Human papillomavirus (HPV) infection and cervical cancer

Human papillomavirus (HPV) is a group of viruses that is common throughout the world. HPV is one of the causative agents in the sexually transmitted infections (STIs) in men and women with and without clinical lesions a. HPV is transmitted through sexual contact and is the most common viral infection of the reproductive tract.

The main burden of HPV-related disease is due to cervical cancer. HPV infection is a well-established cause of cervical cancer and a relevant factor in other anogenital cancers (anus, vulva, vagina and penis) and head and neck cancers. HPV is also responsible for other diseases such as recurrent juvenile respiratory papillomatosis (a disease in which tumours grow in the air passages leading from the nose and mouth into the lungs) and genital warts in men and women. Genital warts are very common and highly infectious.

Cervical cancer is the fourth most common cancer in women worldwide and second most common cancer in women living in less developed regions. World Health Organization (WHO) estimated 530 000 new cases of cervical cancer globally (estimations for 2012), with approximately 270 000 deaths (representing 7.5% of all female cancer deaths). More than 85% of these deaths occurred in low- and middle-income countries.

About 80% of cancer cases attributable to HPV were in developing countries.  The highest estimated incidence rates for cervical cancer are in sub-Saharan Africa, Melanesia, Latin America and the Caribbean, south-central Asia and south-east Asia.

India has a population of 436.76 million women aged 15 years and older who are at risk of developing cervical cancer. Every year 122844 women are diagnosed with cervical cancer and 67477 die from the disease (estimations for 2012). In India cervical cancer is the second most common cancer among women and also the second most common cancer among women between 15 and 44 years of ageb.

Based on Indian studies (performing HPV detection tests in cervical samples) about 5.0% of women in the general population are found to carry cervical HPV-16/18 infection at a given time, and 82.7% of invasive cervical cancers showed the presence of HPVs 16 or 18.(Systematic reviews and meta-analyses of the literatures by ICO HPV Information Centre)b.

Other epidemiological risk factors for cervical cancer are early age at marriage, multiple sexual partners, multiple pregnancies, poor genital hygiene, malnutrition, use of oral contraceptives, and lack of awareness.

India also has the highest (age standardized) incidence rate as 22 (per 100,000 women per year) of cervical cancer in South Asia (estimations for 2012), compared to 19.2 in Bangladesh, 13 in Sri Lanka, and 2.8 in Iran.

HPV types 16 and 18 are responsible for about 70% of all cervical cancer cases worldwide. HPV vaccines that prevent against HPV 16 and 18 infections are now available and have the potential to reduce the incidence of cervical and other anogenital cancers.

References-

a.nhp.gov.in/diseasesexually-transmitted-infections

b. hpvcentre.net/statistics/reports/IND.pdf (Human Papillomavirus and Related Diseases Report, India, ICO Information Centre on HPV and Cancer (HPV Information Centre) 2015)

who.int/bulletin/volumes/85/9/06-038414/en/

who.int/mediacentre/factsheets/fs380/en/

who.int/immunization/diseases/hpv/en/

Most of the HPV infections cause no symptoms and subsides spontaneously by body’s immune system. More than 90% of infections are cleared within two years. 

However persistent genital HPV infection (HPV types 16 and 18) can cause precancerous lesions in the cervix. If precancerous lesions are not treated, they may progress to cervical cancer.

This can take 15 to 20 years or more for a persistent infection with a high-risk HPV type to develop cervical cancer 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.

Symptoms of cervical cancer appear only after the cancer has reached an advanced stage.  

Symptoms may be:

  • irregular, intermenstrual (between periods) or abnormal vaginal bleeding after sexual intercourse or  bleeding after menopause;
  • vaginal discomfort or odourous discharge from vagina, the discharge may contain some blood and may occur between periods or after menopause;
  • Pain during sex;
  • back, leg or pelvic pain;
  • fatigue, weight loss, loss of appetite;
  • a single swollen leg.

More severe symptoms may develop at advanced stages of cervical cancer.

Non-cancer causing types of HPV (especially types 6 and 11) can cause genital warts and respiratory papillomatosis (a disease in which tumours grow in the air passages leading from the nose and mouth into the lungs). Although these conditions very rarely result in death, they may cause significant occurrence of disease. Genital warts are very common and highly infectious.

References-

who.int/mediacentre/factsheets/fs380/en/

webmd.com/cancer/cervical-cancer/

HPV is a member of the family Papillomaviridae. They are small, non-enveloped deoxyribonucleic acid (DNA) viruses. They are classified according to DNA sequencing. There are more than 100 types of HPV, of which at least 13 are cancer-causing (also known as high risk type) including genotypes 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 66. The types of HPV that cause genital warts are different from the types that can cause cancer.

The time period between the oncogenic (cancer causing) HPV infection and the invasive cervical cancer is 15–20 years. In women with weakened immune systems, such as those with untreated HIV infection, cancer can develop within five to ten years.

HPV infections usually clear up without any intervention within a few months after acquiring the infection, and about 90% clear within 2 years. A small proportion of infections with certain types of HPV can persist and progress to cancer.

Mode of transmission –

HPV is mainly transmitted through sexual contact and most people are infected with HPV shortly after the onset of sexual activity. Skin-to-skin genital contact can transmit the infection; penetrative sex is not required for transmission.

Risk factors for HPV persistence and development of cervical cancer-

  • Early first sexual intercourse
  • Multiple sexual partners
  • High parity
  • Long-term use of hormonal contraceptives
  • Tobacco use
  • Immune suppression (for example, HIV-infected individuals are at higher risk of HPV infection and are infected by a broader range of HPV types)
  • Low socioeconomic status, poor hygiene and diet low in antioxidants
  • Co-infection with Chlamydia trachomatis and Herpes simplex virus type-2

References-

who.int/mediacentre/factsheets

ncbi.nlm.nih.gov/pmc/articles/

cdc.gov/std/tg2015/hpv.htm

who.int/bulletin/volumes/

Most of the HPV infections and cervical cancer in its early stage show no clinical signs and symptoms; precancerous lesions and early cancers can be detected by screening tests. Screening is recommended for every woman from aged 30 to 49 years at least once in a lifetime and ideally more frequently (WHO).

United States Preventive Services Task Force (USPSTF) and the American Cancer Society (ACS) guidelines recommend testing every three years for women in age group 21-65 years; (routine cervical cancer screening for women less than 21 and over 65 years is not recommended). Five-year screening interval is recommended for women in age group 30-65 years when screening is done with a combination of Pap test and human papillomavirus (HPV) test.

Screening for cervical cancer-

There are 3 different types of screening tests-

  • Conventional (Pap) test and liquid-based cytology (LBC) - The Pap test is used to detect abnormal cells that may develop into cancer if left untreated. In a conventional Pap test, the specimen (or smear) is placed on a glass microscope slide and a fixative is added. In an automated liquid-based Pap cytology test, cervical cells collected with a brush or other instrument are placed in a vial of liquid preservative. One advantage of liquid-based testing is that the same cell sample can also be tested for the presence of high-risk types of HPV, a process known as “Pap and HPV co-testing.
  • Visual inspection with Acetic Acid (VIA) - Doctor may apply a dilute acetic acid solution (vinegar solution) to the cervix, which causes abnormal areas to turn white. Further a biopsy can be taken from abnormal area.
  • HPV testing for high-risk HPV type- HPV testing is used to look for the presence of high-risk HPV types in cervical cells

References-

cancer.gov/types/cervical/pap-hpv-

who.int/mediacentre/factsheets/

acog.org/~/media/districts/district

If abnormal cells or lesions detected during screening tests, treatment is needed to excise abnormal cells or lesions. It includes cryotherapy (destroying abnormal tissue on the cervix by freezing it) or Loop electrosurgical excision procedure (LEEP) when the patient is not eligible for cryotherapy. 

If signs of cervical cancer are present, treatment options for invasive cancer include surgery, radiotherapy and chemotherapy.

References-

apps.who.int/iris/bitstream/

Complications of HPV infection-

  • cervical cancer,  
  • other anogenital cancers( anus, vulva, vagina and penis),
  • head and neck cancers,
  • recurrent juvenile respiratory papillomatosis, 
  • genital warts.

Reference-

who.int/mediacentre/factsheets/

Cervical cancer prevention and control: A comprehensive approach-

WHO recommends a comprehensive approach to cervical cancer prevention and control. Comprehensive approach should be multidisciplinary, including components from community education, social mobilization, vaccination, screening, treatment and palliative care.

Primary prevention begins with HPV vaccination of girls aged 9-13 years, before they become sexually active. Two HPV vaccines are there - a bivalent and a quadrivalent vaccine.

The quadrivalent vaccine gives 100% protection against infection from HPV types 16 and 18, which are responsible for around 70% of all cervical cancers. It also protects against HPV types 6 and 11 that cause genital warts.

The vaccination schedule depends on the age of the vaccine recipient. WHO (March, 2016)a recommended schedule for both HPV vaccines is as-

  • Females <15 years at the time of first dose: a 2-dose schedule (0, 6 months) is recommended.

             (If the interval between doses is shorter than 5 months, then a third dose should be given at least 6 months after the first dose).

  • Females ≥15 years at the time of first dose: a 3-dose schedule (0, 1-2, 6 months) is recommended.
  • 3-dose schedule is recommended for those known to be immunocompromised and/or HIV-infected. (The vaccines cannot treat HPV infection or HPV-associated disease such as cancer, but it prevents the infection).

Some countries are vaccinating boys for prevention of genital cancers and genital warts in males.

Two vaccines (bivalent and a quadrivalent vaccine), which are licensed in more than a 120 countries, are available in India with the approval of Drug Controller General of India (DCGI). 63 countries have also included HPV vaccination to girls in their national immunization programmes. HPV vaccination for girls is recommended by Indian Academy of Pediatrics (IAP) and Federation of Obstetric and Gynaecological Societies of India (FOGSI) and Cancer Foundation of India b.

Other preventive interventions may be recommended to boys and girls as appropriate are:

  • education about safe sexual practices, including delayed start of sexual activity;
  • promotion and provision of condoms for those already engaged in sexual activity;
  • warnings about tobacco use, which often starts during adolescence, and which is an important risk factor for cervical and other cancers; and
  • male circumcision.

Male circumcision and the use of condoms have shown a significant protective effect against HPV transmission.

Secondary prevention- It includes Screening (early diagnosis) and treatment.

Cervical cancer screening should be an essential part of a woman’s routine health care. It detects pre-cancer and cancer among women who have no symptoms and may feel perfectly healthy. Important aspect of screening is that both precancerous lesions and early cervical cancers can be treated very successfully at this stage.

Women who are sexually active should be screened for abnormal cervical cells and pre-cancerous lesions. United States Preventive Services Task Force (USPSTF) and the American Cancer Society (ACS) guidelines recommend testing every three years for women in age group 21-65 years; (routine cervical cancer screening for women below 21 and over 65 is not recommended). Five-year screening interval is recommended for women in age group 30-65 years, when screened with a combination of Pap test and human papillomavirus (HPV) test.

The high mortality rate from cervical cancer globally (52%) could be reduced by effective screening and treatment programme. WHO has provided guidelines on Screen-and-treat strategy to prevent cervical cancer c.

References-

a. who.int/immunization/diseases/hpv/en/

b. cancerfoundationofindia.org/meetingssymposium/pdf/

c.apps.who.int/iris/bitstream/eng.pdf

   who.int/mediacentre/factsheets/fs380/en/

  hpvcentre.net/statistics/reports/IND.pdf

  • PUBLISHED DATE : Apr 08, 2016
  • PUBLISHED BY : Zahid
  • CREATED / VALIDATED BY : Dr. Aruna Rastogi
  • LAST UPDATED ON : Apr 08, 2016

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