Human papilloma virus vaccines

Abstract

Human papilloma viruses (HPVs) infect the skin and mucosal epithelium of both men and women. There are about 100 types of HPVs, which are differentiated by the genetic sequence of the outer capsid protein L1. More than 30 types of HPVs are sexually transmitted. Most cases of carcinoma of the cervix are caused by HPV. Cervical cancer is one of the most common forms of cancer in women is the second biggest cause of female cancer mortality worldwide. The worldwide incidence of cervical carcinoma is 529,000 per year, and mortality is 275,000, of which an estimated 88% of deaths occur in developing countries. At least 20 million people worldwide are already chronically infected. Over 80% of cases of cervical carcinoma occurs in developing countries, with 25% estimated to occur in India. At least 50% of sexually active men and women encounter genital HPV at some time in their lives. Cervical cancer is ranked as the most frequent cancer in women in India. India has a population of approximately 366 million women above 15 y of age, who are at risk of developing cervical cancer. The current estimates indicate approximately 132,000 new cases diagnosed and 74,000 deaths annually in India, accounting for nearly one-third of the global cervical cancer deaths. HPV can be prevented by vaccination. Two types of HPV vaccines are available, as Gardasil and Cervarix, both of which are highly effective at preventing HPV infection. HPV vaccine is administered in a three-dose series administered by intramuscular injection, either in the deltoid muscle or in the antero-lateral thigh. The second and third doses should be administered 2 and 6 mo after the first dose respectively. The minimum interval between the first and second doses should be 4 weeks, between the second and third dose should be 12 weeks.

Keywords: :

• HPV
• cervical carcinoma
• wart
• death
• vaccines

Human Papilloma Virus Vaccines: Need to be Introduced in India

Human papilloma viruses (HPVs) are a group of viruses that infect the skin and mucous membranes of men and women. HPV has its name because certain HPV types can cause warts, known medically as papillomas. HPVs are small, double-stranded DNA viruses that infect the epithelial cells. There are about 100 types of HPVs, which are defined by the sequence of the outer capsid protein L1. HPV is one of the most common type of sexually transmitted disease (STD). More than 30 types of HPVs are sexually transmitted. Infection with HPV can result in cervical carcinoma, which is one of the most common forms of cancers in women and the second biggest cause of female cancer mortality worldwide. The annual worldwide incidence of cervical carcinoma is 529,000, with mortality of 275,000, of which an estimated 88% of deaths occur in developing countries. At least 20 million people are chronically infected with HPV. Over 80% of cases of cervical carcinoma occur in developing countries, with 25% estimated to occur in India.^1–3

At least 50% of sexually active men and women encounter genital HPV at some time in their lives, and at least 80% of women encounter genital HPV by age 50.⁴ Cervical cancer is ranked as the most frequent cancer in women in India. India has a population of approximately 366 million women > 15 y of age, who are at risk of developing cervical cancer. Approximately 132,000 new cases of cervical carcinoma are diagnosed with 74,000 deaths annually in India, accounting for nearly one-third of global cervical cancer deaths.⁵ Indian women face a 2.5% cumulative lifetime risk and 1.4% cumulative death risk from cervical cancer. At any given time, about 6.6% of women in the general population are estimated to harbor cervical HPV infection. HPV serotypes 16 and 18 account for nearly 77% of cervical cancer in India. Warts have been reported in 2–25% of STD clinic attendees in India.⁵

HPV can cause a number of medical conditions, including plantar warts, common warts, flat warts, genital warts, precancerous changes, cervical cancer and laryngeal papillomatosis. Some HPV types are referred to as “low-risk” viruses because infections rarely if ever develop into cancer. Low-risk HPV types cause no symptoms or may cause conditions such as genital warts, but not cervical cancer. Warts can form weeks, months, or even years after sexual contact with a person who has genital HPV. On the other hand, high-risk” HPVs are detected in 99% of cervical cancers. Sexually transmitted high-risk HPVs include types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 69, 73 and 82. All types of high risk HPVs cause cervical cancer except 59, 68 and 69. Type 16 is the cause of ~50% of cervical cancers worldwide and types 16 and 18 together account for about 70% of cervical cancers. The low-risk types 6 and 11 cause up to 90% of genital warts cases. Infection generally is transmitted by direct skin-to-skin contact. Genital HPV is spread through intercourse. HPV may also spread through touching something that has been contaminated with the virus and then touching the skin, although how often this occurs, if at all, is unknown.⁶

Most people infected with HPV never develop symptoms, including warts. If someone does develop symptoms, the exact type will depend on which HPV type is transmitted and the location of transmission. Most infected people are unaware that they are infected, but they can still transmit the virus to a sex partner. In rare cases, a pregnant woman can pass the virus to her baby during vaginal delivery. A baby that is exposed to HPV can develop warts in the throat or larynx, but this is rare. Most cases of HPV in women are suspected following an abnormal Pap smear. If a woman is age 30 or older, her healthcare provider also may perform an HPV DNA test,⁴ which detects most high-risk types of HPV and helps in screening for cervical cancer. If a woman is younger than 30 y old and has had a borderline-abnormal Pap test result, her healthcare provider also may perform an HPV DNA test. No HPV tests are available for men. HPV also may be diagnosed if warts are visible. Using condoms may reduce the risk of acquiring HPV infection that leads to genital warts or cancer, but they do not completely protect from infection.⁴

HPV can be prevented with a vaccine. Two types of HPV vaccines are available, Gardasil and Cervarix.⁷ Both vaccines protect against HPV-16 and HPV-18, which cause 70% of cervical cancers, 80% of anal cancers, 60% of vaginal cancers and 40% of vulvar cancers.⁸ Gardasil also protects against HPV-6 and HPV-11, which cause 90% of genital warts.⁹ Gardasil is a quadrivalent vaccine because it protects against four HPV types, while Cervarix is a bivalent vaccine because it targets two HPV types. Both vaccines have been shown to prevent potentially precancerous lesions of the cervix. Gardasil has been shown to prevent potential precursors to anal, vulvar, vaginal and penile cancers. HPV vaccines are expected to protect against HPV-induced cancers of these areas as well as HPV-induced oral cancers.^10–13

Schedule

HPV vaccine is administered in a three-dose series administered by intramuscular injection, either in the deltoid muscle or in the antero-lateral thigh. The second and third doses should be administered 2 and 6 mo after the first dose respectively. The minimum interval between the first and second doses should be 4 weeks, and between the second and third dose should be 12 weeks. Doses administered at an interval shorter than the minimum interval should not be counted as valid and should be repeated.¹⁴

HPV vaccine is given as a 3-dose series:¹⁴(1) first dose, 0 (date of commencement of first injection); (2) second dose, 2 mo after dose 1; (3) third dose, 6 mo after dose 1. Note, additional (booster) doses are not recommended.

If the HPV vaccine schedule is interrupted, the vaccine series does not need to be restarted. If the series is interrupted after the first dose, the second dose should be given as soon as possible, and the second and third doses should be separated by an interval of at least 12 weeks. If only the third dose is delayed, it should be administered as soon as possible. HPV vaccines can be given simultaneously with other vaccines such as Hepatitis B, TdaP and meningococcal polysaccharide or conjugate vaccines.¹⁵

The most common adverse reactions to HPV vaccine are local reactions like pain (mild to moderate) in 83%, swelling with erythema in 25% and systemic adverse effects such as fever in 4% of vaccinees. No serious vaccine-related adverse events have been reported. HPV vaccine is currently not licensed for use in subjects younger than 9 y or older than 26 y. HPV is contraindicated in people with a history of immediate hypersensitivity to yeast or to any of vaccine component. The vaccine may be administered in a sitting or lying down position, and the patient should be observed for 15 min post-vaccination for syncope. The vaccine is not recommended for use in pregnant women. Although HPV vaccine has not been causally associated with adverse outcomes of pregnancy, data are limited. Receiving HPV vaccine when pregnant is not a reason to consider terminating the pregnancy. If a woman is found to be pregnant after initiating the vaccination series, the remainder of the three-dose regimen should be delayed until after completion of the pregnancy. Lactating women and immunosuppressed female patients can receive the vaccine. The efficacy and the degree of immune response could be low in the latter group. People who are mildly ill when the shot is scheduled can still get the vaccine, but vaccination should be deferred in subjects with moderate or severe acute illnesses.^16,17

The available vaccines are safe and efficacious. Since protection is seen only when the vaccine is given before infection with HPV, the vaccine should preferably be given prior to sexual debut. The vaccine should preferably be introduced as a cervical cancer-preventing vaccine and not as a vaccine against a sexually transmitted infection (STI). The HPV vaccines are thus of public health importance. The Indian Association of Pediatrics in India recommends HPV vaccine to all females.