A koilocyte is a squamous epithelial cell that has undergone a number of structural changes, which occur as a result of infection of the cell by human papillomavirus (HPV). [1] Identification of these cells by pathologists can be useful in diagnosing various HPV-associated lesions.
Koilocytosis or koilocytic atypia or koilocytotic atypia are terms used in histology and cytology to describe the presence of koilocytes in a specimen. [1]
Koilocytes may have the following cellular changes:
Collectively, these types of changes are called a cytopathic effect; various types of cytopathic effect can be seen in many different cell types infected by many different viruses. [2] Infection of cells with HPV causes the specific cytopathic effects seen in koilocytes.
The atypical features seen in cells displaying koilocytosis result from the action of the E5 and E6 oncoproteins produced by HPV. These proteins break down keratin in HPV-infected cells, resulting in the perinuclear halo and nuclear enlargement typical of koilocytes. [3] The E6 oncoprotein, along with E7, is also responsible for the dysregulation of the cell cycle that results in squamous cell dysplasia. The E6 and E7 oncoproteins do this by binding and inhibiting the tumor suppressor genes p53 and RB, respectively. This promotes progression of cells through the cell cycle without appropriate repair of DNA damage, resulting in dysplasia. [4] Due to the ability of HPV to cause cellular dysplasia, koilocytes are found in a number of potentially precancerous lesions.[ citation needed ]
Koilocytes can be visualized microscopically when tissue is collected, fixed, and stained. Though koilocytes can be found in lesions in a number of locations, cervical cytology samples, commonly known as Pap smears, frequently contain koilocytes. [5] In order to visualize koilocytes collected from the cervix, the tissue is stained with the Papanicolaou stain. [5] Another way koilocytes can be visualized is by fixation of tissue with formalin and staining with hematoxylin and eosin, commonly known as H&E. [5] These stains give the cytoplasm and nuclei of cells characteristic colors and allows for visualization of the nuclear enlargement and irregularity, hyperchromasia, and perinuclear halo that are typical of koilocytes.[ citation needed ]
Koilocytes may be found in potentially precancerous cervical, oral and anal lesions.
When examining cytologic specimens, a diagnosis of ASC-US is given if squamous cells are suspicious for low-grade squamous intraepithelial lesion (LSIL) but do not fulfill the criteria. This may be due to limitations in the quality of the specimen, or because the abnormalities in the cells are milder than that seen in LSIL. [6] Cells in this category display koilocyte-like changes such as vacuolization, but not enough changes to definitively diagnose as LSIL. [6] A diagnosis of ASC-US warrants further follow-up to better characterize the extent of the abnormal cells. [4]
In LSIL of the cervix, definitive koilocytes are present. In addition, squamous cells commonly display binucleation and mitoses are present, signifying increased cellular division. [7] However, these changes are primarily limited to upper cell layers in the epithelium, no mitoses are found higher than the lower one third of epithelium, and the basal layer of cells remains a discrete layer. This differentiates this lesion from high-grade squamous intraepithelial lesion (HSIL) of the cervix. [7]
Verruca vulgaris, or common warts, may arise in the oral mucosa. These lesions are associated with HPV subtypes 1, 6, 11, and 57. [8] Histopathology of these lesions displays koilocytes in the epithelium. [8]
Approximately 50 percent of oropharyngeal cancers are associated with HPV infection. [4] Koilocytosis is the most common cytopathic effect present in HPV-related oropharyngeal cancers. [9] However, the current standard of care for these tumors includes verification of HPV status using methodologies other than the histopathologic presence or absence of koilocytes alone. [10] These methodologies include polymerase chain reaction (PCR), in situ hybridization (ISH), and immunohistochemistry (IHC). [10]
Histopathologic changes seen in LSIL of the cervix can also be seen in anal epithelium. Koilocytes are characteristic of LSIL in the anus. In contrast to LSIL, HSIL in the anus consists of abnormal basaloid cells replacing more than half of the anal epithelium. [11]
These changes occur in the presence of human papillomavirus and occasionally can lead to cervical intraepithelial neoplasia, and if left untreated some may eventually progress to malignant cancer.[ citation needed ]
The cervix or cervix uteri is a dynamic fibromuscular organ of the female reproductive system that connects the vagina with the uterine cavity. The human cervix has been documented anatomically since at least the time of Hippocrates, over 2,000 years ago. The cervix is approximately 4 cm long with a diameter of approximately 3 cm and tends to be described as a cylindrical shape, although the front and back walls of the cervix are contiguous. The size of the cervix changes throughout a women's life cycle. For example, during their fertile years of the reproductive cycle, females tend to have a larger cervix vis á vis postmenopausal females; likewise, females who have produced offspring have a larger sized cervix than females who have not produced offspring.
The Papanicolaou test is a method of cervical screening used to detect potentially precancerous and cancerous processes in the cervix or, more rarely, anus. Abnormal findings are often followed up by more sensitive diagnostic procedures and, if warranted, interventions that aim to prevent progression to cervical cancer. The test was independently invented in the 1920s by the Greek physician Georgios Papanikolaou and named after him. A simplified version of the test was introduced by the Canadian obstetrician Anna Marion Hilliard in 1957.
Cervical cancer is a cancer arising from the cervix or in the any layer of the wall of the cervix. It is due to the abnormal growth of cells that have the ability to invade or spread to other parts of the body. Early on, typically no symptoms are seen. Later symptoms may include abnormal vaginal bleeding, pelvic pain or pain during sexual intercourse. While bleeding after sex may not be serious, it may also indicate the presence of cervical cancer.
Human papillomavirus infection is caused by a DNA virus from the Papillomaviridae family. Many HPV infections cause no symptoms and 90% resolve spontaneously within two years. In some cases, an HPV infection persists and results in either warts or precancerous lesions. These lesions, depending on the site affected, increase the risk of cancer of the cervix, vulva, vagina, penis, anus, mouth, tonsils, or throat. Nearly all cervical cancer is due to HPV, and two strains – HPV16 and HPV18 – account for 70% of all cases. HPV16 is responsible for almost 90% of HPV-positive oropharyngeal cancers. Between 60% and 90% of the other cancers listed above are also linked to HPV. HPV6 and HPV11 are common causes of genital warts and laryngeal papillomatosis.
Colposcopy is a medical diagnostic procedure to visually examine the cervix as well as the vagina and vulva using a colposcope.
Anal cancer is a cancer which arises from the anus, the distal opening of the gastrointestinal tract. Symptoms may include bleeding from the anus or a lump near the anus. Other symptoms may include pain, itchiness, or discharge from the anus. A change in bowel movements may also occur.
Oral leukoplakia is a potentially malignant disorder affecting the oral mucosa. It is defined as "essentially an oral mucosal white lesion that cannot be considered as any other definable lesion." Oral leukoplakia is a white patch or plaque that develops in the oral cavity and is strongly associated with smoking. Leukoplakia is a firmly attached white patch on a mucous membrane which is associated with increased risk of cancer. The edges of the lesion are typically abrupt and the lesion changes with time. Advanced forms may develop red patches. There are generally no other symptoms. It usually occurs within the mouth, although sometimes mucosa in other parts of the gastrointestinal tract, urinary tract, or genitals may be affected.
Squamous metaplasia is a benign non-cancerous change (metaplasia) of surfacing lining cells (epithelium) to a squamous morphology.
A precancerous condition is a condition, tumor or lesion involving abnormal cells which are associated with an increased risk of developing into cancer. Clinically, precancerous conditions encompass a variety of abnormal tissues with an increased risk of developing into cancer. Some of the most common precancerous conditions include certain colon polyps, which can progress into colon cancer, monoclonal gammopathy of undetermined significance, which can progress into multiple myeloma or myelodysplastic syndrome. and cervical dysplasia, which can progress into cervical cancer. Bronchial premalignant lesions can progress to squamous cell carcinoma of the lung.
Cervical intraepithelial neoplasia (CIN), also known as cervical dysplasia, is the abnormal growth of cells on the surface of the cervix that could potentially lead to cervical cancer. More specifically, CIN refers to the potentially precancerous transformation of cells of the cervix.
Vacuolization is the formation of vacuoles or vacuole-like structures, within or adjacent to cells. Perinuclear vacuolization of epidermal keratinocytes is most likely inconsequential when not observed in combination with other pathologic findings. In dermatopathology "vacuolization" often refers specifically to vacuoles in the basal cell-basement membrane zone area, where it is an unspecific sign of disease. It may be a sign of for example vacuolar interface dermatitis, which in turn has many causes.
Bovine papillomaviruses (BPV) are a paraphyletic group of DNA viruses of the subfamily Firstpapillomavirinae of Papillomaviridae that are common in cattle. All BPVs have a circular double-stranded DNA genome. Infection causes warts of the skin and alimentary tract, and more rarely cancers of the alimentary tract and urinary bladder. They are also thought to cause the skin tumour equine sarcoid in horses and donkeys.
Dyskaryosis (dis-kār-ĭ-ó-sis) is abnormal cytologic changes of squamous epithelial cells characterized by hyperchromatic nuclei and/or irregular nuclear chromatin. This may be followed by the development of a malignant neoplasm. Dyskaryosis is used synonymously with dysplasia, which is the more common term. The term "dyskaryosis" is not to be confused with "dyskeratosis".
A squamous cell papilloma is a generally benign papilloma that arises from the stratified squamous epithelium of the skin, lip, oral cavity, tongue, pharynx, larynx, esophagus, cervix, vagina or anal canal. Squamous cell papillomas are typically associated with human papillomavirus (HPV) while sometimes the cause is unknown.
HspE7 is an investigational therapeutic vaccine candidate being developed by Nventa Biopharmaceuticals for the treatment of precancerous and cancerous lesions caused by the human papillomavirus (HPV). HspE7 uses recombinant DNA technology to covalently fuse a heat shock protein (Hsp) to a target antigen, thereby stimulating cellular immune system responses to specific diseases. HspE7 is a patented construct consisting of the HPV Type 16 E7 protein and heat shock protein 65 (Hsp65) and is currently the only candidate using Hsp technology to target the over 20 million Americans already infected with HPV.
An anal Pap smear is the anal counterpart of the cervical Pap smear. It is used for the early detection of anal cancer. Some types of human papillomavirus (HPV) can cause anal cancer. Other HPV types cause anogenital warts. Cigarette smokers, men who have sex with men, individuals with a history of immunosuppression and women with a history of cervical, vaginal and vulval cancer are at increased risk of getting anal cancer. Vaccination against HPV before initial sexual exposure can reduce the risk of anal cancer.
The Bethesda system (TBS), officially called The Bethesda System for Reporting Cervical Cytology, is a system for reporting cervical or vaginal cytologic diagnoses, used for reporting Pap smear results. It was introduced in 1988 and revised in 1991, 2001, and 2014. The name comes from the location of the conference, sponsored by the National Institutes of Health, that established the system.
Anal dysplasia is a pre-cancerous condition which occurs when the lining of the anal canal undergoes abnormal changes. It can be classified as low grade squamous intraepithelial lesions (LSIL) and high-grade squamous intraepithelial lesions (HSIL). Most cases are not associated with symptoms, but people may notice lumps in and around the anus.
Cervical cancer screening is a medical screening test designed to identify risk of cervical cancer. Cervical screening may involve looking for viral DNA, and/or to identify abnormal, potentially precancerous cells within the cervix as well as cells that have progressed to early stages of cervical cancer. One goal of cervical screening is to allow for intervention and treatment so abnormal lesions can be removed prior to progression to cancer. An additional goal is to decrease mortality from cervical cancer by identifying cancerous lesions in their early stages and providing treatment prior to progression to more invasive disease.
Microglandular hyperplasia (MGH) of the cervix is an epithelial benign abnormality (lesion) associated with gland proliferation. It can terminate in mature squamous metaplasia, and it is suspected reserve cells are involved in this process, perhaps in the form of reserve cell hyperplasia with glandular differentiation.
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