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Vaccines

Vaccine Types: Vaccination Against Infection

HPV vaccines are highly effective in preventing infection with the most common types of the virus. Gardasil 9 and Cervarix are two widely used HPV vaccines that provide protection against multiple high-risk HPV strains. Vaccination is recommended for both males and females, ideally before the onset of sexual activity.

Gardasil 9

Gardasil 9, developed by Merck, it is an extension of the original Gardasil vaccine, offering immunity against nine high-risk HPV types:

  • HPV-16 & HPV-18. These are the two most common high-risk strains of HPV. These strains cause 70% of cervical cancers, 90% of anal cancers and many cancers that can affect your throat and genitals.
  • HPV-31, 33, 45, 52 & 58. Together, these strains cause an additional 20% of cervical cancers.
  • HPV-6 & HPV-11. These strains cause 90% of genital warts.

Gardasil protects against infections associated with:

  • HPV-16 & HPV-18
  • HPV-6 & HPV-11
  • Remains effective:

Gardasil (2006) 10+ years after vaccination.

Gardasil-9 (2014) at least 6 years after vaccination.

Vaccination is most effective when administered before exposure to the virus.

Not all HPV vaccines provide the same protection. There are three different vaccines. Each protects against different strains of HPV.

Cervarix

Cervarix, developed by GlaxoSmithKline, is another HPV vaccine designed to provide protection against specific high-risk HPV types, primarily targeting cervical cancer.

  • Targeted HPV-16 & HPV-18: Cervarix is designed to protect against HPV types 16 and 18, which are among the most common high-risk strains associated with cervical cancer.
  • Emphasis on Cervical Cancer Prevention: While also contributing to the prevention of other HPV-related cancers, Cervarix has a particular emphasis on reducing the incidence of cervical cancer in women.

  • Remains effective:

Cervarix (2009) 10+ years after vaccination.

Age Recommendations:

The Centers for Disease Control and Prevention (CDC) recommends routine vaccination for adolescents aged 11-12 years, with catch-up vaccinations for those up to age 26. The age limit for getting vaccinated (first 26 and now 45) is based on the thinking that most people have had sex (and potentially been exposed to multiple strains of HPV) by adulthood. If you’ve already been exposed, the vaccine won’t provide much benefit.

  • Children between ages 11 & 12. The HPV vaccine is part of the vaccination schedule for children between 11 and 12, but children as young as 9 years old can safely receive it. The goal is to vaccinate children before they become sexually active and risk exposure.
  • Adults up to and including age 26. The vaccine is also recommended for adults up to age 26. This includes people who started the series as a child, teen or young adult but didn’t finish it.
  • Some adults up to and including age 45: In 2018, the Federal Drug Administration (FDA) expanded the age range from 26 to 45. The recommendation was based on research that showed the vaccine prevented HPV infections among adults in this age range, too.

What is the HPV vaccination schedule?

You’ll get the vaccine as a series of shots. The number of shots depends on the age at the first dose.

  • From age 9 to 15: You’ll need two shots to be fully protected. You should get the second shot six to 12 months after getting the first shot. At this age, your immune system is especially strong. Vaccination at a young age provides the strongest immune response and the best protection against HPV infection.
  • Ages 15 and up: You’ll need three shots to be fully protected. You should get the second shot one to two months after your first shot. You should get the third shot six months after your first shot.

HPV Vaccine Side Effects

Vaccines against Human Papillomavirus (HPV), such as Gardasil, Gardasil 9, and Cervarix, are generally safe and effective in preventing infections by certain types of HPV. However, as with all vaccines, side effects can occur. Most of these effects are mild and temporary.

Common Side Effects:

Pain at the injection site: This is the most common side effect and may be accompanied by redness or swelling.

Fever: A mild fever may occur after vaccination.

Headache: Some individuals may experience headaches after the injection.

Fatigue: A feeling of tiredness or weakness.

Nausea: Some people may feel temporarily nauseous.

Muscle or joint pain: Pain in the muscles or joints.

Less Common Side Effects:

Dizziness or fainting: In rare cases, some people, especially adolescents, may faint after receiving the vaccine. It is recommended that individuals sit or lie down for about 15 minutes after vaccination to prevent fainting.

Swollen lymph nodes: This can occur in rare instances.

Allergic Reactions:
  • Severe allergic reactions (anaphylaxis): These are extremely rare but can occur. Symptoms include difficulty breathing, swelling of the face and throat, and a severe rash. These reactions typically happen shortly after vaccination, so healthcare professionals monitor individuals for a few minutes after the injection to manage any immediate reactions.
Important Considerations:
  • People with severe allergies: Those with severe allergies to any component of the vaccine should not receive it.
  • Pregnancy: It is not recommended to administer the vaccine to pregnant women, although studies have shown there is no significant risk. Women who are pregnant or think they might be should inform their doctor before receiving the vaccine.
Benefits of Vaccination:
  • HPV vaccines are highly effective in preventing infections by the HPV types that cause the majority of cervical cancers, anal cancers, and other HPV-related cancers, as well as genital warts.
  • Preventing HPV infections significantly reduces the incidence of these cancers and diseases.

Warts Medical Treatments

Medical & Surgical Treatments for Warts

The human papillomavirus (HPV) can cause genital warts and other types of warts. There are treatments available to remove or manage the warts associated with the infection.

Topical Treatments

Keratolytic Agents

Keratolytic agents are substances that help remove dead cells from the outer layer of the skin and are used in some cases to treat warts caused by the human papillomavirus (HPV).

The keratolytic action refers to the ability of a substance to dissolve or shed keratinized cells, which are cells rich in keratin, a fibrous protein found in the outer layer of the skin. Keratin is a key structural protein in the epidermis, nails, and hair.

When a keratolytic substance is applied to the skin, it works by breaking down or softening the keratin cells, thereby facilitating the removal of dead or abnormal cells. This action is beneficial in treating various skin conditions such as warts, calluses, corns, and other lesions where there is excessive thickening of the stratum corneum of the skin.

In the context of wart treatment, keratolytic agents like salicylic acid, lactic acid, and glycolic acid are used to soften and help shed the affected layers of skin that make up the warts. This can make it easier to remove the warts over time.

Salicylic Acid

Prescription-strength wart medications containing salicylic acid work by gradually removing layers of a wart.

Studies show that salicylic acid is most effective when combined with freezing

Trichloroacetic Acid (TCA)

This acid is applied directly to the wart and destroys the affected tissue. With this method, the doctor first shaves the surface of the wart and then applies the acid with a wooden applicator. Treatments need to be repeated approximately every week. Side effects include stinging and burning.

Glycolic and Lactic Acid

Both are alpha-hydroxy acids (AHA). They work by exfoliating the skin’s surface layer, promoting cell renewal, and softening skin texture.

They help to soften and exfoliate the affected skin.

Blistering Agent

A blistering agent generally refers to substances that can cause blisters or vesicles on the skin. Cantharidin, a chemical that generates a blister under the wart, is applied. You may need to return to the clinic in about a week to have the dead wart tissue removed with tweezers.

Cantharidin is a chemical obtained from the blister beetle Lytta vesicatoria, commonly known as the “Spanish fly.” Cantharidin has vesicant properties, meaning it can cause blister formation on the skin. Historically, it has been used in topical applications for the treatment of warts, especially common warts.

In the context of wart treatment, cantharidin is applied as a topical solution directly on the wart. The idea is that the substance causes a blister under the wart, and when the blister detaches, it removes the wart layers with it. However, cantharidin does not directly destroy the human papillomavirus (HPV), which is the underlying cause of warts.

It is important to note that the use of cantharidin for wart treatment is not as common today as it was in the past. There are other treatments that are safer and more effective, such as salicylic acid, cryotherapy, trichloroacetic acid (TCA), and other topical agents, which are usually preferred due to their proven safety and efficacy profiles.

Transmission

Transmission & Symptoms of HPV

Transmission

Transmission of High-Risk HPV That Causes Cancer

High-risk Human Papillomavirus (HPV) is known for its ability to cause various types of cancer. The most dangerous types of HPV in terms of cancer risk are types 16 and 18, although other types like 31, 33, 45, 52, and 58 are also associated with cancers. Below is an outline of the contagion of high-risk HPV and the types of cancer it can cause:

HPV is primarily transmitted through sexual contact. This includes:

  • Vaginal, anal, and oral sexual relations: Genital-genital, genital-anal, and genital-oral contact can transmit the virus.
  • Skin-to-skin contact: HPV can be transmitted even without penetration, through intimate skin contact in the genital area.
  • Contaminated objects: Although less common, the virus can be transmitted through the sharing of sex toys or contact with contaminated surfaces.

Transmission of Low-Risk HPV That Causes Warts

Human Papillomavirus (HPV) can cause different types of warts depending on the strain of the virus and the part of the body affected. The contagion of HPV and the appearance of warts vary according to the type of wart and its location.

Genital Warts:
  • Caused by: Mainly HPV types 6 and 11.
  • Transmission:
  • Sexual contact: Vaginal, anal, and oral sex with an infected person.
  • Skin-to-skin contact: Through close skin contact in the genital area, even without complete penetration.
  • Autoinoculation: Less common, but a person can transfer the virus from one part of their body to another.
Anal Warts:
  • Caused by: Mainly HPV types 6 and 11.
  • Transmission:
  • Sexual contact: Anal sex with an infected person.
  • Skin-to-skin contact: Similar to the transmission of genital warts.
Oral Warts (mouth and throat):
  • Caused by: HPV types 6, 11, 16, and 18.
  • Transmission:
  • Oral sex: Oral-genital contact with an infected person.
  • Deep kissing: In rare cases, mouth-to-mouth contact can transmit the virus if there are microlesions in the mucosa.
Common Warts (verruca vulgaris):
  • Caused by: HPV types 1, 2, 4, 27, and 57.
  • Transmission:
  • Direct contact: Direct touch with warts from another person.
  • Indirect contact: Sharing objects like towels, manicure tools, or contaminated surfaces.
Plantar Warts:
  • Caused by: HPV types 1, 2, 4, and 63.
  • Transmission:
  • Direct contact: With a plantar wart from another person.
  • Contaminated surfaces: Walking barefoot in public areas like pools, showers, and gyms.
Flat Warts:
  • Caused by: HPV types 3, 10, 28, and 49.
  • Transmission:
  • Direct contact: With a flat wart from another person.
  • Autoinoculation: Through scratching, spreading the virus to other parts of the body.

Conclusion

The contagion of HPV and the appearance of warts depend on the type of HPV and the location of the infection. Prevention through vaccination and safe sexual and hygiene practices is key to reducing the risk of transmission.

Symptons of Being Infected with HPV

Symptoms in the Genital Area

Human Papillomavirus (HPV) can cause various symptoms in the genitals of both men and women, although many people may not show evident symptoms. Here are the most common symptoms for each gender:

Symptoms in Men:
  • Genital warts: Small warts or bumps on the penis, scrotum, anal area, or around the anus.
  • Flat lesions: Small, flat spots, sometimes hard to see, on the penis or anal area.
  • Irritation or itching: Itching or irritation in the affected areas.
  • Pain or discomfort: Pain during sex or urination, though this is less common.
Symptoms in Women:
  • Genital warts: Warts on the vulva, vagina, cervix, anal area, or around the anus.
  • Flat lesions: Flat spots on the vulva, cervix, or anal area, sometimes not visible to the naked eye.
  • Changes in vaginal discharge: Abnormal discharge that may indicate changes in the cervix.
  • Pain or discomfort: Pain during sex or urination.
  • Abnormal bleeding: Vaginal bleeding outside of the menstrual period, especially after intercourse.
General Considerations:
  • Asymptomatic: Many people with HPV do not show visible symptoms but can still transmit the virus to others.
  • Detection and prevention: Regular check-ups and screenings, especially for women, such as Pap tests and HPV tests, are crucial. HPV vaccination is an effective preventive measure for both genders.
  • Consultation: If an HPV infection is suspected, it is important to consult a healthcare professional for proper diagnosis and treatment.

Symptoms in the Mouth and Throat

HPV can infect the mouth and throat, and symptoms can vary. Some people may not show visible symptoms, while others may experience the following:

  • Warts: Small warts or bumps in the mouth, lips, tongue, throat, or tonsils.
  • Oral lesions: Red or white spots on the mucous membrane of the mouth.
  • Pain or discomfort: Persistent sore throat, discomfort when swallowing, or feeling like something is stuck in the throat.
  • Hoarseness: Changes in voice, such as hoarseness without an apparent cause.
  • Swelling: Swollen lymph nodes in the neck.

It is important to consult a healthcare professional if these symptoms occur, as they may indicate an HPV infection or other medical conditions. Early detection and appropriate treatment are crucial to preventing complications.

Symptoms in the Cervix

HPV can infect the cervix and often does not cause visible symptoms until the infection progresses. However, some signs and symptoms may indicate the presence of HPV in the cervix:

  • Asymptomatic: Most HPV infections in the cervix do not show symptoms in the early stages. This is especially common and one of the reasons why screenings are crucial.
  • Precancerous or cancerous lesions: In advanced cases, HPV can cause cellular changes in the cervix that can lead to cervical cancer if not detected and treated in time.
  • Abnormal vaginal bleeding: Bleeding outside of the regular menstrual cycle, after sexual intercourse, or after menopause.
  • Abnormal vaginal discharge: Unusual discharge, which may be watery, thick, or have an unpleasant odor.
  • Pain during sexual intercourse: Pain or discomfort during sex, known as dyspareunia.
  • Pelvic pain: Constant or recurring pelvic pain, though this symptom is less common.

How Long Does HPV Live Outside the Human Body?

HPV does not survive long outside the human body. While there is no exact consensus on the specific duration HPV can remain viable on surfaces, most studies and experts suggest the virus has limited survival outside its host.

Factors Affecting HPV Survival Outside the Body:
  • Type of surface:
  • Dry and hard surfaces: HPV tends to deactivate more quickly on dry, hard surfaces.
  • Moist and porous surfaces: It can survive a bit longer in moist environments and porous materials, though still for a relatively short period.
  • Environmental conditions:
  • Temperature: HPV is sensitive to extreme temperatures and survives better at temperatures close to the human body.
  • Humidity: A humid environment can slightly prolong its viability, but not significantly.
  • Ultraviolet (UV) light: Exposure to direct sunlight and UV light can inactivate the virus quickly.
Survival in Specific Studies:
  • Some studies have indicated that HPV can remain viable for hours or even days under ideal laboratory conditions, but in everyday life, conditions are usually not ideal for its prolonged survival.
  • One specific study found that HPV could survive up to 24 hours on non-porous surfaces like metal or plastic under laboratory conditions, but the virus’s infectivity decreases significantly over time.

Conclusion:

HPV has a limited life outside the human body, and its ability to cause an infection decreases rapidly in non-ideal environments. However, maintaining good hygiene and disinfection practices can help further reduce the risk of indirect contagion.

Importance of Early Detection

Since HPV infections in the cervix are often asymptomatic, regular screenings are essential. These include:

  • Pap test (Pap smear): Detects precancerous changes in cervical cells.
  • HPV test: Detects the presence of human papillomavirus in the cervix.

HPV vaccination is an important preventive measure to reduce the risk of infections and the development of cervical cancer. Consulting a gynecologist for regular check-ups and following screening recommendations is crucial for cervical health.

Natural Remedies

Natural Defense Against HPV

To date, there is no definitive cure to completely eliminate HPV from the body, as it is a virus that can persist in the organism latently even after visible symptoms have disappeared.

Natural Strategies

However, there are some natural strategies that may help strengthen the immune system and reduce viral load, which can aid in managing symptoms and preventing future outbreaks. Some of these natural remedies include:

Healthy diet: Consuming a diet rich in fruits, vegetables, whole grains, and lean proteins can help strengthen the immune system and combat viral infections, including HPV.

Nutritional supplements: Some supplements such as zinc, vitamin C, vitamin E, folic acid, and selenium may help strengthen the immune system and combat HPV. However, it’s important to consult with a doctor before starting any supplement.

Medicinal herbs: Some herbs like astragalus, echinacea, garlic, and propolis have antiviral properties and may help reduce HPV viral load.

Stress reduction: Chronic stress can weaken the immune system and increase susceptibility to viral infections. Practicing stress management techniques such as meditation, yoga, or deep breathing can help reduce HPV viral load.

Avoiding tobacco and alcohol: Tobacco and alcohol can weaken the immune system and increase the risk of developing HPV-related health problems. Avoiding tobacco and limiting alcohol consumption can help reduce HPV viral load.

It’s important to note that these natural remedies are not a definitive cure for HPV and should not replace medical advice or treatment prescribed by a healthcare professional. If you have genital warts or other HPV-related symptoms, it’s important to speak with a doctor for proper diagnosis and an appropriate treatment plan.

Healthy Diet

Here are some tips on natural remedies from within the body that can help:

Balanced Diet: Consuming a balanced and nutrient-rich diet is essential for maintaining a strong immune system. This includes foods such as fruits, vegetables, whole grains, lean proteins, and healthy fats.

Increase Antioxidant Intake: Antioxidants help combat oxidative stress in the body, which can strengthen the immune system. Some antioxidant-rich foods include berries, broccoli, spinach, nuts, and seeds.

Include Foods Rich in Vitamin C: Vitamin C is known for its ability to strengthen the immune system. Increase intake of foods rich in vitamin C, such as citrus fruits, bell peppers, strawberries, kiwi, and broccoli.

Consume Foods Rich in Zinc: Zinc is an important mineral for proper immune function. Some sources of zinc include beef, chicken, seafood, nuts, seeds, and legumes.

Adding Garlic to Your Diet: Garlic has antimicrobial and antiviral properties that can help fight viral infections like HPV. Try adding fresh garlic to your meals or consider taking garlic supplements if necessary.

Including Probiotics: Probiotics are beneficial bacteria that can help maintain a healthy balance of bacteria in the gut and strengthen the immune system. Probiotic-rich foods include yogurt, kefir, sauerkraut, kimchi, and tempeh.

Reducing Sugar Intake: Excess sugar can weaken the immune system and promote inflammation in the body. Try to limit consumption of processed and sugary foods, and opt for healthier carbohydrate sources like fruits, vegetables, and whole grains.

Drinking Enough Water: Staying hydrated is important for proper immune function and for flushing toxins from the body. Make sure to drink enough water throughout the day.

Filiform Warts

These warts look like long threads that stick out. They often grow on your face around your mouth, eyes and nose, but they can also occur on the neck or elsewhere on the body. Like other types of warts, filiform warts are caused by the human papillomavirus (HPV). HPV types 1, 2, 4, 27 and 29 cause filiform warts.

They are usually harmless, but they can be unsightly or cause discomfort, especially if they develop in areas prone to friction or irritation. Filiform warts can sometimes bleed if they are scratched or injured.

Appearance

They are characterized by long, narrow projections that resemble tiny threads or filaments. These warts can be flesh-colored, pink, or light brown.

+Info Results

Understanding HPV Medical Results

Understanding the meaning of a positive HPV test result is crucial for individuals receiving their screening outcomes. Here’s a more detailed breakdown about some specific information in your results sheet.

Colposcopy – Biopsy

Cervix division

To divide the surface of the cervix for reference and description purposes during medical examinations, such as colposcopy, refers to the way healthcare professionals locate and describe specific areas of the cervix more accurately. This technique assists healthcare professionals in pinpointing and describing specific areas of the cervix with greater precision.

In order to report findings, cervix can be divided:

  • in quarters
  • clockwise, using the o’clock position

Difference between the endocervix and the cervix?

The ectocervix (also called exocervix) is the outer part of the cervix that can be seen during a gynecologic exam. The ectocervix is covered with thin, flat cells called squamous cells. The endocervix is the inner part of the cervix that forms a canal that connects the vagina to the uterus. The endocervix is covered with column-shaped glandular cells that make mucus.

The squamocolumnar junction (also called the transformation zone) is the border where the endocervix and ectocervix meet. Most cervical cancers begin in this area.

Anatomy of the cervix.

The cervix is the lower, narrow end of the uterus that connects the uterus to the vagina. It is made up of the internal OS (the opening between the cervix and the upper part of the uterus), the endocervix (the inner part of the cervix that forms the endocervical canal), the ectocervix (the outer part of the cervix that opens into the vagina) and the external OS (the opening between the cervix and vagina).

The area where the endocervix and ectocervix meet is called the squamocolumnar junction, which contains both glandular cells (column-shaped cells that make mucus) from the endocervix and squamous cells (thin, flat cells) from the ectocervix. The squamocolumnar junction is sometimes referred to as the transformation zone.

Source: cancer.gov

Colposcopy and IUD

Colposcopy can be performed with an intrauterine device (IUD) in place. How- ever, if a loop electrosurgical excision procedure (LEEP) is subsequently re- quired for treatment of cervical dyspla- sia, the IUD is usually removed to facili- tate excision of the cervical tissue

Colposcopic assessment

The colposcopic diagnosis of cervical neoplasia depends on the recognition of four main features: intensity (colour tone) of acetowhitening, margins and surface contour of acetowhite areas, vascular features and colour changes after iodine application.

The colposcopic features that differentiate an abnormal transformation zone from the normal include the following: colour tone of acetowhite areas; surface pattern of acetowhite areas; borderline between acetowhite areas and the rest of the epithelium; vascular features and colour changes after application of iodine.

  • Low-grade CIN is often seen as thin, smooth acetowhite lesions with well-demarcated, but irregular, feathery or digitating or angular margins.
    • Vascular features, such as fine punctation and/or fine mosaics in acetowhite areas, may be associated with low-grade CIN.
  • High-grade CIN are associated with thick, dense, dull, opaque or greyish-white acetowhite areas with well-demarcated, regular margins, which sometimes may be raised and rolled out. They may be more extensive and complex lesions extending into the endocervical canal. The surface contour of the acetowhite areas associated with high-grade CIN lesions tend to be less smooth, or irregular and nodular. Visualization of one or more borders within an acetowhite lesion or an acetowhite lesion with varying colour intensity is associated with high-grade lesions.
    • Coarse punctation and/or coarse mosaics in acetowhite areas tend to occur in high-grade lesions.

Saline solution

Following application of saline, abnormal epithelium may appear much darker than the normal epithelium.

  • Condylomata
  • Leukoplakia or hyperkeratosis
  • Vasculature
  • Capillaries
  • Fine punctuation, fine mosaics
  • Coarse punctation and coarse mosaics

5% acetic acid solution

The observation of a well demarcated, dense, opaque, acetowhite area closer to or abutting the squamocolumnar junction in the transformation zone after application of 5% acetic acid is critical.

In fact, it is the most important of all colposcopic signs, and is the hallmark of colposcopic diagnosis of cervical neoplasia.

Lugol’s iodine solution

Normal vaginal and cervical squamous epithelium and mature metaplastic epithelium contain glycogen-rich cells, and thus take up the iodine stain and turn black or brown.

Dysplastic epithelium contains little or no glycogen, and thus does not stain with iodine and remains mustard or saffron yellow

Cervix appearance HPV positive: Schiller Test

Source: WHO

Results in Saline solution

Condylomata, multiple, exophytic lesions, that are infrequently found on the cervix, but more commonly in the vagina or on the vulva.

Leukoplakia or hyperkeratosis, a white, well-demarcated area on the cervix due to the presence of keratin usually idiopathic, but it may also be caused by chronic foreign body irritation, HPV infection or squamous neoplasia

Vasculature, abnormal vasculature patterns is before the application of acetic acid, the effect of which may obscure some or all of the changes, especially in an acetowhite area. The abnormalities of interest are punctation, mosaics and atypical vessels

Capillaries, when CIN develops as a result of HPV infection and atypical metaplasia, the afferent and efferent capillary system may be trapped (incorporated) into the diseased dysplastic epithelium through several elongated stromal papillae and a thin layer of epithelium may remain on top of these vessels.

Fine punctation refers to looped capillaries – viewed end-on – that appear to be of fine calibre and located close to one another, producing a delicate stippling effect. Fine mosaics are a network of fine-calibre blood vessels that appear in close proximity to one another, as a mosaic pattern, when viewed with the colposcope.

Coarse punctation and coarse mosaics are formed by vessels having larger calibre and larger intercapillary distances, in contrast to the corresponding fine changes.

Visual inspection after application of acetic acid (VIA)

Visual inspection after application of acetic acid (VIA) involves naked-eye examination of the uterine cervix with appropriate illumination after application of freshly prepared 3%–5% acetic acid. The interpretation of the test is based on the detection of a well-defined dense acetowhite area on the transformation zone of the cervix one minute after application of acetic acid. VIA is a screening test that aims to detect cervical pre-cancers and early cervical cancers in apparently normal and asymptomatic women.

Determining the nature of the lesion

The colposcopic detection of CIN essentially involves recognizing the following characteristics: the colour tone, margin and surface contour of the acetowhite epithelium in the transformation zone, as well as the arrangement of the terminal vascular bed and iodine staining. 

Colposcopy Manual

Colposcopy and Treatment of Cervical Intraepithelial Neoplasia:
A Beginners’ Manual

By WHO

HPV Test – Pap Smear

Many HPV tests simultaneously provide information on the presence of at least a few selected HPV genotypes (partial genotyping). If the sample is positive for high-risk HPV, such test results will at least indicate whether HPV16 or HPV18 are present in the sample, because these are the most oncogenic HPV types. Some of the tests may provide information on the presence of additional HPV types (e.g. HPV45).

The Pap test (also called a Pap smear or cervical cytology) collects cervical cells so they can be checked for changes caused by HPV that may—if left untreated—turn into cervical cancer.

Squasmous cells

Squamous cells are a type of epithelial cell that forms the outer layer of the skin and mucous membranes, including the lining of the cervix.

In the context of HPV, squamous cells are particularly relevant to cervical health. HPV is a group of viruses that can infect the genital area, including the cervix. Persistent infection with high-risk types of HPV is a significant risk factor for the development of cervical abnormalities, including squamous cell changes.

HPV can cause alterations in the structure and function of squamous cells in the cervix, leading to various abnormalities, such as squamous metaplasia, dysplasia, or in more severe cases, cervical intraepithelial neoplasia (CIN) or cervical cancer. Regular cervical screenings, such as Pap smears and HPV testing, are essential for detecting these changes early and preventing the progression to more severe conditions.

p16/Ki-67

They are is a combination stain used in pathology to assess the activity of cells, particularly in the context of cervical cancer screening and diagnosis.

When p16 and Ki-67 are used together in a staining technique, it can help pathologists assess whether there are abnormal changes in the cells, especially in the cervix. The presence of both increased p16 and Ki-67 staining can indicate potential abnormalities or dysplasia, suggesting that the cells are actively dividing and may be undergoing precancerous changes.

This staining combination is often used in the interpretation of cervical biopsies or Pap smears to assist in the diagnosis and grading of cervical lesions, helping healthcare professionals to identify whether further investigation or intervention is needed. The results can provide valuable information in the management of cervical health and the prevention of cervical cancer.

Let’s break down the components:

p16:

p16 is a protein that regulates the cell cycle. In normal cells, p16 helps prevent excessive cell division. However, in the presence of certain infections, such as high-risk types of human papillomavirus (HPV), p16 expression can be increased.

Ki-67:

Ki-67 is a protein that is present in cells only during active phases of the cell cycle (such as during cell division). It serves as a marker for cellular proliferation or growth. The more Ki-67 is present, the more actively the cells are dividing.

From metaplasia to dysplasia to neoplasia

Focal squamous metaplasia refers to a localized transformation of one type of epithelial cell into another type known as squamous cells. Epithelial cells are the building blocks of various tissues in the body, including the lining of the cervix.

Squamous metaplasia is a common finding in the cervix and other tissues. It is often seen as part of the body’s response to irritation or inflammation. In the context of cervical health, squamous metaplasia can occur due to various factors, including infections, hormonal changes, or other irritations.

Dysplasia refers to abnormal changes in the cells, and in the context of the cervix, it is often associated with precancerous or potentially cancerous changes. When there is persistent irritation or infection, such as with certain types of human papillomavirus (HPV), it can lead to changes in the cervical cells.

The progression from squamous metaplasia to dysplasia involves a spectrum of changes in cell morphology and behavior. While squamous metaplasia itself is generally considered a benign process, if the irritation or infection persists, it can contribute to the development of dysplastic changes.

In the context of medical terms like metaplasia, dysplasia, and neoplasia, the suffix “-plasia” refers to cellular growth or development. In summary, the suffix “-plasia” in these medical terms indicates changes in cellular development or growth, whether it be a change in cell type (metaplasia), abnormal organization of cells (dysplasia), or uncontrolled cellular growth (neoplasia). Here’s a brief explanation of how this suffix is used in each of the mentioned terms:

Metaplasia:

“Meta-” means change, and “-plasia” refers to cellular development or growth.

  • Metaplasia is a reversible change in which one type of adult cell is replaced by another type of adult cell.
  • It is often a response to chronic irritation or inflammation.
  • In the context of the cervix, squamous metaplasia is a common finding.

Dysplasia:

“Dis-” means abnormal or malformed, and again, “-plasia” refers to cellular development.

  • Dysplasia refers to the abnormal development or growth of cells, tissues, or organs.
  • It involves a disorganized arrangement of cells and is considered a pre-cancerous condition.
  • In the cervix, dysplasia is often graded as mild, moderate, or severe based on the degree of abnormality in the cells.
  • Dysplasia can be detected through cervical screenings like Pap smears and confirmed by further diagnostic procedures such as colposcopy and biopsy.

Neoplasia:

“Neo-” means new, and once again, “-plasia” refers to cellular growth.

  • Neoplasia is the uncontrolled, abnormal growth of cells, commonly referred to as a tumor or mass.
  • Neoplasia can be either benign or malignant (cancerous).
  • In the cervix, severe dysplasia (CIN 3) or carcinoma in situ may progress to invasive cervical cancer, representing a transition from pre-cancerous to cancerous changes.

E6/E7

HPVs encode two oncoproteins, E6 and E7, which are directly responsible for the development of HPV-induced carcinogenesis. They do this cooperatively by targeting diverse cellular pathways involved in the regulation of cell cycle control, of apoptosis and of cell polarity control networks.

The terms E6 and E7 refer to specific viral proteins produced by high-risk types of the human papillomavirus (HPV), particularly those associated with an increased risk of cervical cancer. Understanding the roles of E6 and E7 proteins is crucial in the context of HPV-related cancers, particularly cervical cancer. Detection of E6 and E7 activity or their presence in cells can be used in laboratory tests as biomarkers for the identification of high-risk HPV infections and assessing the potential risk of cancer development. Testing for E6 and E7 is often used in research and clinical settings for the management and monitoring of HPV-related diseases.

Here is a brief explanation of E6 and E7 in the context of HPV:

E6 Protein:

  • The E6 protein is a viral oncoprotein produced by high-risk HPV types.
  • It plays a crucial role in the ability of the virus to promote the development of cancer.
  • E6 has the ability to bind to and degrade the tumor suppressor protein p53, which normally helps regulate cell growth and prevent the formation of tumors.
  • By inhibiting p53, E6 allows infected cells to evade normal regulatory mechanisms and increases the risk of uncontrolled cell growth, a hallmark of cancer.

E7 Protein:

  • Similar to E6, the E7 protein is another viral oncoprotein produced by high-risk HPV types.
  • E7 primarily targets the retinoblastoma (Rb) tumor suppressor protein.
  • By interacting with and inactivating Rb, E7 disrupts the normal control of the cell cycle, promoting cell proliferation.
  • The inactivation of Rb contributes to the abnormal growth and potential transformation of cells, leading to the development of cancer.

“Dyskaryosis” vs “Dysplasia”

The terms “dyskaryosis” and “dysplasia” are related, and both are used in the context of evaluating cellular abnormalities, especially in cervical cytology (Pap smears) and histopathology. However, they refer to different aspects of cell changes, and the severity of these changes is often classified into different grades.

  • Dyskaryosis specifically refers to abnormal changes in the cell nucleus, the central part of a cell that contains genetic material.
  • Severity: The term itself does not inherently indicate severity but rather the presence of abnormal nuclear features. In the context of cervical cytology, dyskaryosis is often associated with the potential for pre-cancerous or cancerous changes.
  • Dysplasia refers to abnormal development or growth of cells, tissues, or organs, involving disordered cellular organization and structure.
  • Severity: Dysplasia is often graded as mild, moderate, or severe, depending on the extent and severity of cellular abnormalities. In cervical pathology, this is commonly referred to as cervical dysplasia. Mild dysplasia may indicate early changes, while severe dysplasia may be more advanced and closer to a cancerous state.

The presence of dyskaryosis or dysplasia does not necessarily mean cancer is present, but it does indicate the need for further evaluation and monitoring. Healthcare professionals will often recommend additional tests or procedures, such as colposcopy or biopsy, to assess the severity of the changes and determine the appropriate course of action.

Other texts in your results sheet

Squamous Papilloma:

   – Definition: Squamous papilloma is a type of benign (non-cancerous) growth or tumor in squamous epithelial tissue. It often presents as a wart-like or finger-like projection.

   – Implication: In this context, the presence of squamous papilloma indicates a benign growth, suggesting that the changes observed are not cancerous.

Inflammation:

   – Definition: Inflammation refers to the body’s response to injury, infection, or irritation, characterized by redness, swelling, heat, and pain.

   – Implication: The mention of inflammation suggests that there is an inflammatory response in the examined tissue. Inflammation can be a reaction to various factors, including infections or irritations.

Reactive Basal Atypia:

   – Definition: Basal atypia refers to abnormal changes in the basal (bottom) layer of epithelial cells. “Reactive” often implies changes that are a response to some form of irritation or injury.

   – Implication: The term “reactive” suggests that the observed basal atypia may be a response to the inflammatory process. It’s important to note that “reactive” changes are usually non-cancerous.

Presence of a Few Mitotic Figures:

   – Definition: Mitotic figures are cells undergoing the process of cell division (mitosis).

   – Implication: The presence of a few mitotic figures may indicate cellular activity, which is not uncommon in areas with inflammation. However, the mention of “a few” suggests that the mitotic activity is not excessively high.

No High Grade Dysplasia or Malignancy:

   – High Grade Dysplasia: Refers to more severe and abnormal cellular changes.

   – Malignancy: Indicates the presence of cancerous cells.

   – Implication: The absence of high-grade dysplasia or malignancy is a positive aspect of the report. It suggests that the observed changes are not indicative of pre-cancerous or cancerous conditions.

Prevention

Guardians Against HPV: Comprehensive Guide to Prevention, Vaccination, and Screening

Human Papillomavirus (HPV) is a common sexually transmitted infection that can have serious health consequences. Effective prevention strategies include a combination of measures, vaccination, and screening tests. Understanding and adopting these preventive measures is crucial in reducing the risk of HPV-related complications.

Vaccination

While HPV vaccines can have side effects, they are typically mild and temporary. The benefits of vaccination, in terms of preventing cancers and other HPV-related diseases, far outweigh the risks of side effects. It is important to discuss any concerns with a healthcare professional to make an informed decision about vaccination.

Safe Practices: Minimizing Transmission Risks

Safe Sex Practices:

  • Consistent and correct condom use during sexual activity can reduce the risk of HPV transmission, though it may not eliminate it entirely.
  • Limiting the number of sexual partners and choosing partners with lower risk can also lower the likelihood of HPV exposure.

Can oral sex impact in the genital area?

Yes, oral sex can transmit certain strains of the human papillomavirus (HPV) to the genital area. While the risk of HPV transmission through oral sex may be lower than through vaginal or anal intercourse, it is still possible.

It’s essential to use protection, such as condoms or dental dams, during oral sex to reduce the risk of HPV transmission and other sexually transmitted infections (STIs). Additionally, vaccination against HPV can significantly reduce the risk of infection with the most common cancer-causing strains of the virus.

Screening Tests: Detecting and Managing Infections

Pap Smears and HPV Tests:

  • Pap smears (Pap tests) are used to detect abnormal cervical cells, often caused by HPV infection.
  • HPV tests specifically check for the presence of the virus in cervical cells.
  • Regular screenings are crucial for early detection, enabling timely intervention and preventing the progression of HPV-related diseases.

Vaccinated Individuals and Screening:

  • Even if vaccinated, individuals are advised to continue with routine screenings as vaccines do not cover all HPV types.
  • Screening remains a vital component of overall preventive healthcare.

By combining vaccination, safe sexual practices, and regular screenings, individuals can take proactive steps to prevent HPV-related health issues. Public health efforts focused on education and awareness further contribute to a comprehensive approach in reducing the burden of HPV infections and related diseases.

Source: Nature

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.

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