Cancer, Cervical

Article Author:
Josephine Fowler
Article Editor:
Brian Jack
Updated:
9/9/2019 7:49:37 PM
PubMed Link:
Cancer, Cervical

Introduction

Cervical cancer continues to be listed among the top gynecologic cancers worldwide. According to current data, it is ranked fourteenth among all cancers and fourth-ranked cancer among women worldwide.[1] Cervical cancer intervention focuses on primary and secondary prevention. [2] Primary prevention and screening is the best method to decrease the burden of cervical cancer and to decrease mortality. In the United States and other developing countries, most screening and diagnostic efforts are directed towards early identification of high-risk human papillomavirus (HPV) lesions through HPV testing and Pap smears. Although HPV testing is not recommended in women younger than 30 years of age, low-risk younger women should begin screening with Pap tests at age 21 and continue until age 65, according to the United States Preventive Services Task Force recommendations. Newer recommendations offer 3 to 5-year intervals between screening based on prior results and the use of pap and HPV co-testing. [3][4] Since cervical cancer is a sexually transmitted infection, it is a preventable disease. Targeted education, screening, and intervention can reduce the burden of disease. Like many diseases and cancers, disparities exist in screening rates, early diagnosis, and timely treatment. Screening rates tend to be less in low socioeconomic and low resource areas with ethnic and age variations. Studies show that women with obesity and chronic disease may also have lower rates of cervical and breast cancer screening. A study on ethnic minority women in the United Kingdom reports several barriers to screening including lack of awareness, fear, embarrassment, and shame, and low perceived risk.[5] One study reviewing the barriers for Haitian women revealed socioeconomic barriers, language barriers, and limited understanding of health and disease. [6]  In the United States, cervical cancer mortality is disproportionately higher for African American women. Since 2006, vaccination has been available for the prevention of cervical cancer. Vaccination can improve cancer death rates in underdeveloped countries where resources may not be available for routine screening and in populations with higher mortality rates.

Etiology

Current literature reports that Human papillomavirus (HPV) is found in the majority of sexually active people at some point during their life. There are more than 130 types of known HPV with 20 HPV types identified as cancer-related. HPV-related cervical dysplasia rates are only known in women since men are not screened outside of research protocols. HPV 16 and 18 are the most commonly found HPV in invasive cervical cancer. Population-based HPV prevalence studies show that the greatest prevalence of high-risk HPV occurs in the young adult period before 25 years of life and cervical cancer death peaks in the middle age period of 40 to 50 years of life. Studies have shown that HPV-related cervical disease in women younger than 25 years old is largely self-limiting. However, those with co-infection may be less likely to have spontaneous clearance and progress to cancer. Risks factors for HPV and cervical cancer include age at first intercourse, multiple sexual partners, smoking, herpes simplex, HIV, co-infection with other genital infections, and oral contraceptive use. HPV is transmitted by skin to skin contact including during sexual intercourse, hand to genital organ contact, and oral sex.[7][8]

Epidemiology

Globally, there are more than 500,000 new cases of cervical cancer annually. Approximately 250,000 women die of cervical cancer annually.  In the United States, about 4000 women die from cervical cancer annually with African Americans, Hispanics, and women in low-resource areas having higher disparities in evidenced-based care and a much higher mortality rate.[9][10]HPV, the causative agent is a sexually transmitted viral infection. Cervical cancer mortality is higher among women who have not been screened in the last five years and those women without consistent follow-up post identification of a precancerous lesion. Trends continue to show that women with the highest risk of mortality may be less likely to receive a vaccination that could potentially prevent cervical cancer.

Pathophysiology

HPV is the causative agent in cervical cancer. More than 75 percent of cases are due to high-risk HPV 16 and 18.[11] Although there are more than a half-million cases of HPV identified annually, most are low-grade infections and will spontaneously resolve within two years. Progression of high-grade lesions and cancer are seen in the presence of other carcinogenic factors such as listed above.

History and Physical

The patient with cervical cancer is usually asymptomatic in the early stages. The history and physical must include sexual history including the age of first sexual encounter. Sexual history includes questions about postcoital bleeding and pain during intercourse. The history includes questioning about previous sexually transmitted infections, the number of lifetime partners, previous history of HPV infection, history of human immunodeficiency virus, use of tobacco, and whether the patient has had a previous vaccination against HPV. Women should be asked about menstrual patterns and any abnormal bleeding, persistent vaginal discharges, irritations, or known cervical lesions. The physical exam must include a full evaluation of the external and internal genitalia. In women with cervical cancer, the exam findings might include a friable cervix, lesions, erosions, or bleeding with examination and fixed adnexa.

Evaluation

According to the United States Preventative Services Task Force (USPTF), Pap screening is recommended beginning at age 21 years of age. HPV testing begins at age 30 in conjunction with Pap smear cytology. Screening is recommended every three years for women with continued normal screening and those low risk for cervical cancer. For women over 30 years of age, cytology can be every five years with HPV testing. Level A recommendation or women with low-risk status and consistent normal screenings can discontinue cervical cancer cytology and HPV testing at age 65. Women who have had a total abdominal hysterectomy including removal of the cervix for benign disease do not require further screening.[4]

Treatment / Management

Precancerous lesions are managed conservatively for those women younger than 25 years. The majority of abnormal findings in women younger than 25 are low-risk cervical dysplasia and will resolve spontaneously. Colposcopy evaluates persistent, abnormal cytology or lesions suspected to be greater than low risk. These are managed according to findings. Low-risk lesions may be watched and reevaluated more frequently, and high-risk lesions are treated based on size, location, and staging. Cryotherapy or excision is done to manage pre-cancerous lesions that are limited in size and depth. Conization, laser or Loop Electrosurgical Excision Procedure (LEEP) are used in managing those lesions that include the endocervical canal and are more extensive. LEEP may provide better visualization of the squamocolumnar junction and provide the benefit of less bleeding in the outpatient setting. [12] If cancer is diagnosed, the next step in management is staging to determine further treatment. Staging is based on findings and results from examination, tissue findings, imaging, and reported signs and symptoms. Grading is based on the size and depth of cancer and signs of spread to other organs. Treatment of early-stage disease includes a radical hysterectomy. For women who desire pregnancy with early-stage disease, conization may be the initial treatment. Chemotherapy and radiation are usually the next steps in treatment after hysterectomy to slow the growth of cancer.

Differential Diagnosis

Evaluating visible cervical lesions for cervical cancer is important. However, most cervical cancer will not present with an overt mass in early stages and as discussed above is asymptomatic. Other possible causes of cervical lesions or abnormal bleeding include sexually transmitted infections, cervical fibroids, endometriosis, and cervical polyps. Diagnosis may require further testing and evaluation of symptoms to determine whether the disease is related to cervical cancer. In some cases, diagnostic biopsy is needed to finalize the diagnosis. Rarely, metastatic cancer may be identified on the uterine cervix during a routine pap smear.[13]

Prognosis

The estimated effectiveness of HPV vaccination is 90 percent. [14] Inconsistent screening is an independent risk factor for the late diagnosis of cervical cancer. [15] The five-year survival rate for cervical cancer can approach 92 percent. The higher stage at presentation decreases survival and increases the chance of recurrence. African American women tend to have the highest mortality and lowest survival rate. The survival rate may be less than 50 percent. Contributing factors to differences in outcomes may include differences in the delivery of evidence-based care, later stage of diagnosis, lymph node spreading, age, and size and invasion of the tumor at the time of diagnosis. [10][16]

Complications

Complications of advanced disease and associated treatments are similar to other cancers. Complications may include renal failure, hydronephrosis, pain, lymphedema, bleeding disorder, and fistulas. [17] Rare sequelae may include orbital index and blindness. [18]

Deterrence and Patient Education

Both traditional methods of patient education and innovative methods can increase awareness of cervical cancer and the need for prevention and early screening. [19][20] The literature shows that doctors may not be recommending or discussing HPV vaccination with patients. Women and parents also have vaccination fears. In high-risk populations, additional education to physicians may increase awareness, prevention, and screening among those women at risk for highest mortality.[21]  Although, a patient may prefer health system education from the provider. Additional education including culturally sensitive information, appropriate language to reach low health literacy populations, and targeted efforts to women not yet sexually active are needed to expand patient education and awareness of cervical cancer prevention and screening beyond the clinical setting through community outreach. [22][23]

Pearls and Other Issues

Primary prevention includes vaccination to prevent cervical cancer. There is a quadrivalent vaccine that prevents not only cervical cancer but also prevents genital warts. The recommended age for vaccination is from 9 to 45 years old for females. It is approved for females ages 9 to 45 and is also recommended for males. Health promotion aimed at vaccination can have a major impact on cervical cancer mortality in women in low resource areas and those who are in high-risk ethnic groups. A vaccine that only covers HPV 16 and 18 is no longer marketed in the United States. However, its use may continue in other areas outside of the United States.

Enhancing Healthcare Team Outcomes

The interdisciplinary team care in the prevention, screening, treatment, and management of cervical cancer can improve awareness, screening, and management of cervical cancer. The use of pubic education can increase awareness about cervical cancer prevention and screening and the importance of identifying precancerous lesions. [24][25][26] Primary care providers performing cervical cancer screening, colposcopies, and LEEP procedures, must have ongoing dialogues with gynecology about findings, suspicious lesions, outcomes, and management and treatment. Organized protocols and guidelines across the system can lead to better outcomes in increasing awareness, screening, management and treatment, and follow-up. Developing a culturally sensitive system directed at increasing patient-centered education will also require the input of diverse staff and providers with language skills, cultural competency, lab, and nursing.

The interprofessional team can optimize the treatment of patients through communication and coordination of care. Primary care physicians, gynecologists, radiation oncologists, and nurse practitioners provide diagnoses and care plans. Specialty care ambulatory care and oncology nurses should work with the team for coordination of care and are involved in patient education. They should provide feedback to the rest of the team. Pharmacists should evaluate vaccinations, medications prescribed, recognize drug-drug interactions, provide patient education, and monitor compliance. The team can thus improve outcomes for patients with cervical cancer. [level V]


References

[1] Brisson M,Drolet M, Global elimination of cervical cancer as a public health problem. The Lancet. Oncology. 2019 Feb 19;     [PubMed PMID: 30795952]
[2] Pimple S,Mishra G, Global strategies for cervical cancer prevention and screening. Minerva ginecologica. 2019 Feb 22;     [PubMed PMID: 30808155]
[3] Cervical Cancer Screening Every 5 Years OK. Cancer discovery. 2018 Oct;     [PubMed PMID: 30206109]
[4] Farghaly H,Bourgeois D,Houser PM,Padmanabhan V,Lage JM,Hoda RS, Routine vaginal Pap test is not useful in women status-post hysterectomy for benign disease. Diagnostic cytopathology. 2006 Sep;     [PubMed PMID: 16900480]
[5] Foran C,Brennan A, Prevention and early detection of cervical cancer in the UK. British journal of nursing (Mark Allen Publishing). 2015 May 28-Jun 10     [PubMed PMID: 26018178]
[6] Pierre-Victor D,Stephens DP,Omondi A,Clarke R,Jean-Baptiste N,Madhivanan P, Barriers to HPV Vaccination Among Unvaccinated, Haitian American College Women. Health equity. 2018;     [PubMed PMID: 29904749]
[7] Manini I,Montomoli E, Epidemiology and prevention of Human Papillomavirus. Annali di igiene : medicina preventiva e di comunita. 2018 Jul-Aug;     [PubMed PMID: 30062377]
[8] Ghosh I,Mandal R,Kundu P,Biswas J, Association of Genital Infections Other Than Human Papillomavirus with Pre-Invasive and Invasive Cervical Neoplasia. Journal of clinical and diagnostic research : JCDR. 2016 Feb     [PubMed PMID: 27042571]
[9] Kuhn L,Denny L, The time is now to implement HPV testing for primary screening in low resource settings. Preventive medicine. 2017 May;     [PubMed PMID: 28279263]
[10] Rauh-Hain JA,Melamed A,Schaps D,Bregar AJ,Spencer R,Schorge JO,Rice LW,Del Carmen MG, Racial and ethnic disparities over time in the treatment and mortality of women with gynecological malignancies. Gynecologic oncology. 2018 Apr;     [PubMed PMID: 29605048]
[11] Wang X,Huang X,Zhang Y, Involvement of Human Papillomaviruses in Cervical Cancer. Frontiers in microbiology. 2018;     [PubMed PMID: 30546351]
[12] Senol T,Polat M,Ozkaya E,Karateke A, Comparison of Two Step LEEP and Cold Conisation For Cervical Intraepithelial Lesions to Decrease Positive Surgical Margins. Asian Pacific journal of cancer prevention : APJCP. 2016     [PubMed PMID: 27509969]
[13] Shachner TR,Van Meter SE, Metastatic melanoma of the uterine cervix diagnosed on cervical Pap smear: Case report and literature review. Diagnostic cytopathology. 2018 Dec     [PubMed PMID: 30354020]
[14] Spinner C,Ding L,Bernstein DI,Brown DR,Franco EL,Covert C,Kahn JA, Human Papillomavirus Vaccine Effectiveness and Herd Protection in Young Women. Pediatrics. 2019 Feb     [PubMed PMID: 30670582]
[15] Castellano T,Ding K,Moore KN,Landrum LM, Simple Hysterectomy for Cervical Cancer: Risk Factors for Failed Screening and Deviation From Screening Guidelines. Journal of lower genital tract disease. 2019 Apr     [PubMed PMID: 30817687]
[16] Rauh-Hain JA,Clemmer JT,Bradford LS,Clark RM,Growdon WB,Goodman A,Boruta DM 2nd,Schorge JO,del Carmen MG, Racial disparities in cervical cancer survival over time. Cancer. 2013 Oct 15     [PubMed PMID: 23913530]
[17] Pergialiotis V,Bellos I,Thomakos N,Haidopoulos D,Perrea DN,Kontzoglou K,Daskalakis G,Rodolakis A, Survival outcomes of patients with cervical cancer and accompanying hydronephrosis: A systematic review of the literature. Oncology reviews. 2019 Jan 14     [PubMed PMID: 30746036]
[18] Wadhwani M,Phuljhele S,Kumar R,Shameer A, Cervical carcinoma leading to orbital apex syndrome and blindness. BMJ case reports. 2019 Mar 1     [PubMed PMID: 30826777]
[19] Mendu S,Boukhechba M,Gordon JR,Datta D,Molina E,Arroyo G,Proctor SK,Wells KJ,Barnes LE, Design of a Culturally-Informed Virtual Human for Educating Hispanic Women about Cervical Cancer. International Conference on Pervasive Computing Technologies for Healthcare : [proceedings]. International Conference on Pervasive Computing Technologies for Healthcare. 2018 May     [PubMed PMID: 30555731]
[20] Nasser S,Berek J,Ullrich A,Giordano L,Sehouli J, A report on the Marrakech International Women's Cancer Days: dialogs and implications. International journal of gynecological cancer : official journal of the International Gynecological Cancer Society. 2019 Feb     [PubMed PMID: 30718317]
[21] Cunningham-Erves J,Forbes L,Ivankova N,Mayo-Gamble T,Kelly-Taylor K,Deakings J, Black mother's intention to vaccinate daughters against HPV: A mixed methods approach to identify opportunities for targeted communication. Gynecologic oncology. 2018 Jun     [PubMed PMID: 29588103]
[22] Mabelele MM,Materu J,Ng'ida FD,Mahande MJ, Knowledge towards cervical cancer prevention and screening practices among women who attended reproductive and child health clinic at Magu district hospital, Lake Zone Tanzania: a cross-sectional study. BMC cancer. 2018 May 16     [PubMed PMID: 29769124]
[23] Lai D,Bodson J,Davis FA,Lee D,Tavake-Pasi F,Napia E,Villalta J,Mukundente V,Mooney R,Coulter H,Stark LA,Sanchez-Birkhead AC,Kepka D, Diverse Families' Experiences with HPV Vaccine Information Sources: A Community-Based Participatory Approach. Journal of community health. 2017 Apr     [PubMed PMID: 27734247]
[24] Bayu H,Berhe Y,Mulat A,Alemu A, Cervical Cancer Screening Service Uptake and Associated Factors among Age Eligible Women in Mekelle Zone, Northern Ethiopia, 2015: A Community Based Study Using Health Belief Model. PloS one. 2016     [PubMed PMID: 26963098]
[25] Kung TH,Gordon JR,Abdullahi A,Barve A,Chaudhari V,Kosambiya JK,Kumar A,Gamit S,Wells KJ, "My husband says this: If you are alive, you can be someoneā€¦": Facilitators and barriers to cervical cancer screening among women living with HIV in India. Cancer causes & control : CCC. 2019 Apr     [PubMed PMID: 30809741]
[26] McPherson GS,Fairbairn-Dunlop P,Payne D, Overcoming Barriers to Cervical Screening Among Pacific Women: A Narrative Review. Health equity. 2019     [PubMed PMID: 30783634]