Made by DATEXIS (Data Science and Text-based Information Systems) at Beuth University of Applied Sciences Berlin
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)
Funded by The Federal Ministry for Economic Affairs and Energy; Grant: 01MD19013D, Smart-MD Project, Digital Technologies
There is currently no specific treatment for HPV infection. However, the viral infection, more often than not, clears to undetectable levels by itself. According to the Centers for Disease Control and Prevention, the body's immune system clears HPV naturally within two years for 90% of cases (see Clearance subsection in Virology for more detail). However, experts do not agree on whether the virus is completely eliminated or reduced to undetectable levels, and it is difficult to know when it is contagious.
Follow up care is usually recommended and practiced by many health clinics. Follow-up is sometimes not successful because a portion of those treated do not return to be evaluated. In addition to the normal methods of phone calls and mail, text messaging and email can improve the number of people who return for care.
The HPV vaccines can prevent the most common types of infection. To be effective they must be used before an infection occurs and are therefore recommended between the ages of nine and thirteen. Cervical cancer screening, such as with the Papanicolaou test (pap) or looking at the cervix after using acetic acid, can detect early cancer or abnormal cells that may develop into cancer. This allows for early treatment which results in better outcomes. Screening has reduced both the number and deaths from cervical cancer in the developed world. Warts can be removed by freezing.
Methods of reducing the chances of infection include sexual abstinence, condoms, vaccination, and microbicides.
Physically ablative methods are more likely to be effective on keratinized warts. They are also most appropriate for patients with fewer numbers of relatively smaller warts.
- Simple excision, such as with scissors under local anesthesia, is highly effective.
- Liquid nitrogen cryosurgery is usually performed in an office visit, at weekly intervals. It is effective, inexpensive, safe for pregnancy, and does not usually cause scarring.
- Electrocauterization (sometimes called "loop electrical excision procedure" or LEEP) is procedure with a longer history of use, and is considered effective.
- Laser ablation has less evidence to suggest its use. It may be less effective than other ablative methods. It is extremely expensive, and often used as a last resort.
- Formal surgical procedures, performed by a specialist under general anesthesia, may be necessary for larger or more extensive warts, intra-anal warts, or warts in children. It carries a greater risk of scarring than other methods.
Podophyllin, podofilox and isotretinoin should not be used during pregnancy, as they could cause birth defects in the fetus.
The goals of care are to optimise survival and locoregional disease control, and prevent spread to distant areas of the body (metastasis), while minimising short and long term morbidity. There is no high quality Level I evidence from prospective clinical trials in HPV+OPC, therefore treatment guidelines must rely on data from treatment of OPC in general and from some retrospective unplanned subsetting of those studies, together with data for head and neck cancer in general. Treatment for OPC has traditionally relied on radiotherapy, chemotherapy and/or other systemic treatments, and surgical resection. Depending on stage and other factors treatment may include a combination of modalities. The mainstay has been radiotherapy in most cases. a pooled analysis of published studies suggested comparable disease control between radiation and surgery, but higher complication rates for surgery +/- radiation. Ideally a single modality approach is preferred, since triple modality is associated with much more toxicity, and a multidisciplinary team in a large centre with high patient volumes is recommended.
Differences in response to treatment between HPV-OPC and HPV+OPC may include differences in the extent and manner in which cellular growth-regulatory pathways are altered in the two forms of OPC. For instance in HPV+OPC the HPV E6 and E7 oncogenes merely render the p53 and pRb pathways dormant, leaving open the possibility of reactivation of these pathways by down-regulating (reducing) expression of the oncogenes. This is in contrast to the mutant form of p53 found in HPV-OPC that is associated with treatment resistance. Furthermore, it is suggested that the effects of E6 and E7 on these pathways renders the tumour more radiosensitive, possibly by interference with mechanisms such as DNA repair, repopulation signalling, and cell-cycle redistribution. The microenvironment is also important, with radiation increasing host immune response to viral antigens expressed on the tumour. Also, there is an association between an increase in tumour-infiltrating lymphocytes and in circulating white blood cells in HPV+OPC patients and better prognosis. This implies a role for an adaptive immune system in suppressing tumour progression.
Data on the use of postoperative radiation therapy (PORT) is largely confined to historical or retrospective studies rather than high quality randomized clinical trials and are based on the overall population of patients with head and neck cancer, rather than specific studies of HPV+OPC, which would have formed a very small proportion of the population studied. Despite surgical excision, in the more advanced cases local and regional recurrence of the cancer, together with spread outside of the head and neck region (metastases) are frequent. The risk of subsequent recurrent disease is highest in those tumours where the pathology shows tumour at the margins of the resection (positive margins), multiple involved regional lymph nodes and extension of the tumour outside of the capsule of the lymph node (extracapsular extension). PORT was introduced in the 1950s in an attempt to reduce treatment failure from surgery alone. Although never tested in a controlled setting, PORT has been widely adopted for this purpose. In an analysis of surgical treatment failure at Memorial Sloan-Kettering Cancer Center, patients treated with surgery alone between 1960–1970 had failure rates of 39 and 73% for those with negative and positive surgical margins respectively. These were compared to those who received PORT (with or without chemotherapy) from 1975–1980. The latter group had lower failure rates of 2% and 11% respectively. In addition, one randomised study from the 1970s (RTOG 73-03) compared preoperative radiation to PORT, and found lower failure rates with the latter.
The addition of another modality of treatment is referred to as adjuvant (literally helping) therapy, compared to its use as the initial (primary) therapy, also referred to as radical therapy. Consequently, many of these patients have been treated with adjuvant radiation, with or without chemotherapy. In the above series of reports of minimally invasive surgery, many (30–80%) patients received adjuvant radiation. However, functional outcomes were worse if radiation was added to surgery and worst if both radiation and chemotherapy were used. Radiation dosage has largely followed that derived for all head and neck cancers, in this setting, based on risk. Historically only one randomised clinical trial has addressed optimal dosage, allocated patients to two dosage levels, stratified by risk, but showed no difference in cancer control between the low and high doses (63 and 68.4 Gy), but a higher incidence of complications at the higher doses. Consequently, the lower dose of 57.6 Gy was recommended. Because the authors used a fractionation scheme of 1.8 Gy per treatment, this dosage was not widely adopted, practitioners preferring a larger fraction of 2 Gy to produce a shorter treatment time, and a slightly higher dose of 60 Gy in 2 Gy fractions (30 daily treatments). Yet 57.6 Gy in 1.8 Gy fractions is equivalent (iso-effective dose) to only 56 Gy in 2 Gy fractions. 60 Gy corresponds to the 63 Gy used as the low dose in the high risk group. 60 Gy was also the dose used in RTOG 73-03. Subsequently, there was a tendency to intensify treatment in head and neck cancer, and a number of centres adopted a dose of 66 Gy, at least for those patients with adverse tumour features. The effectiveness of PORT in HPV+OPC receives some support from a cohort study (Level 2b), although the number of patients was low, and the number of events (recurrent disease or death) only 7%. Another retrospective population-level study (Level 4) of the SEER database (1998–2011) concluded that there was an overall survival but not disease-specific survival effect of radiation in 410 patients with a single lymph node involved, but used only univariate statistical analysis and contained no information on HPV status. A subsequent much larger study on a similar population in the National Cancer Database (2004–2013) of over 9,000 patients found a survival advantage but this was only in HPV-OPC, not in 410 HPV+OPC patients.
While most cases require no treatment, therapy options include cryotherapy, application of a topical salicylic acid compound, surgical and laser ablation.
There are several treatment options for penile cancer, depending on staging. They include surgery, radiation therapy, chemotherapy, and biological therapy. The most common treatment is one of five types of surgery:
- Wide local excision—the tumor and some surrounding healthy tissue are removed
- Microsurgery—surgery performed with a microscope is used to remove the tumor and as little healthy tissue as possible
- Laser surgery—laser light is used to burn or cut away cancerous cells
- Circumcision—cancerous foreskin is removed
- Amputation (penectomy)—a partial or total removal of the penis, and possibly the associated lymph nodes.
Radiation therapy is usually used adjuvantly with surgery to reduce the risk of recurrence. With earlier stages of penile cancer, a combination of topical chemotherapy and less invasive surgery may be used. More advanced stages of penile cancer usually require a combination of surgery, radiation and chemotherapy.
In addition to all the above, treatment of the underlying disease like brucellosis, is important to limit disease recurrence.
Staging and treatment are generally handled by an oncologist familiar with gynecologic cancer. Surgery is a mainstay of therapy depending on anatomical staging and is usually reserved for cancers that have not spread beyond the vulva. Surgery may involve a wide local excision, radical partial vulvectomy, or radical complete vulvectomy with removal of vulvar tissue, inguinal and femoral lymph nodes. In cases of early vulvar cancer, the surgery may be less extensive and consist of wide excision or a simple vulvectomy. Surgery is significantly more extensive when the cancer has spread to nearby organs such as the urethra, vagina, or rectum. Complications of surgery include wound infection, sexual dysfunction, edema and thrombosis, as well as lymphedema secondary to dissected lymph nodes.
Sentinel lymph node (SLN) dissection is the identification of the main lymph node(s) draining the tumor, with the aim of removing as few nodes as possible, decreasing the risk of adverse effects. Location of the sentinel node(s) may require the use of technetium(99m)-labeled nano-colloid, or a combination of technetium and 1% isosulfan blue dye, wherein the combination may reduce the number of women with "'missed"' groin node metastases compared with technetium only.
Radiation therapy may be used in more advanced vulvar cancer cases when disease has spread to the lymph nodes and/or pelvis. It may be performed before or after surgery. Chemotherapy is not usually used as primary treatment but may be used in advanced cases with spread to the bones, liver or lungs. It may also be given at a lower dose together with radiation therapy.
Women with vulvar cancer should have routine follow-up and exams with their oncologist, often every 3 months for the first 2–3 years after treatment. They should not have routine surveillance imaging to monitor the cancer unless new symptoms appear or tumor markers begin rising. Imaging without these indications is discouraged because it is unlikely to detect a recurrence or improve survival and is associated with its own side effects and financial costs.
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.
Chemotherapy in throat cancer is not generally used to "cure" the cancer as such. Instead, it is used to provide an inhospitable environment for metastases so that they will not establish in other parts of the body. Typical chemotherapy agents are a combination of paclitaxel and carboplatin. Cetuximab is also used in the treatment of throat cancer.
Docetaxel-based chemotherapy has shown a very good response in locally advanced head and neck cancer. Docetaxel is the only taxane approved by US FDA for head and neck cancer, in combination with cisplatin and fluorouracil for the induction treatment of inoperable, locally advanced squamous cell carcinoma of the head and neck.
While not specifically a chemotherapy, amifostine is often administered intravenously by a chemotherapy clinic prior to IMRT radiotherapy sessions. Amifostine protects the gums and salivary glands from the effects of radiation.
Induction chemotherapy is the treatment adapted for shrinking the tonsil tumor. It is given prior to other treatments, hence, the term induction. After the therapy is completed, the patient is asked to rest and is evaluated over a period of time. Then the patient is given chemo-radiation therapy (a combination of chemotherapy and radiation) to completely destroy the tumor cells.
Photodynamic therapy may have promise in treating mucosal dysplasia and small head and neck tumors. Amphinex is giving good results in early clinical trials for treatment of advanced head and neck cancer.
As of 2014 there was no cure for laryngeal papillomatosis, and treatment options aimed to remove and limit the recurrence of the papillomas. Repeated treatments are often needed because of the recurrent nature of the virus, especially for children, as the juvenile form of laryngeal papillomatosis often triggers more aggressive relapses than the adult form. Between recurrences, voice therapy may be used to restore or maintain the persons's voice function.
Surgical excision (removal) of the tumor is usually recommended if the tumor is small enough, and if surgery is likely to result in a functionally satisfactory result. Radiation therapy with or without chemotherapy is often used in conjunction with surgery, or as the definitive radical treatment, especially if the tumour is inoperable. Surgeries for oral cancers include:
- Maxillectomy (can be done with or without orbital exenteration)
- Mandibulectomy (removal of the mandible or lower jaw or part of it)
- Glossectomy (tongue removal, can be total, hemi or partial). When glossectomy is performed for smaller tumors (< 4 cm), the adequacy of resection (margin status) is best assessed from the resected specimen itself. The status of the margin (positive/tumor cut through versus negative/clear margin) obtained from the glossectomy specimen appears to be of prognostic value, while the status of the margin sampled from the post-glossectomy defect is not. The method of margin sampling appears to correlate with local recurrence: preference for tumor bed/defect margins may be associated with worse local control.
- Radical neck dissection
- Mohs surgery or CCPDMA
- Combinational, e.g. glossectomy and laryngectomy done together
- Feeding tube to sustain nutrition
Owing to the vital nature of the structures in the head and neck area, surgery for larger cancers is technically demanding. Reconstructive surgery may be required to give an acceptable cosmetic and functional result. Bone grafts and surgical flaps such as the radial forearm flap are used to help rebuild the structures removed during excision of the cancer. An oral prosthesis may also be required. Most oral cancer patients depend on a feeding tube for their hydration and nutrition. Some will also get a port for the chemo to be delivered. Many oral cancer patients are disfigured and suffer from many long term after effects. The after effects often include fatigue, speech problems, trouble maintaining weight, thyroid issues, swallowing difficulties, inability to swallow, memory loss, weakness, dizziness, high frequency hearing loss and sinus damage.
Survival rates for oral cancer depend on the precise site and the stage of the cancer at diagnosis. Overall, 2011 data from the SEER database shows that survival is around 57% at five years when all stages of initial diagnosis, all genders, all ethnicities, all age groups, and all treatment modalities are considered. Survival rates for stage 1 cancers are approximately 90%, hence the emphasis on early detection to increase survival outcome for patients. Similar survival rates are reported from other countries such as Germany.
Following treatment, rehabilitation may be necessary to improve movement, chewing, swallowing, and speech. Speech and language pathologists may be involved at this stage.
Chemotherapy is useful in oral cancers when used in combination with other treatment modalities such as radiation therapy. It is not used alone as a monotherapy. When a cure is unlikely, it can also be used to extend life and can be considered palliative but not curative care. Biological agents such as Cetuximab have recently been shown to be effective in the treatment of squamous cell head and neck cancers, and are likely to have an increasing role in the future management of this condition when used in conjunction with other established treatment modalities.
Treatment of oral cancer will usually be by a multidisciplinary team, with treatment professionals from the realms of radiation, surgery, chemotherapy, nutrition, dentistry, and even psychology all possibly involved with diagnosis, treatment, rehabilitation, and patient care.
Early radio-sensitive tumors are treated by radiotherapy along with irradiation of cervical nodes. The radiation uses high-energy X-rays, electron beams, or radioactive isotopes to destroy cancer cells.
The treatment of cervical cancer varies worldwide, largely due to access to surgeons skilled in radical pelvic surgery, and the emergence of fertility-sparing therapy in developed nations. Because cervical cancers are radiosensitive, radiation may be used in all stages where surgical options do not exist. Surgical intervention may have better outcomes than radiological approaches. In addition, chemotherapy can be used to treat cervical cancer, and has been found to be more effective than radiation alone.
Microinvasive cancer (stage IA) may be treated by hysterectomy (removal of the whole uterus including part of the vagina). For stage IA2, the lymph nodes are removed, as well. Alternatives include local surgical procedures such as a loop electrical excision procedure or cone biopsy.
If a cone biopsy does not produce clear margins (findings on biopsy showing that the tumor is surrounded by cancer free tissue, suggesting all of the tumor is removed), one more possible treatment option for women who want to preserve their fertility is a trachelectomy. This attempts to surgically remove the cancer while preserving the ovaries and uterus, providing for a more conservative operation than a hysterectomy. It is a viable option for those in stage I cervical cancer which has not spread; however, it is not yet considered a standard of care, as few doctors are skilled in this procedure. Even the most experienced surgeon cannot promise that a trachelectomy can be performed until after surgical microscopic examination, as the extent of the spread of cancer is unknown. If the surgeon is not able to microscopically confirm clear margins of cervical tissue once the woman is under general anesthesia in the operating room, a hysterectomy may still be needed. This can only be done during the same operation if the woman has given prior consent. Due to the possible risk of cancer spread to the lymph nodes in stage 1b cancers and some stage 1a cancers, the surgeon may also need to remove some lymph nodes from around the uterus for pathologic evaluation.
A radical trachelectomy can be performed abdominally or vaginally and opinions are conflicting as to which is better. A radical abdominal trachelectomy with lymphadenectomy usually only requires a two- to three-day hospital stay, and most women recover very quickly (about six weeks). Complications are uncommon, although women who are able to conceive after surgery are susceptible to preterm labor and possible late miscarriage. A wait of at least one year is generally recommended before attempting to become pregnant after surgery. Recurrence in the residual cervix is very rare if the cancer has been cleared with the trachelectomy. Yet, women are recommended to practice vigilant prevention and follow-up care including Pap screenings/colposcopy, with biopsies of the remaining lower uterine segment as needed (every 3–4 months for at least 5 years) to monitor for any recurrence in addition to minimizing any new exposures to HPV through safe sex practices until one is actively trying to conceive.
Early stages (IB1 and IIA less than 4 cm) can be treated with radical hysterectomy with removal of the lymph nodes or radiation therapy. Radiation therapy is given as external beam radiotherapy to the pelvis and brachytherapy (internal radiation). Women treated with surgery who have high-risk features found on pathologic examination are given radiation therapy with or without chemotherapy to reduce the risk of relapse.
Larger early-stage tumors (IB2 and IIA more than 4 cm) may be treated with radiation therapy and cisplatin-based chemotherapy, hysterectomy (which then usually requires adjuvant radiation therapy), or cisplatin chemotherapy followed by hysterectomy. When cisplatin is present, it is thought to be the most active single agent in periodic diseases. Such addition of platinum-based chemotherapy to chemoradiation seems not only to improve survival but also reduces risk of recurrence in women with early stage cervical cancer (IA2-IIA).
Advanced-stage tumors (IIB-IVA) are treated with radiation therapy and cisplatin-based chemotherapy. On June 15, 2006, the US Food and Drug Administration approved the use of a combination of two chemotherapy drugs, hycamtin and cisplatin, for women with late-stage (IVB) cervical cancer treatment. Combination treatment has significant risk of neutropenia, anemia, and thrombocytopenia side effects.
For surgery to be curative, the entire cancer must be removed with no cancer found at the margins of the removed tissue on examination under a microscope. This procedure is known as exenteration.
Most conjunctival squamous cell carcinomas are removed with surgery. A few selected cases are treated with topical medication. Surgical excision with a free margin of healthy tissue is a frequent treatment modality. Radiotherapy, given as external beam radiotherapy or as brachytherapy (internal radiotherapy), can also be used to treat squamous cell carcinomas.
The first line of treatment is surgery to remove papillomas. Surgery does not prevent recurrences, and can lead to a number of serious complications. Laser technology, and carbon dioxide laser surgery in particular, has been used since the 1970s for the removal of papillomas; however, laser surgery is not without its risks, and has been associated with a higher occurrence of respiratory tract burns, stenosis, severe laryngeal scarring, and tracheoesophagyeal fistulae. Tracheotomies are offered for the most aggressive cases, where multiple debulking surgery failures have led to airways being compromised. The tracheotomies use breathing tubes to reroute air around the affected area, thereby restoring the person's breathing function. Although this intervention is usually temporary, some people must use the tube indefinitely. This method should be avoided if at all possible, since the breathing tube may serve as a conduit for spread of the disease as far down as the tracheobronchal tree.
A microdebrider is a tool that can suction tissue into a blade, which then cuts the tissue. Microdebriders are gradually replacing laser technology as the treatment of choice for laryngeal papillomatosis, due to their ability to selectively suction papillomas while relatively sparing unaffected tissue. In addition to the lower risk of complications, microdebrider surgery also is reportedly less expensive, less time-consuming, and more likely to give the person a better voice quality than the traditional laser surgery approaches.
Historically, the combination of external-beam radiation therapy (EBRT) has been the most common treatment for vaginal cancer. In early stages of vaginal cancer, surgery also has some benefit. This management and treatment is less effective for those with advanced stages of cancer but works well in early stages with high rates of cure. Advanced vaginal cancer only has a 5-year survival rates of 52.2%, 42.5% and 20.5% for patients with stage II, III and IVa disease. Newer treatments for advanced stages of ovarian have been developed. These utilize concurrent carboplatin plus paclitaxel, EBRT and high-dose-rate interstitial brachytherapy (HDR-ISBT).
When the chance of surgical removal of all cancerous tissue is very low or when the surgery has a chance of damaging the bladder, vagina or bowel, radiation therapy is used. When a tumor is less than 4 cm in diameter, radiation therapy provides excellent results. In these instances, the 5-year survival rate is greater than 80%. Treatments are individualized due to the rarity of vaginal cancer studies.
Most squamous cell carcinomas are removed with surgery. A few selected cases are treated with topical medication. Surgical excision with a free margin of healthy tissue is a frequent treatment modality. Radiotherapy, given as external beam radiotherapy or as brachytherapy (internal radiotherapy), can also be used to treat squamous cell carcinomas.
Mohs surgery is frequently utilized; considered the treatment of choice for squamous cell carcinoma of the skin, physicians have also utilized the method for the treatment of squamous cell carcinoma of the mouth, throat, and neck. An equivalent method of the CCPDMA standards can be utilized by a pathologist in the absence of a Mohs-trained physician. Radiation therapy is often used afterward in high risk cancer or patient types.
Electrodessication and curettage or EDC can be done on selected squamous cell carcinoma of the skin. In areas where SCC's are known to be non-aggressive, and where the patient is not immunosuppressed, EDC can be performed with good to adequate cure rate.
High-risk squamous cell carcinoma, as defined by those occurring around the eye, ear, or nose, is of large size, is poorly differentiated, and grows rapidly, requires more aggressive, multidisciplinary management.
Nodal spread:
1. Surgical block dissection if palpable nodes or in cases of Marjolin's ulcers but the benefit of prophylactic block lymph node dissection with Marjolin's ulcers is not proven.
2. Radiotherapy
3. Adjuvant therapy may be considered in those with high-risk SCC even in the absence of evidence for local mestastasis. Imiquimod (Aldara) has been used with success for squamous cell carcinoma "in situ" of the skin and the penis, but the morbidity and discomfort of the treatment is severe. An advantage is the cosmetic result: after treatment, the skin resembles normal skin without the usual scarring and morbidity associated with standard excision. Imiquimod is not FDA-approved for any squamous cell carcinoma.
In general, squamous cell carcinomas have a high risk of local recurrence, and up to 50% do recur. Frequent skin exams with a dermatologist is recommended after treatment.
There are many treatments and procedures associated with wart removal. A review of clinical trials of various cutaneous wart treatments concluded that topical treatments containing salicylic acid were more effective than placebo. Cryotherapy appears to be as effective as salicylic acid, but there have been fewer trials.
Vitamin A is associated with a lower risk as are vitamin B12, vitamin C, vitamin E, and beta-Carotene.
Nasopharyngeal carcinoma can be treated by surgery, by chemotherapy, or by radiotherapy. The expression of EBV latent proteins within undifferentiated nasopharyngeal carcinoma can be potentially exploited for immune-based therapies.
10 to 20% of patients treated for anal cancer will develop distant metastatic disease following treatment. Metastatic or recurrent anal cancer is difficult to treat, and usually requires chemotherapy. Radiation is also employed to palliate specific locations of disease that may be causing symptoms. Chemotherapy commonly used is similar to other squamous cell epithelial neoplasms, such as platinum analogues, anthracyclines such as doxorubicin, and antimetabolites such as 5-FU and capecitabine. JD Hainsworth developed a protocol that includes Taxol and Carboplatinum along with 5-FU. Median survival rates for patients with distant metastases ranges from 8 to 34 months.