Cervical cancer - Role of Human Papilloma virus and screening

Dr Ayekpam Anil Meitei *

Worldwide, Cancer of the Cervix is the 4th most common cancer and commonest gynaecological cancer in women. It constitutes about 6.6% of all cancers diagnosed in female in 2018, that is about 5.7 lakh and constitutes 7.5% Cancer death in female (3.11 lakh), also the 4th commonest cancer death in female.

Cervical cancer ranks second in Incidence and mortality in low HDI setting (poor socio economic countries). It is still the most common diagnosed cancer in 28 countries; it is the second most common cancer in Indian women behind Breast Cancer.

Current estimates indicates approximately 1.32 lakh new cancer cases and 74000 deaths annually in India accounting to nearly 1/3rd of global cervical cancer death. Indian women face a 2.5% commutative life time risk of developing cervical cancer, that is, 1 in 40 women.

According to National Cancer Registry Programme, for the year 2012 to 2016, it is the 3rd most common cancer amongst women in Manipur behind Breast and Lung cancer. It constitutes 9.5% of cancer diagnosed amongst females in Manipur.

Sexually transmitted Human Papilloma Virus (HPV) Infection is the most important risk factor for cervical cancer.

Estimates suggest that more than 80% of the sexually active women acquire genital HPV by 50 years of age. It takes roughly 15 to 20 years from HPV Infection developing to precancerous lesion to Invasive cervical cancer.

Over 100 HPV serotypes have been discovered of which 15-20 serotypes can cause cervical cancer. Most common cancer causing serotype are 16, 18, 31, 33, 45, 52 and 58 of which HPV-16 and 18 contributes to nearly 70% of cervical cancers. Serotypes 6 and 11 contribute over 90% of benign genital infection such as genital warts.

Apart from cervical cancer, cancer causing HPV serotypes can cause Anal, Vulva, Vaginal, Penile and Oropharyngeal cancer. However the vast majority of HPV infections resolve spontaneously and only a minority (less than 1%) of HPV injection progresses to cancer. HPV is a necessary cause of cervical cancer, but is not a sufficient cause.

Other co-factors are necessary for progression from cervical HPV infection to cancer. Long term use of hormonal contraceptives, high parity, early initiation of sexual activity, multiple sex partners, tobacco smoking and co-infection with HIV, Chlamydia trachomatis, Herpes simplex virus type 2, Immunosuppression, low socio economic status, poor hygiene and diet low in antioxidants have been identified as established co-factors.

Vaccination against these cancer causing HPV serotype is an important strategy to reduce the incidence of cervical cancer. Developed Nations where routine vaccination against these cancer causing virus have been implemented have seen a reduced incidence of cervical cancer. Two vaccines licensed globally are currently available in India.

Cervarix is a bivalent vaccine against serotype 16 and 18. Gardasil-4 is a quadrivalent vaccine against serotype 6, 11, 16 and 18. A nonavalent vaccine Gardasil-9 got the USFDA approval in Dec 2014 has protection against 5 more HPV serotypes responsible for about 20% of Cervical Cancer. This nonavalent vaccine is not yet available in India.

The Advisory Committee on Immunization Practices (ACIP) recommends initiation of vaccination starting between 9 to 12 Years of age for girls and boys before the sexual debut. Vaccination is given as 0.5ml intramuscularly in the deltoid muscle or anterolateral thigh. A 2 dose regimen at 0 and 6 to 12 months is adequate if vaccinated before their 15th birthday.

A 3 dose regimen at 0, 1 to 2 and 6 months is recommended for teens and young adults who started after age 15 through 26 years (catch up vaccination) and for Immunocompromised persons. Vaccination after age 26 years are not routinely recommended. HPV vaccination after this age provides less benefit for several reasons including that more people in this age range have already been exposed to HPV.

The most common adverse reaction is local reaction like mild to moderate pain, swelling with redness at injection site and fever. The vaccine is not recommended for use in pregnant women. Vaccine is contraindicated in people with a history of immediate hypersensitivity to yeast or to any other vaccine component.

This vaccine provides protection in up to 90% against cancer caused by HPV 16 and 18, but not all cancer causing serotypes. Vaccines are not 100% protective against cervical cancer and are not a replacement for periodic cervical cancer screening. HPV vaccination is of public health importance. India currently does not include routine HPV vaccination in its immunization programme.

The Indian Academy of Paediatrics Committee on Immunization (IAPCOI) recommends offering HPV vaccine to all female who can afford the vaccine. A Quadrivalent vaccine currently is priced anywhere between 2500 to 4000 INR.

Screening test for cervical cancer

The best way to find cervical cancer early is to have regular screening test. The tests for cervical cancer screening test are the HPV test and the Pap test. These tests can be done alone or at the same time (Called a Co-test).

Regular screening has been shown to prevent cervical cancers and save lives. Early detection greatly improves the chances of successful treatment and can prevent any early cervical cell changes from becoming cancer. Being alert to any signs and symptoms can also help in avoiding unnecessary delay in diagnosis.

The HPV test

Doctors can now test for high risk cancer causing HPV serotypes by looking for pieces of their DNA in cervical cells collected in a simple OPD Procedures. This test can be done by itself or at the same time as the pap test.

The Pap (Papanicolaou)Test

The Pap test is a simple OPD procedure to collect cells from the cervix using a brush or spatula that can be looked up at the laboratory to find the presence of pre cancer or cancerous cells. The first step in finding cervical cancer is often an abnormal HPV or Pap test results. This will lead to further tests which can diagnose cervical cancer.

The most widely accepted screening protocols are those recommended by the American Cancer Society (ACS). The ACS in its latest 2020 recommendation published last month has slightly modified the previous recommendations.

The new recommendations for carcinoma cervix screening is enumerated below
a) Women age less than 25 years - No screening necessary
b) Women aged 25 – 65 years - Start at 25 years, HPV testing alone every 5 years (Preferred)
OR - Co testing every 5 years or Pap testalone every 3 years(less preferred)
c) Women aged more than 65 years - Discontinue screening if documented prior negative screening in the 10 years period before age 65.
d) After Hysterectomy - Individuals without a cervix and without a history of CIN 2 or more severe diagnosis in the past 25 years should not be screened.

Despite the existing National guidance the screening coverage is appalling low. Various other screening techniques such as Visual Inspection with Acetic acid (VIA), Visual Inspection with Lugol’s Iodine are also used in low income group countries. As a result of poor screening coverage the diagnosis is based mainly on opportunistic screening or after the onset of symptoms.

Improvements in the living standard and awareness among women through print and audio-visual media have resulted in a decline in the incidence of cervical cancer. The only way forward for a maximal reduction in the cervical cancer incidence and mortality seems to be routine HPV vaccination and population screening.