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Deep Learning Technology: Sebastian Arnold, Betty van Aken, Paul Grundmann, Felix A. Gers and Alexander Löser. Learning Contextualized Document Representations for Healthcare Answer Retrieval. The Web Conference 2020 (WWW'20)
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Depending on several factors and the location of the infection, CIN can start in any of the three stage, and can either progress, or regress. The grade of squamous intraepithelial lesion can vary.
CIN is classified in grades:
Usually no treatment is indicated for clinically asymptomatic cervical ectropions. Hormonal therapy may be indicated for symptomatic erosion. If it becomes troublesome to the patient, it can be treated by discontinuing oral contraceptives, cryotherapy treatment, or by using ablation treatment under local anaesthetic. Ablation involves using a preheated probe (100 °C) to destroy 3–4 mm of the epithelium. In post-partum erosion, observation and re-examination are necessary for 3 months after labour.
Treatment for CIN 1, which is mild dysplasia, is not recommended if it lasts fewer than 2 years. Usually when a biopsy detects CIN 1 the woman has an HPV infection which may clear on its own within 12 months, and thus it is instead followed for later testing rather than treated.
Treatment for higher grade CIN involves removal or destruction of the neoplastic cervical cells by cryocautery, electrocautery, laser cautery, loop electrical excision procedure (LEEP), or cervical conization. Therapeutic vaccines are currently undergoing clinical trials. The lifetime recurrence rate of CIN is about 20%, but it isn't clear what proportion of these cases are new infections rather than recurrences of the original infection.
Surgical treatment of CIN lesions is associated with an increased risk of infertility or subfertility, with an odds ratio of approximately 2 according to a case-control study.
The treatment of CIN during pregnancy increases the risk of premature birth.
99% of cervical polyps will remain benign and 1% will at some point show neoplastic change. Cervical polyps are unlikely to regrow.
Cervical polyps can be seen during a pelvic examination as red or purple projections from the cervical canal. Diagnosis can be confirmed by a cervical biopsy which will reveal the nature of the cells present.
The diagnosis is based on tissue examination, e.g. biopsy.
The name of the lesion describes it microscopic appearance. It has nipple-like structures with fibrovascular cores () that are long in relation to their width (villus-like), which are covered with a glandular pseudostratified columnar epithelium.
Treatment of cervical stenosis involves opening or widening the cervical canal. The condition may improve on its own following the vaginal delivery of a baby.
Cervical canal widening can be termporarily achieved by the insertion of dilators into the cervix. If the stenosis is caused by scar tissue, a laser treatment can be used to vaporize the scarring.
Finally, the surgical enlargement of the cervical canal can be performed by hysteroscopic shaving of the cervical tissue.
Cervical ectropion can be associated with excessive but non-purulent vaginal discharge due to the increased surface area of columnar epithelium containing mucus-secreting glands. It may also give rise to post-coital bleeding, as fine blood vessels present within the columnar epithelium are easily traumatised.
Tissue biopsy is usually indicated to rule out other causes of white patches and also to enable a detailed histologic examination to grade the presence of any epithelial dysplasia. This is an indicator of malignant potential and usually determines the management and recall interval. The sites of a leukoplakia lesion that are preferentially biopsied are the areas that show induration (hardening) and erythroplasia (redness), and erosive or ulcerated areas. These areas are more likely to show any dysplasia than homogenous white areas.
Brush biopsy/exfoliative cytology is an alternative to incisional biopsy, where a stiff brush is scraped against the lining of the mouth to remove a sample of cells. This is then made into a smear which can be examined microscopically. Sometimes the biopsy site can be selected with adjunct methods which aim to highlight areas of dysplasia. Toluidine blue staining, where the dye is preferentially retained by dysplastic tissue, is sometimes used, but there is high false positive rate. Other methods involve the use of illuminescence, relying on either the property of normal autoflorescent molecules in mucosa such as collagen and keratin which is lost from areas of dysplasia or carcinoma under blue light, or by initially staining of the mucosa with toluidine blue or dilute acetic acid and examination under white light.
Checking the cervix by the Papanicolaou test, or Pap test, for cervical cancer has been credited with dramatically reducing the number of cases of and mortality from cervical cancer in developed countries. Pap test screening every three to five years with appropriate follow-up can reduce cervical cancer incidence up to 80%. Abnormal results may suggest the presence of precancerous changes, allowing examination and possible preventive treatment. The treatment of low-grade lesions may adversely affect subsequent fertility and pregnancy. Personal invitations encouraging women to get screened are effective at increasing the likelihood they will do so. Educational materials also help increase the likelihood women will go for screening, but they are not as effective as invitations.
According to the 2010 European guidelines, the age at which to start screening ranges between 20 and 30 years of age, but preferentially not before age 25 or 30 years, and depends on burden of the disease in the population and the available resources.
In the United States, screening is recommended to begin at age 21, regardless of age at which a woman began having sex or other risk factors. Pap tests should be done every three years between the ages of 21 and 65. In women over the age of 65, screening may be discontinued if no abnormal screening results were seen within the previous 10 years and no history of CIN 2 or higher exists. HPV vaccination status does not change screening rates. Screening can occur every 5 years between ages 30 and 65 when a combination of cervical cytology screening and HPV testing is used and this is preferred. However, it is acceptable to screen this age group with a Pap test alone every three years. Screening is not beneficial before age 25 as the rate of disease is low. Screening is not beneficial in women older than 60 years if they have a history of negative results. The American Society of Clinical Oncology (ASCO) guideline has recommend for different levels of resource availability.
Liquid-based cytology is another potential screening method. Although it was probably intended to improve on the accuracy of the Pap test, its main advantage has been to reduce the number of inadequate smears from around 9% to around 1%. This reduces the need to recall women for a further smear. The United States Preventive Services Task Force supports screening every 5 years in those who are between 30 and 65 years when cytology is used in combination with HPV testing.
Pap tests have not been as effective in developing countries. This is in part because many of these countries have an impoverished health care infrastructure, too few trained and skilled professionals to obtain and interepret Pap tests, uninformed women who get lost to follow-up, and a lengthy turn-around time to get results. These realities have resulted in the investigation of cervical screening approaches that use fewer resources and offer rapid results such as visual inspection with acetic acid or HPV DNA testing.
There are many other conditions that are similar in appearance and must be ruled out before a diagnosis of erythroplakia is made (see table). Sometimes, a diagnosis is delayed for up to two weeks in order to see if the lesion spontaneously regresses on its own or if another cause can be found. Erythroplakia frequently is associated with dysplasia, and is thus a precancerous lesion.
Treatment involves biopsy of the lesion to identify extent of dysplasia. Complete excision of the lesion is sometimes advised depending on the histopathology found in the biopsy. Even in these cases, recurrence of the erythroplakia is common and, thus, long-term monitoring is needed.
The diagnosis of cervical agenesis can be made by magnetic resonance imaging, which is used to determine the presence or absence of a cervix. Although MRI can detect the absence of a cervix (agenesis), it is unable to show cervical dysgenesis (where the cervix is present, but malformed). Ultrasound is a less reliable imaging study, but it is often the first choice by gynecologists to establish a diagnosis and can identify a hematometra secondary to cervical agenesis.
The treatment is dependent on the stage. As the prognosis of this tumour is usually good, fertility sparing approaches (conization, cervicectomy) may be viable treatment options.
Vaginal intraepithelial neoplasia (VAIN) is a condition that describes premalignant histological findings in the vagina characterized by dysplastic changes.
The disorder is rare and generally has no symptoms. VAIN can be detected by the presence of abnormal cells in a Papanicolaou test (Pap smear).
Like cervical intraepithelial neoplasia, VAIN comes in three stages, VAIN 1, 2, and 3. In VAIN 1, a third of the thickness of the cells in the vaginal skin are abnormal, while in VAIN 3, the full thickness is affected. VAIN 3 is also known as carcinoma in-situ, or stage 0 vaginal cancer.
Infection with certain types of the human papillomavirus ("high-risk types") may be associated with up to 80% of cases of VAIN. Vaccinating girls with HPV vaccine before initial sexual contact has been shown to reduce incidence of VAIN.
One study found that most cases of VAIN were located in the upper third of the vagina, and were multifocal. In the same study, 65 and 10% patients with VAIN also had cervical intraepithelial neoplasia and vulvar intraepithelial neoplasia, respectively.
In another study, most cases of VAIN went into remission after a single treatment, but about 5% of the cases studied progressed into a more serious condition despite treatment.
Cervical stenosis may be present from birth or may be caused by other factors:
- Surgical procedures performed on the cervix such as colposcopy, cone biopsy, or a cryosurgery procedure
- Trauma to the cervix
- Repeated vaginal infections
- Atrophy of the cervix after menopause
- Cervical cancer
- Radiation
- Cervical nabothian cysts
The annual malignant transformation rate of leukoplakia rarely exceeds 1%, i.e. the vast majority of oral leukoplakia lesions will remain benign. A number of clinical and histopathologic features are associated with varying degrees of increased risk of malignant transformation, although other sources argue that there are no universally accepted and validated factors which can reliably predict malignant change. It is also unpredictable to an extent if an area of leukoplakia will disappear, shrink or remain stable.
- Presence and degree of dysplasia (mild, moderate or severe/carcinoma in situ). Dysplasia is the most important predictor of malignant change, and about 10% of leukoplakia lesions show dysplasia when biopsied.
- Leukoplakia located on the floor of the mouth, the posterior and lateral tongue, and the retromolar areas (the region behind the wisdom teeth) have higher risk, whereas white patches in areas such as the top surface of the tongue and the hard palate do not have significant risk. Although these "high risk" sites are recognized, statistically, leukoplakia is more common on the buccal mucosa, alveolar mucosa, and the lower labial mucosa. Leukoplakia of the floor of the mouth and tongue accounts for over 90% of leukoplakias showing dysplasia or carcinoma on biopsy. This is thought to be due to pooling of saliva in the lower part of the mouth, exposing these areas to more carcinogens held in suspension.
- Red lesions (erythroplasia) and mixed red and white lesions (erythroleukoplakia/"speckled leukoplakia") have a higher risk of malignant change than homogenous leukoplakia.
- Verrucous or nodular areas have a higher risk.
- Although smoking increases risk of malignant transformation, smoking also causes many white patches with no dysplasia. This means that statistically, white patches in non smokers have a higher risk.
- Older people with white patches are at higher risk.
- Larger white patches are more likely to undergo malignant transformation than smaller lesions.
- White patches which have been present for a long period of time have higher risk.
- Persons with a positive family history of cancer in the mouth.
- Candida infection in the presence of dysplasia has a small increased risk.
- A change in the appearance of the white patch, apart from a change in the color, has a higher risk. Changes in the lesion such as becoming fixed to underlying tissues, ulceration, cervical lymphadenopathy (enlargement of lymph nodes in the neck), and bone destruction may herald the appearance of malignancy.
- White patches present in combination with other conditions that carry a higher risk (e.g. oral submucous fibrosis), are more likely to turn malignant.
- Although overall, oral cancer is more common in males, females with white patches are at higher risk than men.
Hematometra is usually treated by surgical cervical dilation to drain the blood from the uterus. Other treatments target the underlying cause of the hematometra; for example, a hysteroscopy may be required to resect adhesions that have developed following a previous surgery. If the cause of the hematometra is unclear, a biopsy of endometrial tissue can be taken to test for the presence of a neoplasm (cancer). Antibiotics may be given as prophylaxis against the possibility of infection.
Although hematometra can often be diagnosed based purely on the patient's history of amenorrhea and cyclic abdominal pain, as well as a palpable pelvic mass on examination, the diagnosis can be confirmed by ultrasound, which will show blood pooled in the uterus and an enlargement of the uterine cavity. A pyelogram or laparoscopy may assist in diagnosing any congenital disorder that is suspected to be the underlying cause of the hematometra.
Cervical cancer is staged by the International Federation of Gynecology and Obstetrics (FIGO) staging system, which is based on clinical examination, rather than surgical findings. It allows only these diagnostic tests to be used in determining the stage: palpation, inspection, colposcopy, endocervical curettage, hysteroscopy, cystoscopy, proctoscopy, intravenous urography, and X-ray examination of the lungs and skeleton, and cervical conization.
The first line of therapy after diagnosis typically involves the administration of the combined oral contraceptive pill, medroxyprogesterone acetate or a gonadotropin-releasing hormone agonist to suppress menstruation and thereby relieve pain. Surgically, cervical agenesis has historically been treated through hysterectomy (removal of the uterus) to relieve symptoms caused by hematocolpos (the accumulation of menstrual fluid in the vagina). Other surgical methods of management involve the creation of an anastomotic connection between the uterus and vagina by neovaginoplasty or recanalization of the cervix. Outcomes in these cases are generally poor, since the natural functions of the cervix—such as mucus production and providing a barrier against ascending infection—cannot be replicated. Furthermore, the success rate of uterovaginal anastomosis is less than 50% and most patients require multiple surgeries while many develop cervical stenotis. Despite this, several pregnancies have been reported in women with cervical agenesis who underwent surgical treatment.
The diagnosis is made in asymptomatic pregnant women either by inspection seeing a bluish discolored cervix or, more commonly, by obstetric ultrasonography. A typical non-specific symptom is vaginal bleeding during pregnancy. Ultrasound will show the location of the gestational sac in the cervix, while the uterine cavity is "empty". Cervical pregnancy can be confused with a miscarriage when pregnancy tissue is passing through the cervix.
Histologically the diagnosis has been made by Rubin’s criteria on the surgical specimen: cervical glands are opposite the trophoblastic tissue, the trophoblastic attachment is below the entrance of the uterine vessels to the uterus or the anterior peritoneal reflection, and fetal elements are absent from the uterine corpus. As many pregnancies today are diagnosed early and no hysterectomy is performed, Rubin's criteria can often not be applied.
Nabothian cysts are considered harmless and usually disappear on their own, although some will persist indefinitely. Some women notice they appear and disappear in relation to their menstrual cycle. If a woman is not sure the anomaly she has found on her cervix is a nabothian cyst, a visit to a doctor is recommended to rule out other conditions.
Rarely, nabothian cysts have a correlation with chronic cervicitis, an inflammatory infection of the cervix.
Nabothian cysts are not considered problematic unless they grow very large and present secondary symptoms. A physician may wish to perform a colposcopy or biopsy on a nabothian cyst to check for cancer or other problems. Two methods for removing these cysts include electrocautery and cryofreezing, although new cysts may form after the procedure.
True cervical pregnancies tend to abort; if, however, the pregnancy is located higher in the canal and the placenta finds support in the uterine cavity it can go past the first trimester. With the placenta being implanted abnormally extensive vaginal bleeding can be expected at time of delivery and placental removal. While early cervical pregnancies may abort spontaneously or can be managed with excision, D&C, suturing, electrocautery, and tamponading, by medication such as methotrexate, and/or by uterine artery embolization, a more advanced pregnancy may require a hysterectomy to control bleeding. The more advanced the pregnancy the higher the risk for a major bleeding necessitating a hysterectomy.
On a very rare occasion, a cervical pregnancy results in the birth of a live baby, typically the pregnancy is in the upper part of the cervical canal and manages to extend into the lower part of the uterine cavity.
A cervical pregnancy can develop together with a normal intrauterine pregnancy; such a heterotopic pregnancy will call for expert management as to not to endanger the intrauterine pregnancy.
Nabothian cysts appear most often as firm bumps on the cervix's surface. A woman may notice the cyst when inserting a diaphragm or cervical cap, or when checking the cervix as part of fertility awareness. A health care provider may notice the cysts during a pelvic exam.