Overview of Cervical Cancer

Worldwide, cervical cancer is the fourth most frequent cancer in women with an estimated 570 000 new cases in 2018. Of the estimated more than 311 000 deaths from cervical cancer every year, more than 85% of these occur in low and middle-income countries. Women living with HIV are six times more likely to get cervical cancer compared to women without HIV. 

Fifty years ago, carcinoma of the cervix was the leading cause of cancer deaths in the United States, but the death rate has declined by two thirds. No other form of cancer documents the benefits of effective screening, early diagnosis, and curative therapy than cervical cancer. Much credit of this dramatic gain is contributed to the effectiveness of the pap smear test in detecting early low stage precursor lesions. The slow progression from precursor lesion to invasive carcinoma also contributes to it. When diagnosed, cervical cancer is one of the most successfully treatable forms of cancer, as long as it is detected early and managed effectively. Cancers diagnosed in late stages can also be controlled with appropriate treatment and palliative care. 

Almost all cervical cancer cases are linked to infection with high-risk human papillomaviruses (HPV), a widespread virus transmitted through sexual contact. Most sexually active women and men will be infected at some point in their lives, and some may be repeatedly infected. The peak time for acquiring infection for both women and men is shortly after becoming sexually active. HPV is sexually transmitted, but penetrative sex is not required for transmission. Skin-to-skin genital contact is a well-recognised mode of transmission. There are many types of HPV, and many do not cause problems. HPV infections usually clear up without any intervention within a few months after the acquisition, and about 90% clear within two years. A small proportion of infections with certain types of HPV can persist and progress to cervical cancer. It takes 15 to 20 years for cervical cancer to develop in women with normal immune systems. It can take only 5 to 10 years in women with weakened immune systems, such as those with untreated HIV infection. HPV are DNA viruses and grouped into high and low oncogenic risk. Non-cancer-causing types of HPV (especially types 6 and 11) can cause genital warts and respiratory papillomatosis. There are 15 high-risk HPV identified, but HPV 16 alone accounts 60% cervical cancer cases and HPV 18 accounts another 10%. HPV types also cause a proportion of cancers of the anus, vulva, vagina, penis, and oropharynx, which are preventable using similar primary prevention strategies as those for cervical cancer. 

HPV infects immature basal cells of the squamous epithelium in areas of epithelial breaks or immature metaplastic squamous cells at the squamocolumnar junction (transformation zone). The ability of HPV is that they are able to interfere the activity of tumour suppressor genes: RB and Tp53.  

Risk factors for HPV persistence and development of cervical cancer 

  1. HPV type – its oncogenicity or cancer-causing strength; 
  2. Immune status – people who are immunocompromised, such as those living with HIV, are more likely to have persistent HPV infections and a more rapid progression to pre-cancer and cancer; 
  3. Coinfection with other sexually transmitted agents, such as those that cause herpes simplex, chlamydia and gonorrhoea; 
  4. Parity (number of babies born) and young age at first birth; 
  5. Tobacco smoking;  
  6. Multiple sexual partners;
  7.  Not using barrier contraception.

Awareness about cervical health and cancer and its prevention is highly important because it is an easily preventable and curable cancer. Awareness can be generated through various means of mass communication.  

Comprehensive cervical cancer control includes primary prevention (vaccination against HPV), secondary prevention (screening and treatment of precancerous lesions), tertiary prevention (diagnosis and treatment of invasive cervical cancer), and palliative care. Of utmost importance is primary prevention (preventing the occurrence of disease). It includes the following: 

●       Health information and warning about tobacco use  

●       Sex education tailored according to age and culture  

●       Condom promotion and provision 

●       Male circumcision 

●       HPV vaccination 

HPV vaccination, which requires multiple doses, was first recommended for girls in 2006 and for boys in 2011. Vaccination is routinely recommended at 11−12 years and can be started at age 9. For those not vaccinated at 11−12 years, vaccination is recommended for all persons through age 26 years. Two HPV vaccine doses, given 6 to 12 months apart, are recommended if the series is started before age 15. Three doses, to be completed within six months, are recommended for those who started vaccination at age 15 or over. Catch‐up HPV vaccination is recommended for all persons through age 26 years who are not adequately vaccinated. Providers should inform individuals aged 22 to 26 years who have not been previously vaccinated or who have not completed the series that vaccination at older ages is less effective in lowering cancer risk. Catch‐up HPV vaccination is not recommended for adults aged older than 26 years.    

Three HPV vaccines—9-valent HPV vaccine (Gardasil® 9, 9vHPV), quadrivalent HPV vaccine (Gardasil®, 4vHPV), and bivalent HPV vaccine (Cervarix®, 2vHPV)—have been licensed by the U.S. Food and Drug Administration (FDA). All three HPV vaccines protect against HPV types 16 and 18 that cause most HPV cancers.

●       Gardasil – targets HPV types 6, 11, 16 and 18 

●       Cervarix – targets HPV types 16 and 18 

●       Gardasil 9 – targets HPV types 6, 11, 16, 18, 31, 33, 45, 52 and 58 

The U.S. FDA has extensively tested the HPV vaccine to ensure patient safety. Side effects from the HPV vaccine are not serious and may include pain or redness at the injection site, dizziness, fainting, nausea, and headache. Data on the vaccine’s efficacy is available for about ten years following vaccination. Surveillance studies have demonstrated vaccine safety and efficacy with excellent antibody responses, suggesting long-lasting protected immunity. The greatest protection is achieved if the vaccine is given before becoming sexually active. However, patients with prior documented HPV infection—such as a history of genital warts or positive HPV on Pap smear—can still benefit from the vaccine, as it can provide protection from other HPV types that have not been acquired. HPV immunisation does not protect 100 percent against all HPV types known to cause cervical cancer, and it is not used as a treatment for clearing HPV infections acquired prior to immunisation. Cervical cancer screening is still indicated after vaccination. 

Among adults aged 18−26, the percentage who ever received one or more doses of human papillomavirus (HPV) vaccine increased from 22.1% in 2013 to 39.9% in 2018. The rate of adults aged 18−26 who received the recommended number of doses of HPV vaccine increased from 13.8% in 2013 to 21.5% in 2018. 

Most practice- and community-based interventions significantly increased HPV vaccination rates using varied approaches across diverse populations. To address the current suboptimal rates of HPV vaccination, future efforts should focus on programmes that can be implemented within healthcare settings, such as reminder and recall strategies and physician-focused measures, as well as the use of alternative community-based locations, such as schools. 

Screening is an important secondary prevention strategy. Cervical cancer screening involves testing for pre-cancer and cancer; more and more testing for HPV infection is performed. Testing is done among women who have no symptoms and may feel perfectly healthy. When screening detects an HPV infection or precancerous lesions, these can easily be treated, and cancer can be avoided. Screening can also detect cancer at an early stage, and treatment has a high potential for cure.  

Because precancerous lesions take many years to develop, screening is recommended for every woman from aged 30 and regularly afterwards (frequency depends on the screening test used). For women living with HIV who are sexually active, screening should be done earlier: as soon as they know their HIV status.  

Screening has to be linked to the treatment and management of positive screening tests. Screening without proper management in place is not ethical. 

There are three different types of screening tests that WHO currently recommends: 

●       HPV DNA testing for high-risk HPV types 

●       Visual inspection with Acetic Acid (VIA) 

●       Conventional (Pap) test and liquid-based cytology (LBC)  

Cervical cancer screening mainly includes the Pap test and, for some women, an HPV test. Both tests use cells taken from the cervix. The screening process is simple and fast. You lie on an exam table, and a speculum is used to open the vagina. The speculum gives a clear view of the cervix and upper vagina. 

Cells are removed from the cervix with a brush or other sampling instrument. The cells usually are put into a special liquid and sent to a laboratory for testing: 

●      For a Pap test, the sample is examined to see if abnormal cells are present. 

●    For an HPV test, the sample is tested for the presence of 13–14 of the most common high-risk HPV types. 

●    Women aged 21–29 years should have a Pap test alone every three years. HPV testing is not recommended. 

●     Women aged 30–65 years should have a Pap test and an HPV test (co-testing) every five years (preferred). It also is acceptable to have a Pap test alone every three years. 

You should stop having cervical cancer screening after age 65 years if: 

●       You do not have a history of moderate or severe abnormal cervical cells or cervical cancer, and 

●       You have had either three negative Pap test results in a row or two negative co-test results in a row within the past ten years, with the most recent test performed within the past five years. 

●       Women who have a history of cervical cancer, are infected with human immunodeficiency virus (HIV), have a weakened immune system, or who were exposed to diethylstilbesterol (DES) before birth may require more frequent screening and should not follow these routine guidelines. 

●       For the treatment of precancerous lesions, WHO recommends the use of cryotherapy or thermal ablation and Loop Electrosurgical Excision Procedure (LEEP) when available. For advanced lesions, women should be referred for further investigations and adequate management. 

When a woman presents symptoms of suspicion for cervical cancer, she must be referred to an appropriate facility for further evaluation, diagnosis, and treatment. 

Symptoms of the early stage of cervical cancer may include: 

●       Irregular blood spotting or light bleeding between periods in women of reproductive age; 

●       Post-menopausal spotting or bleeding; 

●       Bleeding after sexual intercourse; and 

●       Increased vaginal discharge, sometimes foul-smelling. 

As cervical cancer advances, more severe symptoms may appear, including: 

●       Persistent back, leg and pelvic pain; 

●       Weight loss, fatigue, loss of appetite; 

●       Foul-smell discharge and vaginal discomfort; and 

●       Swelling of a leg or both lower extremities. 

Diagnosis of cervical cancer must be made by histopathologic examination. Staging is done based on tumour size and spread of the disease within the pelvis and to distant organs. Treatment depends on the stage of the disease, and options include surgery, radiotherapy, and chemotherapy. Palliative care is also an essential element of cancer management to relieve unnecessary pain and suffering due to the disease.   

Awareness about cervical health and cancer and its prevention is highly important because it is an easily preventable and curable cancer. In today’s time, the focus needs to shift towards increasing vaccination rates as not many individuals in the reproductive age group are not aware of the existence of vaccination or apprehensive about it. Physicians must thrive on educating individuals about vaccination and screening of cervical cancer.

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