​Kembara Xtra - Medicine - Cervical Cancer

​Kembara Xtra - Medicine - Cervical Cancer 
Introduction The majority of cervical cancers start in the transformation zone, with 60-75% of cases coming from squamous epithelium and 25–40% from glandular tissue. Cervical cancer is a malignant tumor that arises from the uterine cervix.

Incidence and prevalence in Epidemiology 

Incidence
Eighty-four percent of cervical cancer cases are from resource-limited regions, making it the fourth most common cancer in women worldwide and the most common gynecologic cancer. Cervical cancer has a bimodal distribution, with the highest risk among women between the ages of 40 and 59 and over 70.
However, there has been a rise in incidence in women between the ages of 30 and 35 in recent years.
Prevalence
According to the American Cancer Society (ACS), there will be 4,170 fatalities and 13,240 new cases of invasive cancer in the United States in 2018. In this country, Hispanic women are most at risk, followed by African Americans, Asians, and whites.
Native Alaskans and American Indians have the lowest risk, which may be related to poor screening rates.


Pathophysiology and Etiology 
The most significant etiologic factor is high-risk (HR) serotype human papillomavirus infection.
Nearly 80 million Americans and 14 million additional people worldwide have HPV infection, which has a high prevalence.
Seventy percent of cervical cancers are caused by HR serotypes 16 and 18, and ongoing HR-HPV infection encourages cell cycle coding mistakes that lead to dysplastic alterations in the endocervical cellular lining. Additionally, HPV promotes the tumor-suppressor genes p53 and Rb through activating the oncogenic proteins E6 and E7.
Tumor growth occurs by hematogenous and lymphatic spread (Halstedian growth).

Genetics
Based on their related risk of cervical cancer, HPV types can be broadly divided into the following groups:
HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68 are considered high risk.
6, 11, 40, 42, 43, 44, 53, 54, 61, 72, 73, and 81 are considered low risk.

Cervical cancer risk factors include persistent HPV infection, early coitarche, multiple sexual partners, unprotected sex, a history of STIs, low socioeconomic status, obesity (increases the risk for adenocarcinoma type), non-white race, first birth before the age of 20, high parity (>3 foetuses), lack of or decreased access to health care, and difficulty getting regular Pap tests.

Prevention 
The cornerstone of prevention comprises both immunization against HR-HPV in addition to routine screening with a Pap test (or HPV test). Education about tobacco cessation and healthy sexual behaviors is also crucial.
The HPV vaccines protect against the wart-causing serotypes (6 and 11) as well as the HPV serotypes (16 and 18), which are most frequently linked to the development of cervical cancer.
The three vaccines that the FDA has approved are two-serotype Cervarix (HPV 16 and 18), four-serotype Gardasil 4, and nine-serotype Gardasil 9.
It is advised that everyone up to the age of 26 get vaccinated.
– 11 or 12 year old males and girls in two doses spaced six to twelve months apart. It can also be administered to children as young as nine.
- Children under the age of 15 years old should receive 3 doses spaced 6 months apart.
- People with immune compromise aged 9 to 26; men who have sex with males; and LGBTQ people
Regular screening with a Pap test (or an HPV test) is crucial for spotting early-stage illness and its antecedents. Up to 80% of cervical cancer cases might be avoided via screening worldwide.
The Society of Gynecologic Oncology (SGO), American College of Obstetricians and Gynecologists (ACOG), and the American Society for Colposcopy and Cervical Pathology (ASCCP) have all accepted the U.S. Preventive Services Task Force's (USPSTF) most recent screening recommendations.
- Cytology alone every three years for females 21 to 29 years old.
 Women between the ages of 30 and 65 should have cytology testing alone every three years, HR-HPV testing alone every five years (using an assay specifically approved by the FDA for HPV-screening-only testing), or cytology plus HR-HPV every five years.
The International Federation of Gynecology and Obstetrics (FIGO) recommends visual inspection with acetic acid (VIA) or Lugol iodine (VILI) as alternatives to Pap smears in resource-poor settings. An alternative screening algorithm using a risk-based strategy and specific FDA-approved high-risk HPV tests followed by cytology for positive screens is advised. Cervical cancer screening is still the primary preventive measure for both vaccinated and unvaccinated women, notwithstanding HPV vaccination.


Preinvasive or invasive lesions of the vulva, vagina, oral, anal, and oropharyngeal malignancies are associated with condyloma acuminata.


Patients with HPV infection may not exhibit any symptoms. Through cervical cancer screening, early stages can accidentally be found.
● Postcoital vaginal bleeding and irregular or excessive bleeding are the most frequent signs of cervical cancer. Vaginal discharge is one of the additional signs.

Less frequent symptoms include urinary problems, lower extremity edema, vesicovaginal and rectovaginal fistula, and low back pain radiating down the posterior leg.

clinical assessment 

It is crucial to perform a thorough pelvic exam because: - Many patients have a normal exam, particularly with microinvasive illness; and - Exophytic, endophytic, polypoid, papillary, ulcerative, or necrotic lesions might occur.
– may have a discharge that is bloody, purulent, or watery.
Enlarged supraclavicular or inguinal lymphadenopathy, lower extremity edema, ascites, or decreased breath sounds with lung auscultation may indicate metastases or advanced stage disease. Bimanual and rectovaginal examination should be carried out in women with symptoms of cervical cancer to evaluate uterine size, vaginal wall, rectovaginal septum, and parametrial, uterosacral, and pelvic sidewall involvement.

Differential diagnoses include endometrial cancer metastases or gestational trophoblastic neoplasia, as well as significant cervicitis and erosion, glandular hyperplasia, sexually transmitted infections, and cervical condyloma, leiomyoma, or polyps.


Diagnostic tests and laboratory results 

Initial examinations (lab, imaging)
The only reliable method of diagnosis is colposcopy with guided biopsies and/or biopsy of gross lesions.
The CBC may reveal anemia.
Hematuria may be seen on a urine test.
BUN, creatinine, and liver function tests (LFTs) may be useful in advanced disease.
A positron emission tomography (PET) scan or a CT scan of the chest, abdomen, and pelvis for the assessment of metastatic disease
Imaging does not change the tumor stage, with the exception of intravenous pyelograms (IVP) and chest x-rays (CXR).
MRI of the abdomen may be useful for planning radiation therapy or assessing parametrial involvement in individuals who are surgical candidates.

Tests in the Future & Special Considerations
Exams performed under anesthesia may be useful in identifying the clinical stage, severity of the disease, and surgical eligibility.
Cervical conization and endocervical curettage, where necessary, to assess the extent of the invasion and the presence of lymphovascular involvement.
Proctoscopy for invasion into the rectum and cystoscopy to assess bladder invasion

Interpretation of Tests

The majority of cases of invasive squamous cell cancer are ectocervical in origin.
The glandular cells that produce endocervical mucus give rise to adenocarcinomas. Exams frequently reveal a "bulky," "barrelshaped" cervix.
Rare mixed cell types, neuroendocrine tumors, sarcomas, lymphomas, and melanomas are examples of other cell types.

General Management of Treatment 

Enhance nutritional status, cure pelvic infections, and treat anemia (Hb 12 g/dL).
Lymph node assessment is essential for staging and treatment.
Prior to starting chemoradiation, urinary tract blockage must be corrected.
Prior to chemotherapy, a PET/CT scan should be used to assess the lymph nodes for involvement.

Medication 

Chemoradiation combined with a treatment containing cisplatin improves survival compared to pelvic and extended-field radiation alone.
Neoadjuvant treatment might prolong survival in patients with early-stage and locally progressed malignancies, but additional research is required.
The addition of the antiangiogenesis drug bevacizumab to standard combination chemotherapy (cisplatin/topotecan or cisplatin/paclitaxel) for recurrent, persistent, or metastatic disease has been shown to improve overall survival. Adjuvant chemotherapy after chemoradiation may improve progression-free survival in patients who receive primary chemoradiation for stages IIB to IVA tumors.

Initial Line
For stages IB2 to IVA, chemotherapy is the preferred treatment.
The recommended treatment plan consists of weekly radiation therapy plus cisplatin, or carboplatin (if cisplatin intolerance exists).
Cisplatin/paclitaxel/bevacizumab is the standard first-line therapy for recurrent or metastatic illness.

Next Line

Fluorouracil and cisplatin are included in the other suggested regimen.


Motives for the Referral 
patient multidisciplinary management where necessary and promptly

Further Treatments 

Chemoradiation (without surgery) is the first-line treatment for most bulky stage IB2 cancers as well as tumors stage IIB and higher (gross lesions with apparent parametrial involvement).
External beam pelvic radiation combined with brachytherapy is frequently used.
Extended-field radiation or lymph node surgery may be used before radiation therapy if para-aortic lymph node metastases are suspected.

Procedures involving surgery Patients with early-stage tumors have the option of surgical therapy.
Cryotherapy, laser ablation, cold knife conization, or the loop electrosurgical excision procedure (LEEP) can be used to remove precursor lesions (cervical intraepithelial neoplasia [CIN]) Stage IA1 (lesions with less than 3-mm invasion from the basement membrane) without lymphovascular space invasion can be treated with conization or a straightforward extrafascial hysterectomy
Stage IA2 (lesions with >3 mm but 5 mm invasion from basement membrane): depending on the clinical situation, radiotherapy or radical hysterectomy with lymph node dissection are options. In terms of intraoperative blood loss, length of hospital stay, and intraoperative and postoperative complications, robotic radical hysterectomy (RRH) has proven to be superior to laparoscopic radical hysterectomy and open radical hysterectomy. RRH can be regarded as a safe and effective therapeutic procedure for the management of cervical cancer.
Stages IA2 to IB1: In some cases, radical trachelectomy to preserve fertility may be an option.
Stages IB1 to IIA (gross lesions without evident parametrial involvement): Depending on the clinical situation, options include primary chemoradiation with brachytherapy and teletherapy or radical hysterectomy with lymph node biopsy. There is no discernible difference in survival at 5 years between women who got radiation treatment and those who received no additional treatment at stage IB when comparing adjuvant radiotherapy with no adjuvant radiotherapy (risk ratio [RR] = 0.8, 95% confidence interval 0.3-2.4). The probability of disease progression at 5 years, however, was considerably lower for women who received radiation (RR 0.6, 95% CI 0.4-0.9).

Primary pelvic exenteration may be possible in Stage IVA (lesions limited to central metastasis to the bladder and/or rectum).
Stage IVB (lesions that have spread to distant organs): Palliation is the goal of treatment; as a result, palliative care should be referred as soon as possible.

pregnant women's issues

The gestational age, the stage of the lesion, and the mother's appraisal of the risks and advantages of the proposed course of treatment all influence management.

The best course of action for abnormal cytology is colposcopy with targeted biopsies.
Prior to 16 weeks of pregnancy, cervical cancer in pregnant women should be identified and treated as away.
Early stages (IA1, IA2, IB) of pregnancy diagnosed after 16 weeks of gestation may be treated later to allow for fetal maturation.
Treatment may be determined by the gestational age at the time of diagnosis for pregnant women with advanced disease (stage IB2) identified after 16 weeks. Trachelectomy or conization for microinvasive cancer. Follow up at the 6-week postpartum visit if the depth of the invasion is less than 3 mm.

The timing of decisive therapy for invasive carcinoma depends on the mother's preferences, the disease's stage, and the gestational age at the time of diagnosis.

Those behind admission 
Active bleeding signs and urinary symptoms
Active vaginal bleeding can be managed with prompt radiation therapy and vaginal packing. Dehydration. Complications following surgery, chemotherapy, or radiation.
Recognition of ureteral obstruction, hydronephrosis, and urosepsis as well as prompt management are required. Multidisciplinary assessment-based discharge guidelines are also required.


Patient Follow-Up Monitoring

 Following the conclusion of definitive therapy and according to each patient's risk factors, patients are assessed through physical and pelvic examinations:
Every 3 to 6 months for two years, every 6 to 12 months for the next five years, and then annually after that
CT and PET scans are helpful in discovering metastases when recurrence is suspected. Pap smears may be performed annually but have a limited sensitivity for detecting recurrence. Preferably 3 to 4 months after therapy Vaginal hemorrhage, unexplained weight loss, leg edema, and pelvic or thigh pain are symptoms of recurrence.


Prognosis Invasive cervical carcinoma can be successfully treated if found early.
The expected 5-year survival percentage for early-stage (stage 1A, where the cancer has just slightly progressed inside the cervix) cases is 92%.
Stage IB has an 80% 5-year survival rate, stage IIA 63%, stage IIB 58%, stage III 30%, and stage IVA 16% according to the 2012 ACS.
It is possible to predict the clinical response to neoadjuvant chemotherapy and the presence of residual disease using raised squamous cell carcinoma antigen (SCC-Ag) serum levels assessed by the ELISA technique. A considerably greater frequency of treatment failure was seen 2 to 3 months after RT in patients with persistently elevated SCC-Ag levels. Serum SCC-Ag levels are also beneficial for tracking the effectiveness of treatment, the development of the illness, recurrence, and the unfavorable prognosis of SCCs. A clinical pelvic examination in conjunction with SCC-Ag levels can help determine whether additional treatment is necessary.


Complications include: Hemorrhage; Pelvic infection; Genitourinary fistula; Bladder dysfunction; Sexual dysfunction; Ureteral blockage with renal failure; Loss of ovarian function from radiotherapy or reason for bilateral oophorectomy
Lower extremity lymphedema, pulmonary embolism, and gastrointestinal obstruction