Bereks

• Vaccines


  Help decrease the incidence of cervical cancer
• The most common histologic type of cervical cancer is squamous, and the relative and absolute incidence of adenocarcinoma is increasing. Both histologies are caused by HPV infection.
• Cervical cancer staging


  • Clinically staged, although modern radiographic modalities such as computed tomography, magnetic resonance imaging, ultrasound, or positron emission tomography, if available, may be beneficial for individual treatment planning
  • Staging system has been updated in 2018
• Treatment of cervical cancer

  1. Early-stage disease (stages I to IIA) can be treated with either radical surgery or radiation therapy

  2. Advanced stage disease (stages IIB to IV) is best treated with chemoradiation, including brachytherapy
• Vaginal cancer


  • A rare disease with many similarities to cervical cancer
  • Radiation therapy is the mainstay of treatment for most patients, however, select patients may be treated with radical surgery
• Minimally invasive radical hysterectomy

  • Laparoscopic and robotic radical hysterectomies were being performed with larger degree of frequency in highly selected patients world wide
• Cervical cancer ranks as the third most common gynecologic neoplasm in the United States, behind cancer of the uterine corpus and ovary, mainly as a result of the effectiveness of screening programs
• Worldwide, cervical carcinoma continues to be a significant health care problem. In developing countries, where health care resources are limited, cervical carcinoma is the second most frequent cause of cancer death in women
• Cervical cancer is preventable, it is imperative that gynecologists and other primary health care providers for women be familiar with vaccination programs, screening techniques, diagnostic procedures, and risk factors for cervical cancer and management of preinvasive disease
• Vaginal cancer is a rare tumor that shares an epidemiology and risk factor profile that is similar to cervical cancer
• Invasive cancer of the cervix is considered a preventable disease because it has a long preinvasive state, cervical cytology screening programs are available, and the treatment of preinvasive lesions is effective
• In spite of the preventable nature of this disease, the CDC reported 12,578 new cases of invasive cervical cancer resulting in 4,115 deaths in the United States in 2014
• Nationally, the lifetime probability of developing cervical cancer is 1:128
• It is estimated that 30% of cervical cancer cases will occur in women who have never had a Papanicolaou (Pap) test. In developing countries, this percentage approaches 60%
• The mean age for cervical cancer in the United States is 47 years, and the distribution of cases is bimodal, with peaks at 35 to 39 years and 60 to 64 years of age
• Risk factors for cervical cancer

  • Young age at first intercourse (younger than 16 years)
  • Multiple sexual partners
  • Cigarette smoking
  • Race
  • High parity
  • Low socioeconomic status
  • Chronic immune suppression
• The relationship to oral contraceptive use was debated. Some investigators proposed that use of oral contraceptives might increase the incidence of cervical glandular abnormalities; however, this hypothesis was not consistently supported
• The initiating event in cervical dysplasia and carcinogenesis is infection with HPV. HPV infection was detected in up to 99% of women with squamous cervical carcinoma
• HPV is the causative agent in both squamous and adenocarcinoma of the cervix, but the respective tumors may have different carcinogenic pathways
• High-risk HPV subtypes


  • 16
  • 18
• Mechanism by which HPV affects cellular growth and differentiation

  Through the interaction of viral E6 and E7 proteins with tumor suppressor genes p53 and Rb, respectively
• Initially, there were two HPV vaccines, the quadrivalent Gardasil and the bivalent Cervarix, approved by the U.S. Food and Drug Administration (FDA). Both protect against HPV subtypes 16 and 18
• Efficacy of Gardasil


  • 97% to 100% for preventing cervical intraepithelial neoplasia (CIN) grades 2 and 3 caused by HPV 16 or 18 in females who were not previously infected with either HPV 16 or 18 before vaccination
  • Only 44% in those who were infected prior to vaccination
• Recently, the FDA has approved a third HPV vaccine, Gardasil-9, which protects against the four subtypes of the quadrivalent vaccine plus an additional five high-risk subtypes (HPV 31/33/45/52/58)
• Efficacy of the 9-valent vaccine


  97% in the HPV-naïve patient population for preventing CIN 2,3, VIN 2 or 3, and VAIN 2 or 3
• The FDA also extended the recommended age indication for Gardisil-9 to include men and women ages 9 to 45
• Because these vaccines do not protect against all HPV subtypes, vaccinated women need to continue to receive cervical cancer screening according to published guidelines
• Vaginal bleeding


  The most common symptom occurring in patients with cancer of the cervix
• The false-negative rate for Pap tests in the presence of invasive cancer is up to 50%, so a negative Pap test should never be relied on in a symptomatic patient
• Initial evaluation of suspected cervical cancer


  1. General physical examination to include evaluation of the supraclavicular, axillary, and inguinofemoral lymph nodes

  2. Pelvic examination with speculum insertion and cervix inspection

  3. Rectal examination to help establish cervical consistency and size
• Diagnosis of cervical cancer

  1. If obvious tumor growth is present, a cervical biopsy is usually sufficient

  2. If gross disease is not present, a colposcopic examination with cervical biopsies and endocervical curettage is warranted

  3. If the diagnosis cannot be established conclusively with colposcopy and directed biopsies, cervical conization may be necessary
• Colposcopic findings suggesting invasion

  • Abnormal blood vessels
  • Irregular surface contour with loss of surface epithelium
  • Color tone change
• Colposcopically directed biopsies may permit the diagnosis of frank invasion and thus avoid the need for diagnostic cone biopsy, allowing treatment to be administered without delay
• Abnormal blood vessels


  Looped, branched, or reticular vessels that arise from the cervical stroma and are pushed to the surface as the underlying cancer invades
• Abnormal reticular vessels


  Represent the terminal capillaries of the cervical epithelium that are exposed when the surface epithelium is eroded by cancer
• Irregular surface contour


  Occurs as a result of tumor growth causing ulceration and loss of surface epithelium, or papillary characteristics of the lesion
• Color tone change


  Yellow-orange rather than the expected pink of intact squamous epithelium or the red of the endocervical epithelium, due to increasing vascularity, surface epithelial necrosis, and in some cases, production of keratin
• Adenocarcinoma of the cervix does not have a specific colposcopic appearance. All of the aforementioned blood vessels may be seen in these lesions
• Histologic assessment of invasion

  1. Cervical conization is required to assess correctly the depth and the linear extent of involvement when microinvasion is suspected

  2. Early invasion is characterized by a protrusion of malignant cells from the stromal-epithelial junction

  3. Lesions that are less than 3 mm in depth are classified as FIGO stage IA1

  4. Lesions that are 3 to 5 mm or more in depth and up to 7 mm in linear extent are classified as FIGO stage IA2
• Lesions that have invaded 3 mm or less rarely metastasize, patients in whom lesions invade between 3 and 5 mm have positive pelvic lymph nodes in 3% to 8% of cases