage 3: HSIL / CIN3

A Closer Look at Severe Dysplasia and Treatment Paths

It’s crucial for individuals diagnosed with CIN 3 to work closely with their healthcare provider to determine the most appropriate treatment plan based on their specific circumstances and health history.

Neoplasia System

CIN1 – Cervical intraepithelial neoplasia Grade 3

Bestheda System

HSIL – High-grade squamous intraepithelial lesion

Severe cervical dysplasia CIN3 / HSIL

Cervical intraepithelial neoplasia grade 3 (CIN 3) is considered a high-grade cervical dysplasia, representing severe abnormalities in the cervical cells. CIN 3 is also referred to as carcinoma in situ, indicating that the abnormal cells are present and confined to the surface layer of the cervix.

Can cervical dysplasia be cured?

Yes. Removing or destroying the abnormal cells cures cervical dysplasia in about 90% of all cases. Cervical dysplasia rarely progresses to cancer. When it does progress, it does so very slowly, allowing time for your healthcare provider to intervene.

Treatments Stage 3

Cold knife conization

This surgical procedure removes the abnormal areas removing a cone-shaped piece of the cervix. The cone-shaped piece of tissue contains the abnormal cells. It was once the preferred method of treating cervical dysplasia, but now it’s reserved for more severe cases. Conization can provide a sample of tissue for further testing. It has a somewhat higher risk of complications, including cervical stenosis and postoperative bleeding.

CKC is performed with a scalpel, typically under general or regional anesthesia, and is conventionally believed to yield a larger specimen with less thermal damage to the margins compared to other excisional methods.

Source: Obgyn

Surgical uterus removal

Hysterectomy involves removing your uterus. A hysterectomy may be an option in cases where cervical dysplasia persists or doesn’t improve after other procedures.

Fertility & Pregnacy Considerations

Treatment for CIN 3 may impact fertility, especially if a large portion of the cervix is removed. It’s important for individuals to discuss fertility concerns with their healthcare provider before undergoing treatment.

If the woman is pregnant, it is advisable to wait till the baby is born. If the condition is severe and the woman is not going to have children, removing the uterus is the course of action taken.

Stage 2: HSIL / CIN2

Regression or Intervention

While some CIN 2 lesions may regress on their own, they have a higher likelihood of persisting or progressing to CIN 3.

Neoplasia System

CIN2 – Cervical intraepithelial neoplasia Grade 2

Bestheda System

HSIL – High-grade squamous intraepithelial lesion

Moderate cervical dysplasia CIN2 / HSIL

CIN 1 cervical dysplasia rarely becomes cancer and often goes away on its own. CIN 2 and 3 are more likely to require treatment to prevent cancer. Cervical intraepithelial neoplasia grade 2 (CIN 2) represents a more advanced stage of dysplasia, indicating moderate abnormalities in the cervical cells.

How long does it take for CIN1 to become CIN2?

CIN is graded as 1, 2, or 3 depending on the how much of the epithelial layer contains atypical cells. CIN1, or mild dysplasia, often spontaneously regresses, usually within 6 to 12 months. When cellular atypia involves two-thirds of the thickness of the epithelium, it is designated as CIN2.

Can HPV CIN2 go away?

There was evidence that approximately 40% of undiagnosed CIN-2 will regress over 2 years but CIN-2 caused by HPV16 may be less likely to regress than CIN-2 caused by other high-risk HPV genotypes

Treatments Stage 2

Loop electrosurgical excision procedure (LEEP)

The Loop Electrosurgical Excision Procedure (LEEP) is one of the most commonly used approaches to treat high grade cervical dysplasia (CIN II/III, HGSIL) discovered on colposcopic examination. In the UK it is known as Large Loop Excision of the Transformation Zone (LLETZ).

This uses a thin looped wire charged with an electric current to remove a thin layer of a section of the cervix . The goal is to remove all the abnormal cells, including most or all of the cells with HPV.

Process

When performing a LEEP, the physician uses a wire loop through which an electric current is passed at variable power settings. Various shapes and sizes of loop can be used depending on the size and orientation of the lesion. The cervical transformation zone and lesion are excised to an adequate depth, which in most cases is at least 8 mm, and extending 4 to 5 mm beyond the lesion. A second pass with a more narrow loop can also be done to obtain an endocervical specimen for further histologic evaluation.

How painful is LEEP?

During the procedure, you may feel a little discomfort or cramping. Because numbing medicines are used, though, a lot of people don’t feel anything. After LEEP, you may have mild cramping for a day or so. Over-the-counter pain medicine can help.

The procedure has many advantages including low cost, high success rate, and ease of use. The procedure can be done in an office setting and usually only requires a local anesthetic, though sometimes IV sedation or a general anesthetic is used.

Source: Obgyn

About 1% to 2% of people may experience complications following the procedure, such as delayed bleeding or narrowing of their cervix (stenosis).

How do I know my cervix is healed after LEEP?

Don’t place anything inside your vagina (such as tampons or douches) or have vaginal intercourse for at least 4 weeks after your procedure. It usually takes about this long for your cervix to heal. During your follow-up appointment, your doctor will examine you and see if your cervix has healed.

What is the next step after a LEEP procedure?

The most common next step after a LEEP procedure is to get a pap smear in six months.

What is the success rate of LEEP procedure for CIN 2?

The success rate for LEEP is excellent, with a 90% cure rate. A LEEP’s success depends on various actors, including how advanced your cervical dysplasia is and how much tissue must be removed. In those instances where abnormal cells grow back, your provider may recommend an additional LEEP or other treatments.

Does cervix grow back after LEEP?

Does the cervix grow back after a LEEP procedure? Yes. During the four- to six-week recovery time, new healthy tissue grows on your cervix to replace the removed abnormal tissue.

Positive margin after LEEP

A positive margin after LEEP (defined as a histopathological finding of CIN along the specimen margin regardless of the CIN grade) is a well-defined predictor of persistent/recurrent disease.

Some investigations have suggested that secondary conization (including cold knife conization and LEEP) or hysterectomy should be applied in patients who have positive margins, while other studies have demonstrated that this population can be followed-up without the need for secondary surgery.

As the spontaneous regression rate of HSIL is much lower than that of LSIL it is reasonable to assume that patients with HSIL margins are more likely to have persistence/recurrence than patients with LSIL margins; therefore, a “wait-and-see” strategy would carry a high risk for persistence/recurrence in patients with HSIL margins in the initial cervical cone specimen. In contrast, if this hypothesis cannot be validated, secondary surgery for these patients may result in overtreatment to a certain extent.

A previous study demonstrated that HSIL can regress, which definitely challenged this hypothesis. However, as data on the persistence/recurrence rate in patients with HSIL, LSIL margins or HSIL margins are not available, the optimal treatment for patients with HSIL with positive margins remains controversial.

Therefore, it should be analyzed the data of patients with HSIL and HSIL margins to distinguish the factors that influence persistent/recurrent disease.

Is LEEP better than laser?

While it is unclear if one technique is superior to another, LEEP has largely replaced laser because laser is expensive, technically difficult, and can cause harm to medical personnel. Laser is still occasionally utilized.

Laser therapy

This uses light to burn away abnormal cells. This treatment is less common. Laser therapy is sometimes called laser ablation. This just means the laser burns away the abnormal cells. You have this treatment as an outpatient.

A laser beam is a very strong, hot beam of light. It burns away the abnormal area. You may notice a slight burning smell during the treatment. This is nothing to worry about. It is just the laser working. You can go home as soon as this treatment is over.

Freezing (cryosurgery) Cryotherapy

This involves freezing the abnormal cells with liquid nitrogen or carbon dioxide.

What is the success rate of cryotherapy for HPV?

Cryotherapy may be performed after abnormal cells are found during a Pap test, colposcopy, or biopsy. In most cases (about 85-90% of the time), cryotherapy cures abnormal cells so that the problem does not come back.

Pregnacy

If the woman wants to get pregnant, they may wait for one year before the procedure

At a glance

FAQ: HPV at a Glance

Human Papillomavirus (HPV) is a common group of viruses with diverse strains, each carrying its own implications. Here’s a brief overview:

HPV is responsible for:

  • almost all cases of genital warts and cervical cancer
  • 90% of anal cancers
  • 78% of vaginal cancers
  • 25% of vulvar cancers
  • 50% of penile cancers
  • 60% of oropharyngeal cancers

How HPV is spread

You do not need to have penetrative sex.

You can get HPV from:

  • any skin-to-skin contact of the genital area
  • vaginal, anal or oral sex
  • sharing sex toys

Symptoms of HPV


HPV does not usually cause any symptoms.

Most people who have it do not realise and do not have any problems.

Screening tests are used to check for a disease or condition when there are no symptoms. The goal of screening is to find health problems early, when they may be easier to treat.

Understanding HPV involves acknowledging its dual nature—manifesting as both harmless warts and potentially life-threatening cancers. Vigilance through vaccination, safe practices, and regular screenings remains our most potent defense against the multifaceted impact of HPV.

+ Info Genital

Understanding Genital Warts

Human Papillomavirus (HPV) is a group of related viruses that can infect the genital area and other mucous membranes, such as the mouth and throat. HPV is the most common sexually transmitted infection (STI) worldwide. Some strains of HPV can lead to genital warts, which are a common symptom of HPV infection.

Genital warts are a symptom of HPV infection caused by certain strains of the virus, most commonly HPV types 6 and 11. These warts can appear on the genitals, in the pubic area, on the inner thighs, or around the anus. They can vary in size and appearance, from small, flesh-colored bumps to larger clusters that resemble cauliflower.

While the infection is similar in men and women, there are some differences in how genital warts manifest and progress:

Women

Commonly appear on the vulva, in or around the vagina, cervix, and anus.

May develop internal genital warts on the cervix, which may not be visible and can only be detected through a Pap smear or other diagnostic methods.

May experience bleeding between periods or after intercourse, especially if warts are present on the cervix.

Certain strains of HPV that cause genital warts can also increase the risk of cervical cancer.

Men

Are often found on the penis, scrotum, and around the anus.

Do not have internal genital warts in the same way, as their internal genital structures are different.

May notice small, flesh-colored bumps on the genital or anal areas.

Are at a lower risk of developing complications, they can still experience discomfort and psychological stress.

Source: Wikipedia

FAQ on Genital Warts

What do early signs of genital warts look like?

Genital warts look like skin-colored or whitish bumps that show up on your vulva, vagina, cervix, penis, scrotum, or anus. They kind of look like little pieces of cauliflower. You can have just one wart or a bunch of them, and they can be big or small. They might be itchy, but most of the time they don’t hurt.

What can be mistaken for genital warts?

Molluscum contagiosum can be mistaken for genital warts or pimples. If you notice any unusual skin lesions, see your doctor or health professional for an accurate diagnosis. There is no test for molluscum contagiosum. It is diagnosed through a physical examination by looking at the appearance of the lesions.

How long could I have had genital warts without knowing?

Keep in mind that genital warts may not appear for months to years after having sexual contact with an infected person.

How long do genital warts last?

Most HPV infections that cause genital warts will go away on their own, taking anywhere from a few months to two years. But even if your genital warts disappear without treatment, you may still have the virus. When left untreated, genital warts can grow very large and in big clusters.

Can I spread genital warts by touching myself?

A different strain of HPV causes the type of warts you find on other parts of your body. You can’t get genital warts by touching yourself or someone else with a wart on your hands or feet. Genital warts spread through: Intercourse, including anal, vaginal-penile and vaginal-vaginal.

Will genital warts grow back if you cut them off?

After treatment, warts may continue to grow if the therapy proved ineffective or didn’t entirely remove the wart. Additionally, if treatment required an incision to be made in the skin, that incision can become re-infected with HPV – meaning a new wart can grow.

What makes genital warts worse?

If you already have genital warts, shaving and waxing your pubic hair can lead to more widespread infection. That’s because these hair removal techniques can cause tiny cuts and abrasions or irritation of the skin, which can allow the virus to enter and infect a larger area of skin.

Treatment to beat them

Topical OTC creams

Topical Creams: Provider administration

There is no cure for HPV itself, but genital warts can be treated and removed. The choice of treatment depends on the size and location of the warts. Treatment options include

GENITAL WARTS
Podophyllin resinA brownish and yellowish chemical that is applied directly to the affected area and allowed to air-dry. This chemical will damage the warts.May cause a burning sensation as it dries. The solution can be absorbed into the body and can cause side effects. Thus, some providers may thoroughly wash off the solution 1-4 hours after application.
Podophyllin (Podocon-25) and podofilox (Condylox). Podophyllin is a plant-based substance that destroys genital wart tissue. A health care professional puts this solution on your skin. Podofilox contains the same active compound, but you can put it on at home.Never place podofilox inside your body. Also, this medicine isn’t recommended for use during pregnancy. Side effects can include mild skin irritation, sores and pain.
Imiquimod (Zyclara)This cream seems to boost the immune system’s ability to fight genital warts. Do not have sexual contact while the cream is on your skin. It might weaken condoms and diaphragms and irritate your partner’s skin.One possible side effect is a change in skin color where the medicine is used. Other side effects might include blisters, body aches or pain, a cough, rashes, and fatigue.
Trichloroacetic (TAC) or Bichloracetic acid (BCA)Chemicals that destroy the warts by burning them. A small amount is applied only to the warts and allowed to dry. The warts will turn a white color, shrink and then disappear. Can be repeated weekly and may require multiple treatments.Chemicals that destroy the warts by burning them. A small amount is applied only to the warts and allowed to dry. The warts will turn a white color, shrink and then disappear. Can be repeated weekly and may require multiple treatments.
Interlesional interferonApplied as cream or injection. Interferon triggers your immune system to fight infection. Interferon may be applied directly to genital warts as a cream or injected into the warts and the skin surrounding them. May require multiple treatments.Usually used if other treatment methods have failed.
GENITAL AND ANAL WARTS
Sinecatechins (Veregen)This ointment can treat genital warts on the body and warts in or around the anus.Side effects can include a change in skin color, itching or burning, and pain.

Electrocautery

Electrocautery removes genital warts on the penis, vulva, or around the anus by burning them with a low-voltage electrified probe. Electrocautery is usually done in a doctor’s office or a clinic. The injection of a numbing medicine (local anesthetic) is usually used for pain control.

Surgical removal

The doctor uses a local anesthetic to numb the skin or the cervix and then excises the wart or abnormal tissue using a scalpel. Stitches are typically necessary, which dissolve on their own in two to three weeks. Sexual activity should be avoided during the healing process, which can take about two to four weeks.

Laser therapy

A laser can be used to destroy genital warts. Laser surgery may be done in a doctor’s office or clinic, a hospital, or an outpatient surgery centre. Local or general anesthetic may be used. Which one you get depends on how many warts need treatment and the size of the area to be treated.

Cryotherapy: freezing the warts

Cryotherapy (cryosurgery) destroys genital warts by freezing them. A doctor applies a very cold substance, such as liquid nitrogen, around the warts to freeze them. You may have a mild or moderate burning sensation during treatment.

CO2 Laser therapy vs cryotherapy in treatment of genital warts

Generally, the efficacy of CO2 laser treatment of external genital warts was approximately two fold greater than cryotherapy and it was associated with lower recurrence rate.

Pregnancy

Genital warts are not dangerous for pregnant women. They may cause discomfort, itching and pain, but they are not dangerous. Existing warts may grow faster or bigger during pregnancy due to changes in your hormones or immune systems. This may make things like urinating uncomfortable.

The treatment of genital warts in infants includes removing them under general anesthesia or applying a topical medication (podophyllin). However, many babies who contract HPV during delivery never become symptomatic because their immune system is strong enough to fight the infection. 

Genital wart removal is recommended during pregnancy. Specific types of HPV (6 and 11) can be transmitted to infants and children causing respiratory problems.

Please note that Podofilox, Imiquimod, and Podophyllin are not recommended for use during pregnancy as they are absorbed by the skin and may cause birth defects in the baby.

Things to keep in mind after surgical procedures:

  • You may have a slightly odorous watery and/or bloody discharge for several weeks after procedure. You can wash the labia (vaginal lips) with warm water several times throughout the day and use sanitary pads not tampons.
  • Avoid intercourse or douching for at least 3 weeks following the procedure. (Note: douching is generally not recommended, ever, as it can worsen — and may cause — GYN conditions.)
  • Can use Tylenol or Advil as needed for pain relief.

Other names for GW

While these terms may be used in a medical context, “genital warts” is the most commonly recognized and straightforward way to refer to this condition.

Condyloma acuminatum:

  • “Condyloma” refers to a genital wart.
  • “Acuminatum” means pointed or acuminate, describing the appearance of the wart.

Venereal warts:

  • “Venereal” relates to sexual intercourse or sexually transmitted infections.
  • This term emphasizes the connection between the warts and sexual activity.

Anogenital warts:

  • “Ano-” refers to the anus, and “genital” refers to the reproductive organs.
  • This term is used to describe warts located in the genital and anal areas.

HPV-related lesions:

  • This term is more general and includes any abnormal tissue changes caused by the human papillomavirus, which can include genital warts.

Genital warts and vulvar neoplasia

Genital warts and vulvar neoplasia are two distinct conditions that affect the genital area in females. Here are the key differences between them:

Genital Warts

Genital warts are caused by certain strains of the human papillomavirus (HPV). They manifest as small growths or lumps on the genital and anal areas. Genital warts are generally considered benign (non-cancerous) and are categorized as a sexually transmitted infection (STI).

Caused by specific strains of HPV, primarily types 6 and 11.

Present as small, flesh-colored growths or lumps on the genital or anal area. They may be raised or flat and can vary in size.

Characterized by the presence of wart-like growths caused by HPV infection. Biopsy may reveal characteristic changes.

Generally considered benign and not associated with an increased risk of cancer. However, the same types of HPV that cause genital warts (such as types 6 and 11) can also cause other HPV-related cancers, like cervical cancer.

Vulvar Neoplasia

Vulvar neoplasia refers to abnormal cell growth in the vulvar tissues, which can be either benign or malignant. Malignant vulvar neoplasia can lead to vulvar cancer. It is not directly caused by HPV infection, but persistent HPV infection is a known risk factor for developing vulvar cancer.

The exact cause is not always clear, but it is often associated with chronic inflammation, older age, smoking, and long-term HPV infection.

Symptoms may include itching, pain, tenderness, or changes in the color or thickness of the skin on the vulva. In more advanced stages, a visible mass or ulceration may be present.

Involves abnormal cell growth in the vulvar tissues, which can be either non-cancerous (benign) or cancerous (malignant). Malignant cases are associated with cancerous changes in the cells.

May lead to vulvar cancer, especially in cases of malignant neoplasia. Persistent infection with high-risk HPV types is a known risk factor for vulvar cancer.

It’s important to note that both conditions require medical attention. Genital warts can be treated and managed, and regular screenings are essential to detect and manage vulvar neoplasia early, improving outcomes. Individuals with concerns about their genital health should consult with a healthcare professional for proper evaluation and guidance.

What can be mistakes with genital warts?

Several conditions can be mistaken for genital warts due to their similar appearance. Here are some possibilities:

Molluscum Contagiosum: Molluscum contagiosum is a viral skin infection that causes small, raised bumps on the skin. These bumps can resemble genital warts, but they tend to have a central dimple or indentation. Unlike genital warts, molluscum contagiosum lesions are often painless and may resolve on their own over time.

Skin Tags: Skin tags are small, soft growths that can develop in areas where the skin rubs against itself, such as the groin or genital area. While they may appear similar to genital warts at first glance, skin tags typically have a smoother surface and a narrower base than genital warts.

Sebaceous Prominence: Sebaceous prominence, also known as Fordyce spots, is a condition characterized by the appearance of small, raised bumps on the skin. These bumps are caused by enlarged oil glands and are usually painless. While they can occur in the genital area, they are not sexually transmitted and are not contagious.

Pearly Penile Papules (PPP): Pearly penile papules are small, dome-shaped bumps that commonly appear around the head of the penis. While they can resemble genital warts, PPP are harmless and not caused by a sexually transmitted infection. They are considered a normal variant of penile anatomy.

Folliculitis: Folliculitis is the inflammation or infection of hair follicles, often caused by bacteria, fungi, or ingrown hairs. It can cause red, inflamed bumps that may be mistaken for genital warts, especially if they occur in the pubic area. However, folliculitis typically resolves with proper hygiene and treatment.

If you notice any unusual bumps, lesions, or changes in the genital area, it’s important to consult a healthcare provider for an accurate diagnosis. A healthcare professional, such as a dermatologist or a doctor specializing in sexual health, can provide appropriate evaluation and recommend the necessary treatment, if needed. Additionally, practicing safe sex and getting regular STI screenings are essential for maintaining sexual health.

Virus Strains

Understanding HPV Strains: Types & Risks

Over 170 types of HPV have been identified, and they are designated by numbers. The most common types of HPV worldwide are 16 (3.2%), 18 (1.4%), 52 (0.9%), 31 (0.8%), and 58 (0.7%).
They may be divided into “low-risk” and “high-risk” types.  Low-risk types cause warts and high-risk types can cause lesions or cancer.

High Risk & Low Risk

  • High-risk HPV types can infect cervical cells and cause cervical cancer. They can also infect certain other cells to cause anal cancer, penile cancer, vaginal cancer, vulvar cancer, and oropharyngeal cancer (cancer in the middle of the throat, including the tonsils and the back of the tongue).Cervical cancer is almost always caused by high-risk HPV. Types 16 and 18 two strains account for 70% of cases.
  • Low-risk HPV types can cause genital warts. These are warts on the external and internal sex organs and glands. Genital warts do not turn into cancer.Types 6 and 11 are common causes of genital warts and laryngeal papillomatosis
WARTSTYPES
Common warts2, 7, 22
Plantar warts1, 2, 4, 63
Flat warts3, 10, 28
Anogenital warts6, 11, 42, 44 and others
DESEASETYPES
Anal dysplasia (lesions)16, 18, 31, 53, 58
Genital cancers
-Highest risk16, 18, 31, 45
-Other high-risk33, 35, 39, 51, 52, 56, 58, 59
-Probably high-risk26, 53, 66, 68, 73, 82
Epidermodysplasia verruciformismore than 15 types
Focal epithelial hyperplasia (mouth)13, 32
Mouth papillomas6, 7, 11, 16, 32
Oropharyngeal cancer16
Verrucous cyst60
Laryngeal papillomatosis6, 11

HPV Genotyping: Identifying Specific Strains

Genotyping is a laboratory technique used to identify and distinguish between specific types or strains of the human papillomavirus (HPV).
Purpose of Genotyping: While a standard HPV test detects the presence of the virus, genotyping goes a step further by identifying the exact type of HPV.
Different HPV types have varying levels of risk for developing into cancer.

Low-Risk Strains and Genital Warts:

  • Genotyping can also identify low-risk strains responsible for conditions such as genital warts.
  • Differentiating between high and low-risk strains helps guide healthcare decisions and interventions.

Identifying High-Risk Strains:

  • Highlight that genotyping can identify high-risk HPV strains, which are more strongly associated with the development of cervical and other cancers.
  • Common high-risk strains include HPV 16 and 18.

HPV tests – Variation between tests

Various types of HPV tests are currently available, and they use different technologies. The tests are broadly classified as those that detect the presence of DNA of high-risk HPV coding for L1 viral surface protein (HPV DNA tests) and those that detect the presence of messenger RNA (mRNA) coding for E6/E7 proteins of high-risk HPV types (HPV RNA tests).

Most of the currently available tests can detect the presence of any of the 12 high-risk HPV types. Some of the tests detect the presence of any of these HPV types in the sample without individually identifying the genotypes. Others may individually detect a limited number of genotypes (mostly HPV16 and HPV18) concurrently, with aggregate detection of the other high-risk HPV genotypes. The information on HPV16 and HPV18 received as part of the HPV test report (concurrent genotyping) is used for triage along with VIA, cytology, or colposcopy.

Source: WHO

Several techniques are employed for HPV genotyping to identify specific strains of the virus. The choice of technique may depend on factors such as sensitivity, specificity, cost, and the number of HPV types being targeted. Here are some commonly used techniques for HPV genotyping:

Polymerase Chain Reaction (PCR):

  • Principle: PCR is a molecular biology technique that amplifies DNA segments, allowing for the detection and identification of specific DNA sequences.
  • Application: HPV DNA is amplified using specific primers for targeted regions. The resulting DNA products are then analyzed to identify the HPV types present.

Reverse Line Blot Hybridization (RLB):

  • Principle: RLB is a technique that combines PCR amplification with DNA hybridization on a solid support (such as a membrane).
  • Application: After PCR amplification of HPV DNA, the products are hybridized to specific probes immobilized on a membrane. The pattern of hybridization indicates the presence of specific HPV types.

DNA Microarray:

  • Principle: DNA microarrays are solid supports containing a large number of unique DNA probes arranged in an array.
  • Application: HPV DNA is amplified through PCR and then hybridized to the microarray. The pattern of hybridization helps identify the specific HPV types present.

Line Probe Assays (LPA):

  • Principle: LPA is a molecular biology technique that combines PCR amplification with the detection of specific DNA sequences using labeled probes.
  • Application: PCR-amplified HPV DNA is hybridized to specific probes fixed on a strip or membrane. Detection of labeled DNA indicates the presence of specific HPV types.

Next-Generation Sequencing (NGS):

  • Principle: NGS allows for the high-throughput sequencing of DNA, providing detailed information about the entire genome.
  • Application: HPV DNA is sequenced, and the obtained sequence data are analyzed to identify specific HPV types. NGS can provide information on multiple HPV types simultaneously.

Pyrosequencing:

  • Principle: Pyrosequencing is a sequencing-by-synthesis method that detects the release of pyrophosphate during DNA synthesis.
  • Application: After PCR amplification of HPV DNA, pyrosequencing is used to determine the sequence. Specific sequence patterns identify the HPV types.

Single-Strand Conformation Polymorphism (SSCP):

  • Principle: SSCP is a technique that exploits the differences in mobility of single-stranded DNA fragments on a gel.
  • Application: PCR-amplified HPV DNA is denatured and separated on a gel. Variations in the single-stranded DNA mobility pattern help identify specific HPV types.

The choice of genotyping technique depends on factors such as the level of resolution needed, the number of HPV types to be identified, and the available resources. Each technique has its advantages and limitations, and researchers or clinicians may choose the most suitable method based on the specific requirements of their study or clinical setting.

Prevalence of Each Type

The prevalence of the types of Human Papillomavirus (HPV) is significant throughout the world, being one of the most common sexually transmitted viruses. It is estimated that the vast majority of sexually active people will contract at least one form of HPV at some point in their lives.

HPV types vary in their oncogenic potential, and high-risk types, such as types 16 and 18, are linked to an increased risk of developing cervical and other related cancers.

Classifications

What are CIN1 and LSIL?

There are many systems in use for classifying precancerous conditions of the cervix. These two are world-wide used.

The Bestheda System (since 1990)

This classification is recommended by WHO for cytological reports. It was developed in 1990 in the United States National Cancer Institute. It is a system for reporting cervical or vaginal cytologic diagnoses, used for reporting Pap semar results.

  • LSIL (also called low-grade squamous intraepithelial lesion, or mild dysplasia) seen on a Pap test is generally CIN 1.
  • HSIL (also called high-grade squamous intraepithelial lesion, or moderate or severe dysplasia) seen on a Pap test can be CIN 2, CIN2/3, or CIN 3.
  • ASCUS and ASCH classify Atypical cells

The name comes from the location (Bestheda, Maryland) of the conference sponsored by the National Institutes of Health, that stablisehed the system.

The Cervical Intraepithelial Neoplasia (since 1968)

CIN is the term used to describe abnormal cervical cells that were found on the surface of the cervix after a biopsy.

  • CIN 1 changes are mild, or low grade. They usually go away on their own and do not require treatment.
  • CIN 2 changes are moderate and are typically treated by removing the abnormal cells.

However, CIN 2 can sometimes go away on its own. Some women, after consulting with their health care provider, may decide to have a colposcopy with a biopsy every 6 months.
CIN 2 must be treated if it progresses to CIN 3 or does not go away in 1 to 2 years.

  • CIN 3 changes are severely abnormal. Although CIN 3 is not cancer, it may become cancer and spread to nearby normal tissue if not treated. Unless you are pregnant, it should be treated right away.

Comparaison

NLM: Negative for intrapetithelial lesion or malignacy
LISL: Low grade squamous intrapithelial lesion
HSIL: Low grade squamous intrapithelial lesion
ASC-US: atypical squamous cells of undetermined significance
ASC-H: atypical squamous cells suspicious for HSIL
CIN: cervical intraepithelial neoplasia

Smear Appearance

Papanicolaou (PAP) cytological classifications

The Papanicolaou (PAP) cytological classifications are used to interpret Pap smear results, categorizing cervical cells and assessing the presence of potential abnormalities. Here’s the interpretation of the mentioned categories:

PAP II-p (Papanicolaou II-partial):

  • Indicates normal cells but with some non-specific changes that may be caused by infections or other benign factors. It is generally not considered a worrisome result.

PAP III-p (Papanicolaou III-partial):

  • Indicates more noticeable cellular changes but is still not a definitive result of precancerous lesion. It may suggest the presence of abnormal cells, requiring closer follow-up or additional tests.

PAP IIID1 (Papanicolaou IIID1):

  • This classification is often associated with the Bethesda system as “Atypical squamous cells of undetermined significance” (ASC-US). It indicates more pronounced cellular changes than PAP III but is not clear enough to confirm the presence of a precancerous lesion.

PAP IIID2 (Munich III) (Papanicolaou IIID2):

  • Similar to PAP IIID1 but with a higher suspicion of precancerous lesions. The “Munich III” classification is often associated with high-grade cells and may require more intensive follow-up or biopsy for a more accurate assessment.

It’s important to note that these classifications may vary slightly depending on the system used in different countries or medical institutions. Additionally, the interpretation and management of these results should be done by healthcare professionals, such as gynecologists or pathologists, who will consider the clinical context and other factors to determine the appropriate course of action.

Screening & Detection

Screening & Detection Insights

Welcome to a comprehensive exploration of HPV testing, its implications, and potential outcomes. Human Papillomavirus (HPV) is a prevalent infection with significant health ramifications, making screening a critical aspect of preventive healthcare.

Based on your individual risk of developing severe cervical cell changes that could become cervical cancer, you may be advised to

  • return for a repeat HPV test or HPV/Pap cotest in 1 or 3 years
  • have a colposcopy and biopsy
  • receive treatment

There are various screening techniques available, highlighting their effectiveness and importance in identifying HPV infections and related abnormalities. Understanding the screening process is key to maintaining optimal health and preventing the progression of potential complications.

HPV TEST / PAP SMEAR

The test is similar but they search for a different outcome:

The HPV test looks for the virus (human papillomavirus) that can cause these types of cellular changes in the cervix.

The Pap test (or Pap smear) looks for precancers, which are changes in the cells of the cervix that could become cancer if not treated properly.

Source: WHO

HPV/Pap cotest: uses combine both to check for both high risk HPV and cervical cell changes. If your doctor finds that you have a type of HPV that can lead to cancer, they may suggest you get Pap tests more often to watch for signs of abnormal cell changes in the genital area.

HPV test results

HPV test results show whether high-risk HPV types were found in cervical cells. An HPV test will come back as a negative test result or a positive test result.

  • Negative HPV test result: 

High-risk HPV was not found. You should have the next test in 5 years. You may need to come back sooner if you had abnormal results in the past.

  • Positive HPV test result: 

High-risk HPV was found. Your healthcare provider will recommend  follow-up steps you need to take, based on your specific test result.

ResultWhat it means
HPV found (HPV positive), but no abnormal cell changesYou’ll be invited for screening in 1 year and again 1 year later if you still have HPV. If you still have HPV after 2 years, you’ll be asked to have a colposcopy.
HPV found (HPV positive) and abnormal cell changesYou’ll be asked to have a colposcopy.

What does it mean if you have a positive HPV test after years of negative tests?

Sometimes, after several negative HPV tests, a woman may have a positive HPV test result. This is not necessarily a sign of a new HPV infection. Sometimes an HPV infection can become active again after many years.

Pap test results

Pap test results show whether cervical cells are normal or abnormal. A Pap test may also come back as unsatisfactory.

Normal or negative Pap test results: No abnormal cervical cells were found.

Abnormal or positive Pap test results:  Some of the cells of the cervix look different from the normal cells. Abnormal Pap test results include

  • Atypical squamous cells of undetermined significance (ASC-US):  It means that some cells don’t look completely normal, but it’s not clear if the changes are caused by HPV infection.
  • Atypical glandular cells (AGC): Some glandular cells were found that do not look normal.
  • Low-grade squamous intraepithelial lesions (LSIL): There are low-grade changes that are usually caused by an HPV infection.
  • Atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H): Some abnormal squamous cells were found that may be a high-grade squamous intraepithelial lesion (HSIL), although it’s not certain.
  • High-grade squamous intraepithelial lesions (HSIL): There are moderately or severely abnormal cervical cells that could become cancer in the future if not treated.
  • Adenocarcinoma in situ (AIS): An advanced lesion (area of abnormal growth) was found in the glandular tissue of the cervix. AIS lesions may be referred to as precancer and may become cancer (cervical adenocarcinoma) if not treated.
  • Cervical cancer cells (squamous cell carcinoma or adenocarcinoma): Cancer cells were found; this finding is very rare for people who have been screened at regular intervals.  

Follow-up tests

Keep in mind that most people with abnormal cervical screening test results do not have cancer. However, if you have an abnormal test result, it’s important to get the follow-up care that your health care provider recommends.

State of dormacy

Human Papillomavirus (HPV) can sometimes enter a state of dormancy in the human body. When HPV is in a dormant state, it means that the virus is present but not actively causing any symptoms or abnormalities. The virus can exist in a latent or inactive form, and during this period, it may not be detectable through routine tests. Key points about HPV dormancy include:

Asymptomatic Carrier State:

  • Many people who contract HPV may never experience any symptoms, and the virus can remain dormant in their bodies.
  • An individual may be an asymptomatic carrier, meaning they carry the virus but do not develop visible warts or other HPV-related conditions.

Reactivation:

  • HPV can be reactivated, leading to the recurrence of symptoms or the development of new ones.
  • Factors such as a weakened immune system, stress, or other health conditions may contribute to the reactivation of the virus.

Persistent Infections:

  • In some cases, HPV infections persist over an extended period without causing noticeable symptoms or complications.
  • Persistent infections with high-risk HPV types are associated with an increased risk of developing cervical and other cancers.

Screening and Detection:

  • Dormant HPV infections may not be easily detectable through routine screening methods.
  • Screening methods, such as Pap smears and HPV DNA tests, are designed to identify active infections or cellular changes that may indicate a risk of developing cervical cancer.

Is citology and pap smear the same?

Yes, in the context of HPV (Human Papillomavirus) and cervical cancer screening, “cytology” and “Pap smear” are often used interchangeably, though there are subtle differences.

Cytology:

  • Cytology refers to the study of cells. In the context of cervical cancer screening, cytology involves examining cells collected from the cervix to detect any abnormalities.
  • Cytology is a broader term that encompasses various methods of studying cells, and it can be used for different types of cytological examinations, not limited to cervical cells.

Pap Smear:

  • A Pap smear, or Papanicolaou smear, is a specific type of cytological examination used for cervical cancer screening.
  • During a Pap smear, cells are collected from the cervix and then examined under a microscope to identify any abnormal changes in the cervical cells that could be indicative of HPV infection or precancerous conditions.

COLPOSCOPY

During this procedure, a lighted instrument called a colposcope magnifies the cervix, bringing abnormal cells into view. Then they are removed to test them in a lab for signs of precancer or cancer (biopsy).

Biopsy findings

Biopsy samples are checked by a pathologist for CIN.CIN is the term used to describe abnormal cervical cells that were found on the surface of the cervix after a biopsy.

CIN is graded on a scale of 1 to 3, based on how abnormal the cells look under a microscope and how much of the cervical tissue is affected. LSIL changes seen on a Pap test are generally CIN 1. HSIL changes seen on a Pap test can be CIN 2, CIN2/3, or CIN 3.

  • CIN 1 changes are mild, or low grade. They usually go away on their own and do not require treatment.
  • CIN 2 changes are moderate and are typically treated by removing the abnormal cells. However, CIN 2 can sometimes go away on its own. CIN 2 must be treated if it progresses to CIN 3 or does not go away in 1 to 2 years.
  • CIN 3 changes are severely abnormal. Although CIN 3 is not cancer, it may become cancer and spread to nearby normal tissue if not treated.
Colposcopy view

Is VIA and colposcopy the same?

No, VIA (Visual Inspection with Acetic Acid) and colposcopy are not the same procedures, but they are related in the context of HPV (Human Papillomavirus) and cervical cancer screening.

VIA (Visual Inspection with Acetic Acid):

  • VIA is a simple and low-cost screening method for detecting cervical abnormalities, including those caused by HPV.
  • During VIA, a healthcare provider applies acetic acid (vinegar) to the cervix, and visual changes in the cervical tissue are observed.
  • The acetic acid causes abnormal cells to temporarily turn white, making them more visible.

Colposcopy:

  • Colposcopy is a more advanced and detailed examination compared to VIA.
  • It involves using a colposcope, which is a magnifying instrument, to closely examine the cervix and vaginal tissues.
  • Colposcopy is often performed if there are abnormal results from a Pap smear or other screening tests, including VIA.

Find more information about your results here

Most HPV infections (90%) clear up on their own within 2 years.
There is no treatment for the virus itself. However, there are treatments for the health problems that HPV can cause.

From negative results offering peace of mind to positive results prompting further investigation, each outcome plays a crucial role in managing and maintaining reproductive health.

By comprehending the lifecycle of HPV and its potential consequences, you can take proactive steps towards prevention and early management.

Implications for Women:

  • For women, a positive result may lead to additional screenings, such as colposcopy, to examine cervical cells more closely.
  • Abnormal cell changes can be monitored and treated to prevent the progression to cancer.

Implications for Men:

  • HPV can affect men as well, causing genital warts or, in some cases, leading to cancers such as penile or anal cancer.
  • Beaware of the importance of regular health check-ups for men.

No test for other cancers

There aren’t any approved tests for identifying HPV on the vulva, vagina, penis, scrotum, rectum or anus. HPV-related cancers on these body parts are much less common than cervical cancer. There’s no similar test for the strains of HPV that cause cancer in men, except for anal cancer.

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