A) Cervical Cancer Screening

• 1. Examination of Cervical Changes and Conditions
• 2. Pap Test
• 3. Human Papillomavirus (HPV)
• 4. Liquid based cytology

B) Endometrial cancer

• 1. Hysteroscopy & endometrial biopsy

C) Ovarian cancer

• 1. Ultrasound
• 2. Tumor markers
• 3. Doppler studies

D) Breast cancer

• 1. Yearly mammograms above 40 year age.
• 2. Clinical breast exam (CBE) about every 3 yearly (20-30 years), yearly for > 40 year age.
• 3. Breast self-exam (BSE) starting in their 20s.

I. CERVICAL CANCER

Cervical cancer is one of the deadliest cancer forms responsible for the growing ratio of women’s death every year. Cervical cancer is a malignantneoplasm arising from cells originating in the cervix uteri. One of the most common symptoms of cervical cancer is abnormal vaginal bleeding, but in some cases there may be no obvious symptoms until the cancer has progressed to an advanced stage. Treatment usually consists of surgery (including local excision) in early stages, and chemotherapy and/or radiotherapy in more advanced stages of the disease.

Cancer screening using the Pap smear can identify precancerous and potentially precancerous changes in cervical cells and tissue. Treatment of high-grade changes can prevent the development of cancer in many victims. Human papillomavirus (HPV) infection appears to be a necessary factor in the development of almost all cases (90 %) of cervical cancer. The cervix is the narrow portion of the uterus where it joins with the top of the vagina. Most cervical cancers are squamous cell carcinomas, Adenocarcinoma, is the second most common type. Very rarely, cancer can arise in other types of cells in the cervix

A) Causes :

Infection with some types of human papilloma virus (HPV) is the greatest risk factor for cervical cancer, followed by smoking. Other risk factors include human immunodeficiency virus (HIV). Not all of the causes of cervical cancer are known, however, and several other contributing factors have been implicated.

• a) Human papillomavirus -Human papillomavirus type 16 and 18 are the cause of 75% of cervical cancer globally while 31 and 45 are the cause of another 10%. Women who have many sexual partners have a greater risk. Use of condoms reduces, but does not always prevent transmission.
• b) Smoking- Smoking has also been linked to the development of cervical cancer. It is involved in etiology by direct and indirect methods. A direct way of contracting this cancer is a female smoker has a higher chance of CIN3 occurring which has the potential of forming cervical cancer. An indirect means it aids in development of HPV Infection.

B) Diagnosis :

• a) BiopsyWhile the Pap smear is an effective screening test, confirmation of the diagnosis of cervical cancer or pre-cancer requires a biopsy of the cervix. This is often done through colposcopy, a magnified visual inspection of the cervix. Medical devices used for biopsy of the cervix include punch forceps, Soft Biopsy or Soft-ECC. Further diagnostic and treatment procedures are loop electrical excision procedure (LEEP) and Conization, in which the inner lining of the cervix is removed to be examined pathologically. These are carried out if the biopsy confirms severe cervical intraepithelial neoplasia.
• b) Precancerous lesionsCervical intraepithelial neoplasia, the potential precursor to cervical cancer, is often diagnosed on examination of cervical biopsies by a pathologist. For premalignant dysplastic changes, the CIN (cervical intraepithelial neoplasia) grading is used

C) Cancer Subtypes :

Histologic subtypes of invasive cervical carcinoma include the following: Though squamous cell carcinoma is the cervical cancer with the most incidences, the incidence of adenocarcinoma of the cervix has been increasing in recent decades

• 1. Squamous cell carcinoma (about 80-85%)
• 2. Adenocarcinoma (about 15%)
• 3. Adenosquamous carcinoma
• 4. Small cell carcinoma
• 5. Neuroendocrine tumour
• 6. Glassy cell carcinoma
• 7. Villoglandular adenocarcinoma

Non-carcinoma malignancies which can rarely occur in the cervix include

• 1. Melanoma
• 2. lymphoma

D) Staging :

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 the following 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.

E) Prevention :

a) Screening :

• 1.Examination of Cervical Changes and Conditions –Direct visualization with or without staining under magnification to look for changes in the appearance because of recurrent infections. The appearance changes in the affected area. The change appears in the form of – change in colour, change in consistency, ulceration or overgrowth. Cervical examination s advised at least every 3 years after age of 30 years.
• 2. Pap test –The Papanicolaou test, for cervical cancer has been credited with dramatically reducing the number of cases of and mortality from cervical cancer in developed countries. Cervical cancer screening is typically recommended starting at age 21. Pap smear screening every 3–5 years with appropriate follow-up can reduce cervical cancer incidence by up to 80%.Abnormal results may suggest the presence of pre-cancerous changes allowing examination and possible preventive treatment. If precancerous disease or cervical cancer is detected early, it can be monitored or treated relatively noninvasively, with little impairment of fertility.
• 3. Human Papillomavirus (HPV) –HPV DNAdetection can be donefor the patients routinely as it’s one of leading etiology in cancer cervix. The kit is readily available at pathology labs and also with us.
• 4. Liquid based cytology –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. We support this screening every 5 years in those who are between 30 and 65 years when cytology is used in combination with HPV testing.

b) Vaccination :

There are two HPV vaccines (Gardasil and Cervarix) which reduce the risk of cancerous or precancerous changes of the cervix and perineum by about 93%. HPV vaccines are typically given to women age 9 to 26 as the vaccine is only effective if given before infection occurs. The vaccines have been shown to be effective for at least 4 to 6years, and it is believed they will be effective for longer.

c) Condoms :

Condoms are thought to offer some protection against cervical cancer. Evidence on whether condoms protect against HPV infection is mixed, but they may protect against genital warts and the precursors to cervical cancer. They also provide protection against other STDs, such as HIV and Chlamydia, which are associated with greater risks of developing cervical cancer.

d) Nutrition :

Vitamin A is associated with a lower risk as is vitamin B12, vitamin C, vitamin E, and beta-carotene, so including food rich in these vitamins is advised.

G) Treatment :

The treatment of cervical cancer varies worldwide, largely due to large variances in disease burden in developed and developing nations, 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.

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 (LEEP) or cone biopsy. For 1A1 disease, a cone biopsy (aka cervical conization) is considered curative. 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 patients 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; 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). Patients treated with surgery who have high risk features found on pathologic examination are given radiation therapy with or without chemotherapy in order 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. Advanced stage tumors (IIB-IVA) are treated with radiation therapy and cisplatin-based chemotherapy.

H) Prognosis :

Prognosis depends on the stage of the cancer. There is a high chance of a survival rate around 100 for women with microscopic forms of cervical cancer. With treatment, the 5-year relative survival rate for the earliest stage of invasive cervical cancer is 92%, and the overall (all stages combined) 5-year survival rate is about 72%.

According to the International Federation of Gynecology and Obstetrics, survival improves when radiotherapy is combined with cisplatin-based chemotherapy.

As the cancer metastasizes to other parts of the body, prognosis drops dramatically because treatment of local lesions is generally more effective than whole body treatments such as chemotherapy. Interval evaluation of the patient after therapy is imperative. Recurrent cervical cancer detected at its earliest stages might be successfully treated with surgery, radiation, chemotherapy, or a combination of the three. Thirty-five percent of patients with invasive cervical cancer have persistent or recurrent disease after treatment.

Regular screening has meant that pre-cancerous changes and early stage cervical cancers have been detected and treated early

II) ENDOMETRIAL CANCER

Uterine cancer or Endometrial cancer is another common type of cancer that hits the inner lining of the uterus, called endometrium. India, there are 0.88 million cancer cases with an incidence rate (ASR) of 105.5 per 100,000 in women. Uterine cancer most often occurs after or around the time when menopause begins. Women above 50 years and more are at a bigger risk of getting uterine cancer. Abnormal vaginal bleeding is the first big symptom of this form of cancer. Most often women mistake this abnormal bleeding with the onset of menopause, which can be dangerous. Women suffering from endometrial hyperplasia, high blood pressure and obesity are more likely to be victims of this kind of cancer. Females who started menstruating before the tender age of 12 and those afflicted with late menopause are more exposed to the threat of uterine cancer. However, the good news is that this kind of cancer is curable with surgery, radiation therapy and chemotherapy

A) Classification

• a) Carcinoma -Most endometrial cancers are carcinomas (usually adenocarcinomas), they originate from the single layer of epithelial cells that line the endometrium. They are broadly organized into two categories, type I and type II, based on clinical features and pathogenesis.
  Type I – commonly in pre- and peri-menopausal women, are more common in patients with endometrial hyperplasia and unopposed estrogen exposure. Type I endometrial cancers are often low-grade, minimally invasive and carry a good prognosis. Type II – occur in older, post-menopausal women, they are often high-grade, with deep invasive and carry a poorer prognosis.
• b) SarcomaIn contrast to endometrial carcinomas, the uncommon endometrial stromal sarcomas are cancers that originate in the non-glandular connective tissue of the endometrium. Uterine carcinosarcoma, formerly called Malignant mixed müllerian tumor, is a rare uterine cancer that contains cancerous cells of both glandular and sarcomatous appearance – in this case, the cell of origin is unknown

B) Signs and symptoms -

• 1. Vaginal bleeding and/or spotting in postmenopausal women.
• 2. Abnormal uterine bleeding, abnormal menstrual periods.
• 3. Bleeding between normal periods in premenopausal women in women older than 40: extremely long, heavy, or frequent episodes of bleeding (may indicate premalignant changes).
• 4. Anemia, caused by chronic loss of blood
• 5. Lower abdominal pain or pelvic cramping. Urinary incontinence
• 6. Thin white or clear vaginal discharge in postmenopausal women
• 7. Unexplained weight gain

C) Risk Factor -

• 1. Obesity, Hypertension, Diabetes
• 2. High levels of estrogen, Endometrial hyperplasia
• 3. Polycystic ovary syndrome
• 4. Nulliparity (never having carried a pregnancy) and Infertility (inability to become pregnant)
• 5. Early menarche (onset of menstruation) and Late menopause (cessation of menstruation)
• 6. Endometrial polyps or other benign growths of the uterine lining
• 7. Tamoxifen, Pelvic radiation therapy
• 8. Breast cancer, Ovarian cancer, Anovulatory cycles
• 9. Age over 35, Lack of exercise, Heavy daily alcohol consumption

D) Diagnosis -

• 1. Clinical evaluation - Changes in the size, shape or consistency of the uterus and/or its surrounding, supporting structures may exist when the disease is more advanced.
• 2. A Pap smear may be either normal or show abnormal cellular changes.
• 4. Hysteroscopy allows the direct visualization of the uterine cavity and can be used to detect the presence of lesions or tumours.
• 5. Transvaginal ultrasound to evaluate the endometrial thickness in women with postmenopausal bleeding is increasingly being used to evaluate for endometrial cancer
• 6. Further evaluation – Imaging studies, such as CT scans, to evaluate for extent of disease, the tumor marker CA-125 is checked, since this can predict advanced stage disease

E) Pathology

The histopathology of endometrial cancers is highly diverse. The most common finding is a well-differentiated endometrioid adenocarcinoma, Frank adenocarcinoma may be distinguished from atypical hyperplasia by the finding of clear stromal invasion. With progression of the disease, the myometrium is infiltrated. However, other subtypes of endometrial cancer exist and carry a less favorable diagnosis such as the uterine papillary serous carcinoma and the clear cell carcinoma.

Staging

Endometrial carcinoma is surgically staged using the FIGO cancer staging system. Is as follows:

• IA-Tumor confined to the uterus, no or < ½ myometrial invasion
• IB-Tumor confined to the uterus, > ½ myometrial invasion
• II-Tumor involves the uterus and the cervical stroma
• IIIA-Tumor invades serosa or adnexa
• IIIB-Vaginal and/or parametrial involvement
• IIIC1-Pelvic lymph node involvement
• IIIC2- Para-aortic lymph node involvement, with or without pelvic node involvement
• IVA-Tumor invasion bladder mucosa and/or bowel mucosa
• IVB-Distant metastases including abdominal metastases and/or inguinal lymph nodes

Traeatment

The primary treatment is surgical. Surgical treatment should consist of, at least, cytologic sampling of the peritoneal fluid, abdominal exploration, palpation and biopsy of suspicious lymph nodes, abdominal hysterectomy, and removal of both ovaries (bilateral salpingo-oophorectomy). Lymphadenectomy, or removal of pelvic and para-aortic lymph nodes, is sometimes performed for tumors that have high risk features, such as pathologic grade 3 serous or clear-cell tumors, invasion of more than 1/2 the myometrium, or extension to the cervix or adnexa. Sometimes, removal of the omentum is also performed. Women with stage 1 disease who are at increased risk for recurrence and those with stage 2 disease are often offered surgery in combination with radiation therapy. Chemotherapy may be considered in some cases, especially for those with stage 3 and 4 disease. Hormonal therapy with progestins and antiestrogens has been used for the treatment of endometrial stromal sarcomas.

H) Prognosis -

Approximately 8,200 people die annually from endometrial cancer. The 5-year survival rates for endometrial adenocarcinoma following appropriate treatment are 80%. Most women, over 75%, have FIGO stage 1 or 2, which have the best prognosis. Recurrence of early stage endometrial cancer ranges from 3 to 17%, depending on primary and adjuvant treatment. Most recurrences (70%) occur in the first three years.

Over 70% of endometrial cancer survivors has a co-morbidity and on average they have between 2 and 3 co-morbidities. It has been shown that obesity has a negative consequence for the quality of life of endometrial cancer survivors.

III) OVARIAN CANCER

A woman runs a great risk of developing ovarian cancer during her lifetime and even higher chances of getting killed by it. It is one of the leading causes of cancer death in women. Age-standardized incidence rates (ASR) for ovarian cancer varied from 0.9 to 8.4 per 100,000 person years. Quite often, women don’t show any signs of it and its initial symptoms mimic gastrointestinal illness and indigestion. The main treatments for ovarian cancer are surgery, chemotherapy and radiation or a combination of the three.

A) Signs and symptoms

Signs and symptoms of ovarian cancer are frequently absent early on and when they exist they may be subtle. In most cases, the symptoms persist for several months before being recognized and diagnosed. Most typical symptoms include: bloating, abdominal or pelvic pain, difficulty eating, and possibly urinary symptoms. If these symptoms recently started and occur more than 12 times per month the diagnosis should be considered

Other findings include an abdominal mass, back pain, constipation, tiredness and a range of other non-specific symptoms, as well as more specific symptoms such as abnormal vaginal bleeding or involuntary weight loss. There can be a build-up of fluid (ascites) in the abdominal cavity. Ovarian cancer is associated with age, family history of ovarian cancer, anaemia, abdominal pain, abdominal distension, rectal bleeding, postmenopausal bleeding, appetite loss and weight loss.

B) Cause -

In most cases, the exact cause of ovarian cancer remains unknown. The risk of developing ovarian cancer appears to be affected by several factors:

• 1. Older women who have never given birth and history of cancer in family.
• 2. Hereditary forms of ovarian cancer – associated with BRCA1 and BRCA2
• 3. Infertile women and those with a condition called endometriosis, and those who use postmenopausal estrogen replacement therapy are at increased risk.

C) Harmones -

Combined oral contraceptive pills are a protective factor. Early age at first pregnancy, older age of final pregnancy and the use of low dose hormonal contraception have also been shown to have a protective effect. The risk is also lower in women who have had their fallopian tubes blocked surgically (tubal ligation). Tentative evidence suggests that breastfeeding lowers the risk of developing ovarian cancer.

The ovaries contain eggs and secrete the hormones that control the reproductive cycle. Removing the ovaries and the fallopian tubes greatly reduces the amount of the hormones estrogen and progesterone circulating in the body. This can halt or slow breast and ovarian cancers that need these hormones to grow.