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

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.

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